Progenitor cells from which all blood cells derive.
Transfer of HEMATOPOIETIC STEM CELLS from BONE MARROW or BLOOD between individuals within the same species (TRANSPLANTATION, HOMOLOGOUS) or transfer within the same individual (TRANSPLANTATION, AUTOLOGOUS). Hematopoietic stem cell transplantation has been used as an alternative to BONE MARROW TRANSPLANTATION in the treatment of a variety of neoplasms.
Relatively undifferentiated cells that retain the ability to divide and proliferate throughout postnatal life to provide progenitor cells that can differentiate into specialized cells.
The development and formation of various types of BLOOD CELLS. Hematopoiesis can take place in the BONE MARROW (medullary) or outside the bone marrow (HEMATOPOIESIS, EXTRAMEDULLARY).
The transfer of STEM CELLS from one individual to another within the same species (TRANSPLANTATION, HOMOLOGOUS) or between species (XENOTRANSPLANTATION), or transfer within the same individual (TRANSPLANTATION, AUTOLOGOUS). The source and location of the stem cells determines their potency or pluripotency to differentiate into various cell types.
A particular zone of tissue composed of a specialized microenvironment where stem cells are retained in a undifferentiated, self-renewable state.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
The release of stem cells from the bone marrow into the peripheral blood circulation for the purpose of leukapheresis, prior to stem cell transplantation. Hematopoietic growth factors or chemotherapeutic agents often are used to stimulate the mobilization.
Transplantation between individuals of the same species. Usually refers to genetically disparate individuals in contradistinction to isogeneic transplantation for genetically identical individuals.
The developmental history of specific differentiated cell types as traced back to the original STEM CELLS in the embryo.
Glycoproteins found on immature hematopoietic cells and endothelial cells. They are the only molecules to date whose expression within the blood system is restricted to a small number of progenitor cells in the bone marrow.
Cells with high proliferative and self renewal capacities derived from adults.
Cells derived from the BLASTOCYST INNER CELL MASS which forms before implantation in the uterine wall. They retain the ability to divide, proliferate and provide progenitor cells that can differentiate into specialized cells.
Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells.
A cytologic technique for measuring the functional capacity of stem cells by assaying their activity.
A hematopoietic growth factor and the ligand of the cell surface c-kit protein (PROTO-ONCOGENE PROTEINS C-KIT). It is expressed during embryogenesis and is a growth factor for a number of cell types including the MAST CELLS and the MELANOCYTES in addition to the HEMATOPOIETIC STEM CELLS.
Cells that can give rise to cells of the three different GERM LAYERS.
Specialized stem cells that are committed to give rise to cells that have a particular function; examples are MYOBLASTS; MYELOID PROGENITOR CELLS; and skin stem cells. (Stem Cells: A Primer [Internet]. Bethesda (MD): National Institutes of Health (US); 2000 May [cited 2002 Apr 5]. Available from:
The clinical entity characterized by anorexia, diarrhea, loss of hair, leukopenia, thrombocytopenia, growth retardation, and eventual death brought about by the GRAFT VS HOST REACTION.
Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.
Preparative treatment of transplant recipient with various conditioning regimens including radiation, immune sera, chemotherapy, and/or immunosuppressive agents, prior to transplantation. Transplantation conditioning is very common before bone marrow transplantation.
The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells.
Blood of the fetus. Exchange of nutrients and waste between the fetal and maternal blood occurs via the PLACENTA. The cord blood is blood contained in the umbilical vessels (UMBILICAL CORD) at the time of delivery.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
The transference of BONE MARROW from one human or animal to another for a variety of purposes including HEMATOPOIETIC STEM CELL TRANSPLANTATION or MESENCHYMAL STEM CELL TRANSPLANTATION.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
Transplantation of an individual's own tissue from one site to another site.
The blood-making organs and tissues, principally the bone marrow and lymph nodes.
Neoplasms located in the blood and blood-forming tissue (the bone marrow and lymphatic tissue). The commonest forms are the various types of LEUKEMIA, of LYMPHOMA, and of the progressive, life-threatening forms of the MYELODYSPLASTIC SYNDROMES.
One of a pair of excretory organs (mesonephroi) which grows caudally to the first pair (PRONEPHROI) during development. Mesonephroi are the permanent kidneys in adult amphibians and fish. In higher vertebrates, proneprhoi and most of mesonephroi degenerate with the appearance of metanephroi. The remaining ducts become WOLFFIAN DUCTS.
Cells from adult organisms that have been reprogrammed into a pluripotential state similar to that of EMBRYONIC STEM CELLS.
Bone-marrow-derived, non-hematopoietic cells that support HEMATOPOETIC STEM CELLS. They have also been isolated from other organs and tissues such as UMBILICAL CORD BLOOD, umbilical vein subendothelium, and WHARTON JELLY. These cells are considered to be a source of multipotent stem cells because they include subpopulations of mesenchymal stem cells.
Self-renewing cells that generate the main phenotypes of the nervous system in both the embryo and adult. Neural stem cells are precursors to both NEURONS and NEUROGLIA.
Transfer of MESENCHYMAL STEM CELLS between individuals within the same species (TRANSPLANTATION, HOMOLOGOUS) or transfer within the same individual (TRANSPLANTATION, AUTOLOGOUS).
Mice homozygous for the mutant autosomal recessive gene "scid" which is located on the centromeric end of chromosome 16. These mice lack mature, functional lymphocytes and are thus highly susceptible to lethal opportunistic infections if not chronically treated with antibiotics. The lack of B- and T-cell immunity resembles severe combined immunodeficiency (SCID) syndrome in human infants. SCID mice are useful as animal models since they are receptive to implantation of a human immune system producing SCID-human (SCID-hu) hematochimeric mice.
Cells derived from a FETUS that retain the ability to divide, proliferate and provide progenitor cells that can differentiate into specialized cells.
An organism that, as a result of transplantation of donor tissue or cells, consists of two or more cell lines descended from at least two zygotes. This state may result in the induction of donor-specific TRANSPLANTATION TOLERANCE.
A protein-tyrosine kinase receptor that is specific for STEM CELL FACTOR. This interaction is crucial for the development of hematopoietic, gonadal, and pigment stem cells. Genetic mutations that disrupt the expression of PROTO-ONCOGENE PROTEINS C-KIT are associated with PIEBALDISM, while overexpression or constitutive activation of the c-kit protein-tyrosine kinase is associated with tumorigenesis.
Transplantation of STEM CELLS collected from the fetal blood remaining in the UMBILICAL CORD and the PLACENTA after delivery. Included are the HEMATOPOIETIC STEM CELLS.
A strain of non-obese diabetic mice developed in Japan that has been widely studied as a model for T-cell-dependent autoimmune insulin-dependent diabetes mellitus in which insulitis is a major histopathologic feature, and in which genetic susceptibility is strongly MHC-linked.
Irradiation of the whole body with ionizing or non-ionizing radiation. It is applicable to humans or animals but not to microorganisms.
The survival of a graft in a host, the factors responsible for the survival and the changes occurring within the graft during growth in the host.
A genus of the family RETROVIRIDAE consisting of non-oncogenic retroviruses that produce multi-organ diseases characterized by long incubation periods and persistent infection. Lentiviruses are unique in that they contain open reading frames (ORFs) between the pol and env genes and in the 3' env region. Five serogroups are recognized, reflecting the mammalian hosts with which they are associated. HIV-1 is the type species.
Methods for maintaining or growing CELLS in vitro.
The transfer of bacterial DNA by phages from an infected bacterium to another bacterium. This also refers to the transfer of genes into eukaryotic cells by viruses. This naturally occurring process is routinely employed as a GENE TRANSFER TECHNIQUE.
The occurrence in an individual of two or more cell populations of different chromosomal constitutions, derived from different individuals. This contrasts with MOSAICISM in which the different cell populations are derived from a single individual.
A progressive, malignant disease of the blood-forming organs, characterized by distorted proliferation and development of leukocytes and their precursors in the blood and bone marrow. Leukemias were originally termed acute or chronic based on life expectancy but now are classified according to cellular maturity. Acute leukemias consist of predominately immature cells; chronic leukemias are composed of more mature cells. (From The Merck Manual, 2006)
Stem cells derived from HEMATOPOIETIC STEM CELLS. Derived from these myeloid progenitor cells are the MEGAKARYOCYTES; ERYTHROID CELLS; MYELOID CELLS; and some DENDRITIC CELLS.
A glycoprotein of MW 25 kDa containing internal disulfide bonds. It induces the survival, proliferation, and differentiation of neutrophilic granulocyte precursor cells and functionally activates mature blood neutrophils. Among the family of colony-stimulating factors, G-CSF is the most potent inducer of terminal differentiation to granulocytes and macrophages of leukemic myeloid cell lines.
Transplantation of stem cells collected from the peripheral blood. It is a less invasive alternative to direct marrow harvesting of hematopoietic stem cells. Enrichment of stem cells in peripheral blood can be achieved by inducing mobilization of stem cells from the BONE MARROW.
Individuals supplying living tissue, organs, cells, blood or blood components for transfer or transplantation to histocompatible recipients.
Family of RNA viruses that infects birds and mammals and encodes the enzyme reverse transcriptase. The family contains seven genera: DELTARETROVIRUS; LENTIVIRUS; RETROVIRUSES TYPE B, MAMMALIAN; ALPHARETROVIRUS; GAMMARETROVIRUS; RETROVIRUSES TYPE D; and SPUMAVIRUS. A key feature of retrovirus biology is the synthesis of a DNA copy of the genome which is integrated into cellular DNA. After integration it is sometimes not expressed but maintained in a latent state (PROVIRUSES).
Formation of LYMPHOCYTES and PLASMA CELLS from the lymphoid stem cells which develop from the pluripotent HEMATOPOIETIC STEM CELLS in the BONE MARROW. These lymphoid stem cells differentiate into T-LYMPHOCYTES; B-LYMPHOCYTES; PLASMA CELLS; or NK-cells (KILLER CELLS, NATURAL) depending on the organ or tissues (LYMPHOID TISSUE) to which they migrate.
DNA molecules capable of autonomous replication within a host cell and into which other DNA sequences can be inserted and thus amplified. Many are derived from PLASMIDS; BACTERIOPHAGES; or VIRUSES. They are used for transporting foreign genes into recipient cells. Genetic vectors possess a functional replicator site and contain GENETIC MARKERS to facilitate their selective recognition.
Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
The formation and development of blood cells outside the BONE MARROW, as in the SPLEEN; LIVER; or LYMPH NODES.
Highly proliferative, self-renewing, and colony-forming stem cells which give rise to NEOPLASMS.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
An organism whose body contains cell populations of different genotypes as a result of the TRANSPLANTATION of donor cells after sufficient ionizing radiation to destroy the mature recipient's cells which would otherwise reject the donor cells.
Elements of limited time intervals, contributing to particular results or situations.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
Connective tissue cells of an organ found in the loose connective tissue. These are most often associated with the uterine mucosa and the ovary as well as the hematopoietic system and elsewhere.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
A bifunctional enzyme that catalyzes the synthesis and HYDROLYSIS of CYCLIC ADP-RIBOSE (cADPR) from NAD+ to ADP-RIBOSE. It is a cell surface molecule which is predominantly expressed on LYMPHOID CELLS and MYELOID CELLS.
A group of lymphocyte surface antigens located on mouse LYMPHOCYTES. Specific Ly antigens are useful markers for distinguishing subpopulations of lymphocytes.
A humoral factor that stimulates the production of thrombocytes (BLOOD PLATELETS). Thrombopoietin stimulates the proliferation of bone marrow MEGAKARYOCYTES and their release of blood platelets. The process is called THROMBOPOIESIS.
The physiological renewal, repair, or replacement of tissue.
An alkylating agent having a selective immunosuppressive effect on BONE MARROW. It has been used in the palliative treatment of chronic myeloid leukemia (MYELOID LEUKEMIA, CHRONIC), but although symptomatic relief is provided, no permanent remission is brought about. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), busulfan is listed as a known carcinogen.
The entity of a developing mammal (MAMMALS), generally from the cleavage of a ZYGOTE to the end of embryonic differentiation of basic structures. For the human embryo, this represents the first two months of intrauterine development preceding the stages of the FETUS.
Techniques and strategies which include the use of coding sequences and other conventional or radical means to transform or modify cells for the purpose of treating or reversing disease conditions.
Identification of the major histocompatibility antigens of transplant DONORS and potential recipients, usually by serological tests. Donor and recipient pairs should be of identical ABO blood group, and in addition should be matched as closely as possible for HISTOCOMPATIBILITY ANTIGENS in order to minimize the likelihood of allograft rejection. (King, Dictionary of Genetics, 4th ed)
Experimentation on STEM CELLS and on the use of stem cells.
The degree of antigenic similarity between the tissues of different individuals, which determines the acceptance or rejection of allografts.
A technique of culturing mixed cell types in vitro to allow their synergistic or antagonistic interactions, such as on CELL DIFFERENTIATION or APOPTOSIS. Coculture can be of different types of cells, tissues, or organs from normal or disease states.
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
A group of differentiation surface antigens, among the first to be discovered on thymocytes and T-lymphocytes. Originally identified in the mouse, they are also found in other species including humans, and are expressed on brain neurons and other cells.
Disorders of the blood and blood forming tissues.
Parts of plants that usually grow vertically upwards towards the light and support the leaves, buds, and reproductive structures. (From Concise Dictionary of Biology, 1990)
Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, and practicability of these interventions in individual cases or series.
The classes of BONE MARROW-derived blood cells in the monocytic series (MONOCYTES and their precursors) and granulocytic series (GRANULOCYTES and their precursors).
The first of four extra-embryonic membranes to form during EMBRYOGENESIS. In REPTILES and BIRDS, it arises from endoderm and mesoderm to incorporate the EGG YOLK into the DIGESTIVE TRACT for nourishing the embryo. In placental MAMMALS, its nutritional function is vestigial; however, it is the source of INTESTINAL MUCOSA; BLOOD CELLS; and GERM CELLS. It is sometimes called the vitelline sac, which should not be confused with the VITELLINE MEMBRANE of the egg.
A CXC chemokine that is chemotactic for T-LYMPHOCYTES and MONOCYTES. It has specificity for CXCR4 RECEPTORS. Two isoforms of CXCL12 are produced by alternative mRNA splicing.
Protein analogs and derivatives of the Aequorea victoria green fluorescent protein that emit light (FLUORESCENCE) when excited with ULTRAVIOLET RAYS. They are used in REPORTER GENES in doing GENETIC TECHNIQUES. Numerous mutants have been made to emit other colors or be sensitive to pH.
Formation of MYELOID CELLS from the pluripotent HEMATOPOIETIC STEM CELLS in the BONE MARROW via MYELOID STEM CELLS. Myelopoiesis generally refers to the production of leukocytes in blood, such as MONOCYTES and GRANULOCYTES. This process also produces precursor cells for MACROPHAGE and DENDRITIC CELLS found in the lymphoid tissue.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
The number of CELLS of a specific kind, usually measured per unit volume or area of sample.
Group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. It is inherited as an X-linked or autosomal recessive defect. Mutations occurring in many different genes cause human Severe Combined Immunodeficiency (SCID).
Mouse strains constructed to possess identical genotypes except for a difference at a single gene locus.
The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.
The cells found in the body fluid circulating throughout the CARDIOVASCULAR SYSTEM.
Clonal hematopoietic stem cell disorders characterized by dysplasia in one or more hematopoietic cell lineages. They predominantly affect patients over 60, are considered preleukemic conditions, and have high probability of transformation into ACUTE MYELOID LEUKEMIA.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action during the developmental stages of an organism.
The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.
Clonal expansion of myeloid blasts in bone marrow, blood, and other tissue. Myeloid leukemias develop from changes in cells that normally produce NEUTROPHILS; BASOPHILS; EOSINOPHILS; and MONOCYTES.
The gamete-producing glands, OVARY or TESTIS.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
Transplantation between animals of different species.
An essential GATA transcription factor that is expressed primarily in HEMATOPOIETIC STEM CELLS.
Process of classifying cells of the immune system based on structural and functional differences. The process is commonly used to analyze and sort T-lymphocytes into subsets based on CD antigens by the technique of flow cytometry.
A transcription factor that dimerizes with the cofactor CORE BINDING FACTOR BETA SUBUNIT to form core binding factor. It contains a highly conserved DNA-binding domain known as the runt domain. Runx1 is frequently mutated in human LEUKEMIAS.
Immunological rejection of leukemia cells following bone marrow transplantation.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
Agents that destroy bone marrow activity. They are used to prepare patients for BONE MARROW TRANSPLANTATION or STEM CELL TRANSPLANTATION.
Leukocytes with abundant granules in the cytoplasm. They are divided into three groups according to the staining properties of the granules: neutrophilic, eosinophilic, and basophilic. Mature granulocytes are the NEUTROPHILS; EOSINOPHILS; and BASOPHILS.
The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.
High-molecular weight glycoproteins uniquely expressed on the surface of LEUKOCYTES and their hemopoietic progenitors. They contain a cytoplasmic protein tyrosine phosphatase activity which plays a role in intracellular signaling from the CELL SURFACE RECEPTORS. The CD45 antigens occur as multiple isoforms that result from alternative mRNA splicing and differential usage of three exons.
Established cell cultures that have the potential to propagate indefinitely.
The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.
These growth factors comprise a family of hematopoietic regulators with biological specificities defined by their ability to support proliferation and differentiation of blood cells of different lineages. ERYTHROPOIETIN and the COLONY-STIMULATING FACTORS belong to this family. Some of these factors have been studied and used in the treatment of chemotherapy-induced neutropenia, myelodysplastic syndromes, and bone marrow failure syndromes.
An interleukin receptor subunit that was originally discovered as a component of the INTERLEUKIN 2 RECEPTOR. It was subsequently found to be a component of several other receptors including the INTERLEUKIN 4 RECEPTOR, the INTERLEUKIN 7 RECEPTOR, the INTERLEUKIN-9 RECEPTOR, the INTERLEUKIN-15 RECEPTOR, and the INTERLEUKIN-21 RECEPTOR. Mutations in the gene for the interleukin receptor common gamma chain have been associated with X-LINKED COMBINED IMMUNODEFICIENCY DISEASES.
The number of LEUKOCYTES and ERYTHROCYTES per unit volume in a sample of venous BLOOD. A complete blood count (CBC) also includes measurement of the HEMOGLOBIN; HEMATOCRIT; and ERYTHROCYTE INDICES.
Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.
Proteins encoded by homeobox genes (GENES, HOMEOBOX) that exhibit structural similarity to certain prokaryotic and eukaryotic DNA-binding proteins. Homeodomain proteins are involved in the control of gene expression during morphogenesis and development (GENE EXPRESSION REGULATION, DEVELOPMENTAL).
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc.
Clonal hematopoetic disorder caused by an acquired genetic defect in PLURIPOTENT STEM CELLS. It starts in MYELOID CELLS of the bone marrow, invades the blood and then other organs. The condition progresses from a stable, more indolent, chronic phase (LEUKEMIA, MYELOID, CHRONIC PHASE) lasting up to 7 years, to an advanced phase composed of an accelerated phase (LEUKEMIA, MYELOID, ACCELERATED PHASE) and BLAST CRISIS.
The unborn young of a viviparous mammal, in the postembryonic period, after the major structures have been outlined. In humans, the unborn young from the end of the eighth week after CONCEPTION until BIRTH, as distinguished from the earlier EMBRYO, MAMMALIAN.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
Very large BONE MARROW CELLS which release mature BLOOD PLATELETS.
Studies used to test etiologic hypotheses in which inferences about an exposure to putative causal factors are derived from data relating to characteristics of persons under study or to events or experiences in their past. The essential feature is that some of the persons under study have the disease or outcome of interest and their characteristics are compared with those of unaffected persons.
Local surroundings with which cells interact by processing various chemical and physical signals, and by contributing their own effects to this environment.
A group of genetically identical cells all descended from a single common ancestral cell by mitosis in eukaryotes or by binary fission in prokaryotes. Clone cells also include populations of recombinant DNA molecules all carrying the same inserted sequence. (From King & Stansfield, Dictionary of Genetics, 4th ed)
Cell surface receptors that are specific for THROMBOPOIETIN. They signal through interaction with JANUS KINASES such as JANUS KINASE 2.
CXCR receptors with specificity for CXCL12 CHEMOKINE. The receptors may play a role in HEMATOPOIESIS regulation and can also function as coreceptors for the HUMAN IMMUNODEFICIENCY VIRUS.
Transference of cells within an individual, between individuals of the same species, or between individuals of different species.
The decrease in the cell's ability to proliferate with the passing of time. Each cell is programmed for a certain number of cell divisions and at the end of that time proliferation halts. The cell enters a quiescent state after which it experiences CELL DEATH via the process of APOPTOSIS.
A multilineage cell growth factor secreted by LYMPHOCYTES; EPITHELIAL CELLS; and ASTROCYTES which stimulates clonal proliferation and differentiation of various types of blood and tissue cells.
Therapies that involve the TRANSPLANTATION of CELLS or TISSUES developed for the purpose of restoring the function of diseased or dysfunctional cells or tissues.
The introduction of functional (usually cloned) GENES into cells. A variety of techniques and naturally occurring processes are used for the gene transfer such as cell hybridization, LIPOSOMES or microcell-mediated gene transfer, ELECTROPORATION, chromosome-mediated gene transfer, TRANSFECTION, and GENETIC TRANSDUCTION. Gene transfer may result in genetically transformed cells and individual organisms.
Conditions which cause proliferation of hemopoietically active tissue or of tissue which has embryonic hemopoietic potential. They all involve dysregulation of multipotent MYELOID PROGENITOR CELLS, most often caused by a mutation in the JAK2 PROTEIN TYROSINE KINASE.
A membrane-bound or cytosolic enzyme that catalyzes the synthesis of CYCLIC ADP-RIBOSE (cADPR) from nicotinamide adenine dinucleotide (NAD). This enzyme generally catalyzes the hydrolysis of cADPR to ADP-RIBOSE, as well, and sometimes the synthesis of cyclic ADP-ribose 2' phosphate (2'-P-cADPR) from NADP.
Mice bearing mutant genes which are phenotypically expressed in the animals.
A field of medicine concerned with developing and using strategies aimed at repair or replacement of damaged, diseased, or metabolically deficient organs, tissues, and cells via TISSUE ENGINEERING; CELL TRANSPLANTATION; and ARTIFICIAL ORGANS and BIOARTIFICIAL ORGANS and tissues.
An encapsulated lymphatic organ through which venous blood filters.
Ring compounds having atoms other than carbon in their nuclei. (Grant & Hackh's Chemical Dictionary, 5th ed)
Single cells that have the potential to form an entire organism. They have the capacity to specialize into extraembryonic membranes and tissues, the embryo, and all postembryonic tissues and organs. (Stem Cells: A Primer [Internet]. Bethesda (MD): National Institutes of Health (US); 2000 May [cited 2002 Apr 5]. Available from:
Antigens determined by leukocyte loci found on chromosome 6, the major histocompatibility loci in humans. They are polypeptides or glycoproteins found on most nucleated cells and platelets, determine tissue types for transplantation, and are associated with certain diseases.
Transplantation between genetically identical individuals, i.e., members of the same species with identical histocompatibility antigens, such as monozygotic twins, members of the same inbred strain, or members of a hybrid population produced by crossing certain inbred strains.
A single, unpaired primary lymphoid organ situated in the MEDIASTINUM, extending superiorly into the neck to the lower edge of the THYROID GLAND and inferiorly to the fourth costal cartilage. It is necessary for normal development of immunologic function early in life. By puberty, it begins to involute and much of the tissue is replaced by fat.
The return of a sign, symptom, or disease after a remission.
Persons or animals having at least one parent in common. (American College Dictionary, 3d ed)
Bone-forming cells which secrete an EXTRACELLULAR MATRIX. HYDROXYAPATITE crystals are then deposited into the matrix to form bone.
The preparation of leukocyte concentrates with the return of red cells and leukocyte-poor plasma to the donor.
The cells in the erythroid series derived from MYELOID PROGENITOR CELLS or from the bi-potential MEGAKARYOCYTE-ERYTHROID PROGENITOR CELLS which eventually give rise to mature RED BLOOD CELLS. The erythroid progenitor cells develop in two phases: erythroid burst-forming units (BFU-E) followed by erythroid colony-forming units (CFU-E); BFU-E differentiate into CFU-E on stimulation by ERYTHROPOIETIN, and then further differentiate into ERYTHROBLASTS when stimulated by other factors.
A form of anemia in which the bone marrow fails to produce adequate numbers of peripheral blood elements.
Antigens expressed primarily on the membranes of living cells during sequential stages of maturation and differentiation. As immunologic markers they have high organ and tissue specificity and are useful as probes in studies of normal cell development as well as neoplastic transformation.
The production of red blood cells (ERYTHROCYTES). In humans, erythrocytes are produced by the YOLK SAC in the first trimester; by the liver in the second trimester; by the BONE MARROW in the third trimester and after birth. In normal individuals, the erythrocyte count in the peripheral blood remains relatively constant implying a balance between the rate of erythrocyte production and rate of destruction.
Liver disease that is caused by injuries to the ENDOTHELIAL CELLS of the vessels and subendothelial EDEMA, but not by THROMBOSIS. Extracellular matrix, rich in FIBRONECTINS, is usually deposited around the HEPATIC VEINS leading to venous outflow occlusion and sinusoidal obstruction.
An octamer transcription factor that is expressed primarily in totipotent embryonic STEM CELLS and GERM CELLS and is down-regulated during CELL DIFFERENTIATION.
A condition characterized by the recurrence of HEMOGLOBINURIA caused by intravascular HEMOLYSIS. In cases occurring upon cold exposure (paroxysmal cold hemoglobinuria), usually after infections, there is a circulating antibody which is also a cold hemolysin. In cases occurring during or after sleep (paroxysmal nocturnal hemoglobinuria), the clonal hematopoietic stem cells exhibit a global deficiency of cell membrane proteins.
An individual that contains cell populations derived from different zygotes.
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.
Platelet membrane glycoprotein IIb is an integrin alpha subunit that heterodimerizes with INTEGRIN BETA3 to form PLATELET GLYCOPROTEIN GPIIB-IIIA COMPLEX. It is synthesized as a single polypeptide chain which is then postranslationally cleaved and processed into two disulfide-linked subunits of approximately 18 and 110 kDa in size.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
Genes that are introduced into an organism using GENE TRANSFER TECHNIQUES.
A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.
A fluorescent probe with low toxicity which is a potent substrate for P-glycoprotein and the bacterial multidrug efflux transporter. It is used to assess mitochondrial bioenergetics in living cells and to measure the efflux activity of P-glycoprotein in both normal and malignant cells. (Leukemia 1997;11(7):1124-30)
Tissues, cells, or organs transplanted between genetically different individuals of the same species.
A family of conserved cell surface receptors that contain EPIDERMAL GROWTH FACTOR repeats in their extracellular domain and ANKYRIN repeats in their cytoplasmic domains. The cytoplasmic domain of notch receptors is released upon ligand binding and translocates to the CELL NUCLEUS where it acts as transcription factor.
Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation.
Providers of tissues for transplant to non-related individuals.
In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.
Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.
Form of leukemia characterized by an uncontrolled proliferation of the myeloid lineage and their precursors (MYELOID PROGENITOR CELLS) in the bone marrow and other sites.
Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
Congenital disorder affecting all bone marrow elements, resulting in ANEMIA; LEUKOPENIA; and THROMBOPENIA, and associated with cardiac, renal, and limb malformations as well as dermal pigmentary changes. Spontaneous CHROMOSOME BREAKAGE is a feature of this disease along with predisposition to LEUKEMIA. There are at least 7 complementation groups in Fanconi anemia: FANCA, FANCB, FANCC, FANCD1, FANCD2, FANCE, FANCF, FANCG, and FANCL. (from Online Mendelian Inheritance in Man,, August 20, 2004)
Bipotential angio-hematopoietic stem cells that give rise to both HEMATOPOIETIC STEM CELLS and ENDOTHELIAL CELLS.
A nucleoside antibiotic isolated from Streptomyces antibioticus. It has some antineoplastic properties and has broad spectrum activity against DNA viruses in cell cultures and significant antiviral activity against infections caused by a variety of viruses such as the herpes viruses, the VACCINIA VIRUS and varicella zoster virus.
A malignancy of mature PLASMA CELLS engaging in monoclonal immunoglobulin production. It is characterized by hyperglobulinemia, excess Bence-Jones proteins (free monoclonal IMMUNOGLOBULIN LIGHT CHAINS) in the urine, skeletal destruction, bone pain, and fractures. Other features include ANEMIA; HYPERCALCEMIA; and RENAL INSUFFICIENCY.
The series of cells in the red blood cell lineage at various stages of differentiation.
The treatment of a disease or condition by several different means simultaneously or sequentially. Chemoimmunotherapy, RADIOIMMUNOTHERAPY, chemoradiotherapy, cryochemotherapy, and SALVAGE THERAPY are seen most frequently, but their combinations with each other and surgery are also used.
The proportion of survivors in a group, e.g., of patients, studied and followed over a period, or the proportion of persons in a specified group alive at the beginning of a time interval who survive to the end of the interval. It is often studied using life table methods.
Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the LIVER to form the active aldophosphamide. It has been used in the treatment of LYMPHOMA and LEUKEMIA. Its side effect, ALOPECIA, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer.
Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of INTERLEUKINS and other CYTOKINES are emerging.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
A cell-separation technique where magnetizable microspheres or beads are first coated with monoclonal antibody, allowed to search and bind to target cells, and are then selectively removed when passed through a magnetic field. Among other applications, the technique is commonly used to remove tumor cells from the marrow (BONE MARROW PURGING) of patients who are to undergo autologous bone marrow transplantation.
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.
Infection with CYTOMEGALOVIRUS, characterized by enlarged cells bearing intranuclear inclusions. Infection may be in almost any organ, but the salivary glands are the most common site in children, as are the lungs in adults.
Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.
A notch receptor that interacts with a variety of ligands and regulates SIGNAL TRANSDUCTION PATHWAYS for multiple cellular processes. It is widely expressed during EMBRYOGENESIS and is essential for EMBRYONIC DEVELOPMENT.
A human or animal whose immunologic mechanism is deficient because of an immunodeficiency disorder or other disease or as the result of the administration of immunosuppressive drugs or radiation.
An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression.
Transference of fetal tissue between individuals of the same species or between individuals of different species.
The process of generating thrombocytes (BLOOD PLATELETS) from the pluripotent HEMATOPOIETIC STEM CELLS in the BONE MARROW via the MEGAKARYOCYTES. The humoral factor with thrombopoiesis-stimulating activity is designated THROMBOPOIETIN.
Disease having a short and relatively severe course.
A de novo myeloproliferation arising from an abnormal stem cell. It is characterized by the replacement of bone marrow by fibrous tissue, a process that is mediated by CYTOKINES arising from the abnormal clone.
Therapeutic act or process that initiates a response to a complete or partial remission level.
Hybridization of a nucleic acid sample to a very large set of OLIGONUCLEOTIDE PROBES, which have been attached individually in columns and rows to a solid support, to determine a BASE SEQUENCE, or to detect variations in a gene sequence, GENE EXPRESSION, or for GENE MAPPING.
Immunological rejection of tumor tissue/cells following bone marrow transplantation.
A family of DNA-binding transcription factors that contain a basic HELIX-LOOP-HELIX MOTIF.
Methods used for detecting the amplified DNA products from the polymerase chain reaction as they accumulate instead of at the end of the reaction.
The transfer of lymphocytes from a donor to a recipient or reinfusion to the donor.
A neoplasm characterized by abnormalities of the lymphoid cell precursors leading to excessive lymphoblasts in the marrow and other organs. It is the most common cancer in children and accounts for the vast majority of all childhood leukemias.
A general term for the complex phenomena involved in allo- and xenograft rejection by a host and graft vs host reaction. Although the reactions involved in transplantation immunology are primarily thymus-dependent phenomena of cellular immunity, humoral factors also play a part in late rejection.

ETO-2, a new member of the ETO-family of nuclear proteins. (1/11748)

The t(8;21) is associated with 12-15% of acute myelogenous leukemias of the M2 subtype. The translocation results in the fusion of two genes, AML1 (CBFA2) on chromosome 21 and ETO (MTG8) on chromosome 8. AML1 encodes a DNA binding factor; the ETO protein product is less well characterized, but is thought to be a transcription factor. Here we describe the isolation and characterization of ETO-2, a murine cDNA that encodes a new member of the ETO family of proteins. ETO-2 is 75% identical to murine ETO and shares very high sequence identities over four regions of the protein with ETO (domain I-III and zinc-finger). Northern analysis identifies ETO-2 transcripts in many of the murine tissues analysed and in the developing mouse embryo. ETO-2 is also expressed in myeloid and erythroid cell lines. We confirmed the nuclear localization of ETO-2 and demonstrated that domain III and the zinc-finger region are not required for nuclear localization. We further showed that a region within ETO, containing domain II, mediates dimerization among family members. This region is conserved in the oncoprotein AML-1/ETO. The recent identification of another ETO-like protein, myeloid translocation gene-related protein 1, together with the data presented here, demonstrates that at least three ETO proteins exist with the potential to form dimers in the cell nucleus.  (+info)

Establishment of an inducible expression system of chimeric MLL-LTG9 protein and inhibition of Hox a7, Hox b7 and Hox c9 expression by MLL-LTG9 in 32Dcl3 cells. (2/11748)

The MLL (HRX/ALL-1 gene is frequently disrupted in infantile leukemias and therapy-related leukemias and fused to various translocation partner genes. We previously showed that chimeric MLL proteins localize in the nuclei in a fashion similar to that of MLL protein even if the partner gene encodes a cytoplasmic protein and indicated the importance of the N-terminal portion of MLL common to various MLL translocations. This time we established an inducible expression system for chimeric MLL-LTG9 and truncated N-terminal MLL proteins (MLL-Zf(-)) in 32Dcl3 cells. By utilizing this system, we were able to show inhibition of Hox a7, Hox b7 and Hox c9 genes' expression by induced MLL-LTG9 and MLL-Zf(-). Up-regulation of Hox a7, Hox b7 and Hox c9 was observed when 32Dcl3 cells were cultured with granulocyte colony stimulating factor (G-CSF) in place of interleukin 3 and induction of MLL-LTG9 and MLL-Zf(-) was shown to suppress this upregulation. At the same time, expression of two mammalian Polycomb group genes, M33 and mel-18, which both reportedly affect Hox genes' expression, was not inhibited by MLL-LTG9 and MLL-Zf(-) induction. These results indicate that MLL has an important effect on the expression of at least some Hox genes in hematopoietic cells and suggest that inhibition of the proper expression of Hox genes by chimeric MLL proteins may dysregulate hematopoietic cell differentiation and proliferation, which then can lead to leukemogenesis.  (+info)

Prolonged eosinophil accumulation in allergic lung interstitium of ICAM-2 deficient mice results in extended hyperresponsiveness. (3/11748)

ICAM-2-deficient mice exhibit prolonged accumulation of eosinophils in lung interstitium concomitant with a delayed increase in eosinophil numbers in the airway lumen during the development of allergic lung inflammation. The ICAM-2-dependent increased and prolonged accumulation of eosinophils in lung interstitium results in prolonged, heightened airway hyperresponsiveness. These findings reveal an essential role for ICAM-2 in the development of the inflammatory and respiratory components of allergic lung disease. This phenotype is caused by the lack of ICAM-2 expression on non-hematopoietic cells. ICAM-2 deficiency on endothelial cells causes reduced eosinophil transmigration in vitro. ICAM-2 is not essential for lymphocyte homing or the development of leukocytes, with the exception of megakaryocyte progenitors, which are significantly reduced.  (+info)

Enhanced myeloid progenitor cell cycling and apoptosis in mice lacking the chemokine receptor, CCR2. (4/11748)

Chemokines regulate hematopoiesis in part by influencing the proliferative status of myeloid progenitor cells (MPC). Human MCP-1/murine JE, a myelosuppressive chemokine, specifically binds C-C chemokine receptor 2 (CCR2). Transgenic mice containing a targeted disruption in CCR2 that prevents expression of CCR2 mRNA and protein and have MPC that are insensitive to inhibition by MCP-1 and JE in vitro were assessed for potential abnormalities in growth of bone marrow (BM) and spleen MPC. MPC in both unseparated and c-kit+lin- populations of BM from CCR2-deficient (-/-) mice were in a greatly increased proliferation state compared with CCR2 littermate control (+/+) mice, an effect not apparent with progenitors from spleens of CCR2 (-/-) mice. Increased cycling status of CCR2 (-/-) BM MPC did not result in increased numbers of nucleated cells or MPC in BM or spleens of CCR2 (-/-) mice. Possible reasons for this apparent discrepancy were highlighted by flow cytometric analysis of c-kit+lin- BM cells and colony formation by MPC subjected to delayed addition of growth factors. The c-kit+lin- population of BM cells from CCR2 (-/-) mice had a significantly higher percentage of apoptotic cells than those from CCR2 (+/+) BM. However, elevated apoptosis was not associated with decreased numbers of c-kit+lin- cells. The increased percentage of apoptotic c-kit+lin- cells was due to elevated apoptosis within the c-kitdimlin-, but not the c-kitbrightlin-, subpopulations of cells. Consistent with enhanced apoptosis of phenotypically defined cells, MPC from CCR2 (-/-) BM and purified c-kit+lin- cells demonstrated decreased cell survival in vitro upon delayed addition of growth factors. The data suggest that signals received by CCR2 limit proliferation of progenitor cells in the BM, but also enhance survival of these cells.  (+info)

Autografting with philadelphia chromosome-negative mobilized hematopoietic progenitor cells in chronic myelogenous leukemia. (5/11748)

Intensive chemotherapy given in early chronic phase of chronic myelogenous leukemia (CML) has resulted in high numbers of circulating Philadelphia (Ph) chromosome-negative hematopoietic progenitor cells (HPC). We have autografted 30 consecutive patients with CML in chronic phase with HPC collected in this way to facilitate restoration of Ph-negative hematopoiesis in bone marrow after high-dose therapy. Hematopoietic recovery to greater than 0.5 x10(9)/L neutrophils and to greater than 25 x 10(9)/L platelets occurred in all patients, a median of 13 (range, 9 to 32) days and 16 (range, 6 to 106) days postautograft, respectively. Regenerating marrow cells were Ph-negative in 16 (53%) patients and greater than 66% Ph-negative in 10 (33%) patients. Twenty-eight patients are alive 6 to 76 months (median, 24 months) after autografting. Three patients have developed blast crisis from which 2 have died. Eight patients are in complete cytogenetic remission at a median of 20 (range, 6 to 44) months with a median ratio BCR-ABL/ABL of 0.002 (range, <0.001 to 0.01). Eight patients are in major cytogenetic remission at a median of 22 (range, 6 to 48) months. No patient died as a consequence of the treatment. All patients had some degree of stomatitis that was severe in 15 (50%) patients. Gastrointestinal and hepatic toxicities were observed in about one fourth of patients. Thus, autografting with Ph-negative mobilized HPC can result in prolonged restoration of Ph-negative hematopoiesis for some patients with CML; moreover, most autograft recipients report normal or near normal activity levels, suggesting that this procedure need not to be associated either with prolonged convalescence or with chronic debility.  (+info)

H-Ras is involved in the inside-out signaling pathway of interleukin-3-induced integrin activation. (6/11748)

The proto-oncogene product, p21(ras), has been implicated in the cellular mechanism of adhesion, although its precise role has been controversial. Numerous cytokines and growth-factors activate Ras, which is an important component of their growth-promoting signaling pathways. On the other hand, the role of Ras in cytokine-induced adhesion has not been elucidated. We therefore investigated the function of H-Ras in the inside-out signaling pathway of interleukin-3 (IL-3)-induced integrin activation in the murine Baf3 cell line after transfection of cells with either constitutively active, dominant-negative, or wild-type H-Ras cDNAs. Adhesion of Baf3 cells to fibronectin was induced by IL-3 in a dose-dependent manner via very late antigen-4 (VLA-4; alpha4beta1 integrins) and VLA-5 (alpha5beta1 integrins) activation. On the other hand, IL-4 did not induce the adhesion of Baf3 cells to fibronectin, although IL-4 did stimulate the cell proliferation of Baf3 cells. Constitutively active H-Ras-transfected Baf3 cells adhered to fibronectin without IL-3 stimulation through VLA-4 and VLA-5, whereas dominant-negative H-Ras-transfected Baf3 cells showed significantly less adhesion induced by IL-3 compared with wild-type and constitutively active H-Ras-transfected Baf3 cells. Anti-beta1 integrin antibody (clone; 9EG7), which is known to change integrin conformation and activate integrins, induced the adhesion of dominant-negative H-Ras-transfected Baf3 cells as much as the other types of H-Ras-transfected Baf3 cells. 8-Br-cAMP, Dibutyryl-cAMP, Ras-Raf-1 pathway inhibitors, and PD98059, a MAPK kinase inhibitor, suppressed proliferation and phosphorylation of MAPK detected by Western blotting with anti-phospho-MAPK antibody, but not adhesion of any type of H-Ras-transfected Baf3 cells, whereas U-73122, a phospholipase C (PLC) inhibitor, suppressed adhesion of these cells completely. These data indicate that H-Ras and PLC, but not Raf-1, MAPK kinase, or the MAPK pathway, are involved in the inside-out signaling pathway of IL-3-induced VLA-4 and VLA-5 activation in Baf3 cells.  (+info)

In vitro hematopoietic and endothelial cell development from cells expressing TEK receptor in murine aorta-gonad-mesonephros region. (7/11748)

Recent studies have shown that long-term repopulating hematopoietic stem cells (HSCs) first appear in the aorta-gonad-mesonephros (AGM) region. Our immunohistochemistry study showed that TEK+ cells existed in the AGM region. Approximately 5% of AGM cells were TEK+, and most of these were CD34(+) and c-Kit+. We then established a coculture system of AGM cells using a stromal cell line, OP9, which is deficient in macrophage colony-stimulating factor (M-CSF). With this system, we showed that AGM cells at 10.5 days postcoitum (dpc) differentiated and proliferated into both hematopoietic and endothelial cells. Proliferating hematopoietic cells contained a significant number of colony-forming cells in culture (CFU-C) and in spleen (CFU-S). Among primary AGM cells at 10.5 dpc, sorted TEK+ AGM cells generated hematopoietic cells and platelet endothelial cell adhesion molecule (PECAM)-1(+) endothelial cells on the OP9 stromal layer, while TEK- cells did not. When a ligand for TEK, angiopoietin-1, was added to the single-cell culture of AGM, endothelial cell growth was detected in the wells where hematopoietic colonies grew. Although the incidence was still low (1/135), we showed that single TEK+ cells generated hematopoietic cells and endothelial cells simultaneously, using a single-cell deposition system. This in vitro coculture system shows that the TEK+ fraction of primary AGM cells is a candidate for hemangioblasts, which can differentiate into both hematopoietic cells and endothelial cells.  (+info)

Organ-selective homing defines engraftment kinetics of murine hematopoietic stem cells and is compromised by Ex vivo expansion. (8/11748)

Hematopoietic reconstitution of ablated recipients requires that intravenously (IV) transplanted stem and progenitor cells "home" to organs that support their proliferation and differentiation. To examine the possible relationship between homing properties and subsequent engraftment potential, murine bone marrow (BM) cells were labeled with fluorescent PKH26 dye and injected into lethally irradiated hosts. PKH26(+) cells homing to marrow or spleen were then isolated by fluorescence-activated cell sorting and assayed for in vitro colony-forming cells (CFCs). Progenitors accumulated rapidly in the spleen, but declined to only 6% of input numbers after 24 hours. Although egress from this organ was accompanied by a simultaneous accumulation of CFCs in the BM (plateauing at 6% to 8% of input after 3 hours), spleen cells remained enriched in donor CFCs compared with marrow during this time. To determine whether this differential homing of clonogenic cells to the marrow and spleen influenced their contribution to short-term or long-term hematopoiesis in vivo, PKH26(+) cells were sorted from each organ 3 hours after transplantation and injected into lethally irradiated Ly-5 congenic mice. Cells that had homed initially to the spleen regenerated circulating leukocytes (20% of normal counts) approximately 2 weeks faster than cells that had homed to the marrow, or PKH26-labeled cells that had not been selected by a prior homing step. Both primary (17 weeks) and secondary (10 weeks) recipients of "spleen-homed" cells also contained approximately 50% higher numbers of CFCs per femur than recipients of "BM-homed" cells. To examine whether progenitor homing was altered upon ex vivo expansion, highly enriched Sca-1(+)c-kit+Lin- cells were cultured for 9 days in serum-free medium containing interleukin (IL)-6, IL-11, granulocyte colony-stimulating factor, stem cell factor, flk-2/flt3 ligand, and thrombopoietin. Expanded cells were then stained with PKH26 and assayed as above. Strikingly, CFCs generated in vitro exhibited a 10-fold reduction in homing capacity compared with fresh progenitors. These studies demonstrate that clonogenic cells with differential homing properties contribute variably to early and late hematopoiesis in vivo. The dramatic decline in the homing capacity of progenitors generated in vitro underscores critical qualitative changes that may compromise their biologic function and potential clinical utility, despite their efficient numerical expansion.  (+info)

With the expression bone marrow hematopoietic stem cell transplant we intend a complex procedure used especially, but not only, in the treatment of leukimias and lymphomas. Stem cells can be obtained not only from bone marrow but also from peripheral blood after a specific preconditioning of the patient, or from umbilical-cord blood.. Indications for hematopoietic stem cell transplant are acute leukimias, chronic leukimias, different forms of bone marrow insufficiency, thalassemias, Hodgkin lymphoma, non Hodgkin lymphomas, myelomas, other chronic myeloproliferative diseases, numerous genetic disorders and, as a recent indication, some autoimmune illnesses.. ...
TY - JOUR. T1 - CD34 expression on long-term repopulating hematopoietic stem cells changes during developmental stages. AU - Matsuoka, Sahoko. AU - Ebihara, Yasuhiro. AU - Xu, Ming Jiang. AU - Ishii, Takefumi. AU - Sugiyama, Daisuke. AU - Yoshino, Hiroshi. AU - Ueda, Takahiro. AU - Manabe, Atsushi. AU - Tanaka, Ryuhei. AU - Ikeda, Yasuo. AU - Nakahata, Tatsutoshi. AU - Tsuji, Kohichiro. PY - 2001/1/15. Y1 - 2001/1/15. N2 - The CD34 antigen serves as an important marker for primitive hematopoietic cells in therapeutic transplantation of hematopoietic stem cells (HSC) and gene therapy, but it has remained an open question as to whether or not most HSC express CD34. Using a competitive long-term reconstitution assay, the results of this study confirm developmental changes in CD34 expression on murine HSC. In fetuses and neonates, CD34 was expressed on Lin-c-Kit+ long-term repopulating HSC of bone marrow (BM), liver, and spleen. However, CD34 expression on HSC decreased with aging, and in mice older ...
HemoGenyx is a preclinical-stage biotechnology company focused on the discovery, development and commercialisation of novel therapies and treatments for blood diseases, like leukemia and lymphoma. The companys leading technologies aim to change the way in which bone marrow/hematopoietic stem cell (BM/HSC) transplants are performed and improve their efficacy.
TY - JOUR. T1 - Runx1 expression marks long-term repopulating hematopoietic stem cells in the midgestation mouse embryo. AU - North, Trista E.. AU - De Bruijn, Marella F T R. AU - Stacy, Terryl. AU - Talebian, Laleh. AU - Lind, Evan. AU - Robin, Catherine. AU - Binder, Michael. AU - Dzierzak, Elaine. AU - Speck, Nancy A.. PY - 2002. Y1 - 2002. N2 - Hematopoietic stem cells (HSCs) are first found in the aorta-gonad-mesonephros region and vitelline and umbilical arteries of the midgestation mouse embryo. Runx1 (AML1), the DNA binding subunit of a core binding factor, is required for the emergence and/or subsequent function of HSCs. We show that all HSCs in the embryo express Runx1. Furthermore, HSCs in Runx1+/- embryos are heterogeneous and include CD45+ cells, endothelial cells, and mesenchymal cells. Comparison with wild-type embryos showed that the distribution of HSCs among these various cell populations is sensitive to Runx1 dosage. These data provide the first morphological description of ...
TY - JOUR. T1 - The repopulation potential of fetal liver hematopoietic stem cells in mice exceeds that of their adult bone marrow counterparts. AU - Rebel, Vivienne I.. AU - Miller, Cindy L.. AU - Eaves, Connie J.. AU - Lansdorp, Peter M.. PY - 1996/4/15. Y1 - 1996/4/15. N2 - Varying, limiting numbers of unseparated or purified cells (Ly-5.1), either from 14.5-day-old fetal liver (FL) or from adult bone marrow (BM) were coinjected with 105 unseparated BM cells (Ly-5.2) into lethally irradiated adult C57B1/6 recipients (Ly-5.2). The kinetics of donor cell repopulation of the lymphoid and myeloid compartments by Ly-5.1+ donor hematopoietic stem cells (ie, competitive repopulation units [CRU]) were monitored at various time points after the transplantation by Ly-5 analysis of the peripheral white blood cells (WBC). Recipients that had received on average less than 2 adult BM or FL CRU did not show a significant difference in the level of donor-reconstitution when analyzed 4 weeks after the ...
Hematopoietic stem cells (HSCs) residing in the bone marrow (BM) accumulate during aging but are functionally impaired. However, the role of HSC-intrinsic and -extrinsic aging mechanisms remains debated. Megakaryocytes promote quiescence of neighboring HSCs. Nonetheless, whether megakaryocyte-HSC interactions change during pathological/natural aging is unclear. Premature aging in Hutchinson-Gilford progeria syndrome recapitulates physiological aging features, but whether these arise from altered stem or niche cells is unknown. Here, we show that the BM microenvironment promotes myelopoiesis in premature/physiological aging. During physiological aging, HSC-supporting niches decrease near bone but expand further from bone. Increased BM noradrenergic innervation promotes β2-adrenergic-receptor(AR)-interleukin-6-dependent megakaryopoiesis. Reduced β3-AR-Nos1 activity correlates with decreased endosteal niches and megakaryocyte apposition to sinusoids. However, chronic treatment of progeroid mice with β3
TY - JOUR. T1 - Self-renewal of a purified Tie2+ hematopoietic stem cell population relies on mitochondrial clearance. AU - Ito, Kyoko. AU - Turcotte, Raphaël. AU - Cui, Jinhua. AU - Zimmerman, Samuel E.. AU - Pinho, Sandra. AU - Mizoguchi, Toshihide. AU - Arai, Fumio. AU - Runnels, Judith M.. AU - Alt, Clemens. AU - Teruya-Feldstein, Julie. AU - Mar, Jessica C.. AU - Singh, Rajat. AU - Suda, Toshio. AU - Lin, Charles P.. AU - Frenette, Paul S.. AU - Ito, Keisuke. PY - 2016/12/2. Y1 - 2016/12/2. N2 - A single hematopoietic stem cell (HSC) is capable of reconstituting hematopoiesis and maintaining homeostasis by balancing self-renewal and cell differentiation. The mechanisms of HSC division balance, however, are not yet defined. Here we demonstrate, by characterizing at the single-cell level a purified and minimally heterogeneous murine Tie2+ HSC population, that these top hierarchical HSCs preferentially undergo symmetric divisions. The induction of mitophagy, a quality control process in ...
TY - JOUR. T1 - Functional association between expression of adhesion molecules and marrow repopulating potential of primitive murine hematopoietic progenitor cells (hpc). AU - Travcpff, C. M.. AU - Voder, M. C.. AU - Hiatt, K.. AU - Srour, Edward. PY - 1997. Y1 - 1997. N2 - A number of adhesion molecules have been implicated in the ability of transplanted hematopoietic stem cells (HSC) to engraft. We investigated whether the expression, or lack thereof, of CD11 a, CD43, CD44, CD49d, CD49e, and CD62L on Sca-1 + lin- cells augments or diminishes the bone marrow (BM) repoputatlng potential of these cells. A total of 103 Sca-l+ lin X+ or Sca-1+ lin X- cells (where X is any of the 6 molecules mentioned above) from B6.Hbbd congenic mice were competitively transplanted along with 3 x 104 C57/BI6 low density BM cells into fethally irradiated C57/BI6 recipients. In the event where all analyzed Sca-1+ Ifrr cells were positive for the expression of a particular adhesion molecule (CD44 and CD49d), Sca-1 ...
TY - JOUR. T1 - Prostaglandin E2 enhances hematopoietic stem cell homing, survival, and proliferation. AU - Hoggatt, Jonathan. AU - Singh, Pratibha. AU - Sampath, Janardhan. AU - Pelus, Louis M.. PY - 2009. Y1 - 2009. N2 - Adult hematopoietic stem cells (HSCs) are routinely used to reconstitute hematopoiesis after myeloablation; however, transplantation efficacy and multilineage reconstitution can be limited by inadequate HSC number, or poor homing, engraftment, or self-renewal. Here we report that mouse and human HSCs express prostaglandin E2 (PGE2) receptors, and that short-term ex vivo exposure of HSCs to PGE2 enhances their homing, survival, and proliferation, resulting in increased long-term repopulating cell (LTRC) and competitive repopulating unit (CRU) frequency. HSCs pulsed with PGE2 are more competitive, as determined by head-to-head comparison in a competitive transplantation model. Enhanced HSC frequency and competitive advantage is stable and maintained upon serial transplantation, ...
Hematopoietic stem cells (HSCs) are first found in the aorta-gonad-mesonephros region and vitelline and umbilical arteries of the midgestation mouse embryo. Runx1 (AML1), the DNA binding subunit of a core binding factor, is required for the emergence and/or subsequent function of HSCs. We show that all HSCs in the embryo express Runx1. Furthermore, HSCs in Runx1(+/-) embryos are heterogeneous and include CD45(+) cells, endothelial cells, and mesenchymal cells. Comparison with wild-type embryos showed that the distribution of HSCs among these various cell populations is sensitive to Runx1 dosage. These data provide the first morphological description of embryonic HSCs and contribute new insight into their cellular origin.
Hematopoietic Stem Cell Biology is the newest installment in the Stem Cell Biology and Regenerative Medicine series, to which it adeptly contributes as it offers a selection of carefully chosen topics so that the readers can understand recent advances in the field of the hematopoietic stem cells and hemato/lymphopoiesis. Each chapter is not a simple review of the topic, but rather an in-depth insight, which allows the reader to attain a multifaceted knowledgebase on hematopoietic stem cells. The chapters, which are authored by the leading experts in the field, cover characteristics of the hematopoietic stem cells at the cellular and molecular levels, offers details in regulatory mechanisms of differentiation mechanisms of hematopoietic stem cells to more mature blood cell, and discusses abnormal hematopoiesis that leads to leukemia. Hematopoietic Stem Cell Biology serves the inquiring minds of researchers, graduate students and post doctorate fellows as it expertly addresses the ever-growing ...
Hematopoietic Stem Cell Biology is the newest installment in the Stem Cell Biology and Regenerative Medicine series, to which it adeptly contributes as it offers a selection of carefully chosen topics so that the readers can understand recent advances in the field of the hematopoietic stem cells and hemato/lymphopoiesis. Each chapter is not a simple review of the topic, but rather an in-depth insight, which allows the reader to attain a multifaceted knowledgebase on hematopoietic stem cells. The chapters, which are authored by the leading experts in the field, cover characteristics of the hematopoietic stem cells at the cellular and molecular levels, offers details in regulatory mechanisms of differentiation mechanisms of hematopoietic stem cells to more mature blood cell, and discusses abnormal hematopoiesis that leads to leukemia. Hematopoietic Stem Cell Biology serves the inquiring minds of researchers, graduate students and post doctorate fellows as it expertly addresses the ever-growing ...
Quiescent long-term hematopoietic stem cells (LT-HSCs) are efficiently activated by type I interferon (IFN-I). However, this effect remains poorly investigated in the context of IFN-I-inducing virus infections. Here we report that both vesicular stomatitis virus (VSV) and murine cytomegalovirus (MCMV) infection induce LT-HSC activation that substantially differs from the effects triggered upon injection of synthetic IFN-I-inducing agents. In both infections, inflammatory responses had to exceed local thresholds within the bone marrow to confer LT-HSC cell cycle entry, and IFN-I receptor triggering was not critical for this activation. After resolution of acute MCMV infection, LT-HSCs returned to phenotypic quiescence. However, non-acute MCMV infection induced a sustained inflammatory milieu within the bone marrow that was associated with long-lasting impairment of LT-HSC function. In conclusion, our results show that systemic virus infections fundamentally affect LT-HSCs and that also non-acute ...
Background Many biological processes are characterized by allometric relations of the type Y = Y0Mb between an observable Y and body mass M, which pervade at multiple levels of organization. In what regards the hematopoietic stem cell pool, there is experimental evidence that the size of the hematopoietic stem cell pool is conserved in mammals. However, demands for blood cell formation vary across mammals and thus the size of the active stem cell compartment could vary across species. Methodology/Principle Findings Here we investigate the allometric scaling of the hematopoietic system in a large group of mammalian species using reticulocyte counts as a marker of the active stem cell pool. Our model predicts that the total number of active stem cells, in an adult mammal, scales with body mass with the exponent ¾. Conclusion/Significance The scaling predicted here provides an intuitive justification of the Hayflick hypothesis and supports the current view of a small active stem cell pool supported by a
TY - JOUR. T1 - Suppression and potentiation of mouse hematopoietic progenitor cell proliferation by ouabain. AU - Spivak, J. L.. AU - Misiti, J.. AU - Stuart, R.. AU - Sharkis, S. J.. AU - Sensenbrenner, L. L.. PY - 1980. Y1 - 1980. N2 - Clonal assays for CFU-S, CFU-C, BFU-E, and CFU-E were employed to evaluate the effect of ouabain on the proliferation of mouse hematopoietic progenitor cells. Preincubation of bone marrow cells with ouabain at concentrations of 10-6-10-12 M suppressed the proliferation of CFU-S as measured by the spleen colony assay. At 10-9 M ouabain, spleen colony formation was inhibited by more than 95%. When included in soft agar cultures of bone marrow cells, ouabain suppressed the proliferation of CFU-C in a complex fashion. At 10-4 M ouabain, colony formation was suppressed by 70%, while at 10-6 M ouabain, CFU-C proliferation was normal. At 10-9 M ouabain, however, the number of colonies formed was only 70% of normal, and complete recovery was not obtained at 10-12 M ...
The current paradigm that a single long-term hematopoietic stem cell can regenerate all components of the mammalian immune system has been challenged by recent findings in mice. These findings show that adult tissue-resident macrophages and innate-like lymphocytes develop early in fetal hematopoiesis from progenitors that emerge prior to, and apparently independently of, conventional long-term hematopoietic stem cells. Here, we discuss these recent findings, which show that an early and distinct wave of hematopoiesis occurs for all major hematopoietic lineages. These data provide evidence that fetal hematopoietic progenitors not derived from the bona fide long-term hematopoietic stem cells give rise to tissue-resident immune cells that persist throughout adulthood. We also discuss recent insights into B lymphocyte development and attempt to synthesize seemingly contradictory recent findings on the origins of innate-like B-1a lymphocytes during fetal hematopoiesis ...
TY - JOUR. T1 - Endothelial cells provide a niche for placental hematopoietic stem/progenitor cell expansion through broad transcriptomic modification. AU - Raynaud, Christophe M.. AU - Butler, Jason M.. AU - Halabi, Najeeb M.. AU - Ahmad, Faizzan S.. AU - Ahmed, Badereldeen. AU - Rafii, Shahin. AU - Rafii, Arash. PY - 2013/11/1. Y1 - 2013/11/1. N2 - Umbilical cord blood (UCB) is an attractive source of hematopoietic stem cells (HSCs). However, the number of HSCs in UCB is limited, and attempts to amplify them in vitro remain inefficient. Several publications have documented amplification of hematopoietic stem/progenitor cells (HSPCs) on endothelial or mesenchymal cells, but the lack of homogeneity in culture conditions and HSC definition impairs direct comparison of these results. We investigated the ability of different feeder layers, mesenchymal progenitors (MPs) and endothelial cells (ECs), to amplify hematopoietic stem/progenitor cells. Placental derived HSPCs (defined as ...
TY - JOUR. T1 - The Paf oncogene is essential for hematopoietic stem cell function and development. AU - Amrani, Yacine M.. AU - Gill, Jonathan. AU - Matevossian, Armine. AU - Alonzo, Eric S.. AU - Yang, Chingwen. AU - Shieh, Jae Hung. AU - Moore, Malcolm A.. AU - Park, Christopher Y.. AU - SantAngelo, Derek B.. AU - Denzin, Lisa K.. PY - 2011/8/29. Y1 - 2011/8/29. N2 - Hematopoietic stem cells (HSCs) self-renew to maintain the lifelong production of all blood populations. Here, we show that the proliferating cell nuclear antigen-associated factor (Paf) is highly expressed in cycling bone marrow HSCs and plays a critical role in hematopoiesis. Mice lacking Paf exhibited reduced bone marrow cellularity; reduced numbers of HSCs and committed progenitors; and leukopenia. These phenotypes are caused by a cellintrinsic blockage in the development of long-term (LT)-HSCs into multipotent progenitors and preferential loss of lymphoid progenitors caused by markedly increased p53-mediated apoptosis. In ...
TY - JOUR. T1 - Primitive adult hematopoietic stem cells can function as osteoblast precursors. AU - Olmsted-Davis, Elizabeth A.. AU - Gugala, Zbigniew. AU - Camargo, Fernando. AU - Gannon, Francis H.. AU - Jackson, KathyJo. AU - Kienstra, Kirsten Anderson. AU - Shine, H. David. AU - Lindsey, Ronald. AU - Hirschi, Karen K.. AU - Goodell, Margaret A.. AU - Brenner, Malcolm K.. AU - Davis, Alan R.. PY - 2003/12/23. Y1 - 2003/12/23. N2 - Osteoblasts are continually recruited from stem cell pools to maintain bone. Although their immediate precursor is a plastic-adherent mesenchymal stem cell able to generate tissues other than bone, increasing evidence suggests the existence of a more primitive cell that can differentiate to both hematopoietic and mesenchymal cells. We show here that the side population (SP) of marrow stem cells, defined by their ability to rapidly expel a DNA-binding dye and to regenerate the hematopoietic compartment, can differentiate to osteoblasts through a mesenchymal ...
Whereas the cellular basis of the hematopoietic stem cell (HSC) niche in the bone marrow has been characterized, the nature of the fetal liver niche is not yet elucidated. We show that Nestin+NG2+ pericytes associate with portal vessels, forming a niche promoting HSC expansion. Nestin+NG2+ cells and HSCs scale during development with the fractal branching patterns of portal vessels, tributaries of the umbilical vein. After closure of the umbilical inlet at birth, portal vessels undergo a transition from Neuropilin-1+Ephrin-B2+ artery to EphB4+ vein phenotype, associated with a loss of periportal Nestin+NG2+ cells and emigration of HSCs away from portal vessels. These data support a model in which HSCs are titrated against a periportal vascular niche with a fractal-like organization enabled by placental circulation. ...
Although previous studies suggested that the expression of FMS-like tyrosine kinase 3 (Flt3) initiates downstream of mouse hematopoietic stem cells (HSCs),FLT3internal tandem duplications (FLT3ITDs) have recently been suggested to intrinsically suppress HSCs. Herein, single-cell interrogation foundFlt3mRNA expression to be absent in the large majority of phenotypic HSCs, with a strong negative correlation betweenFlt3and HSC-associated gene expression. Flt3-ITD knock-in mice showed reduced numbers of phenotypic HSCs, with an even more severe loss of long-term repopulating HSCs, likely reflecting the presence of non-HSCs within the phenotypic HSC compartment. Competitive transplantation experiments established that Flt3-ITD compromises HSCs through an extrinsically mediated mechanism of disrupting HSC-supporting bone marrow stromal cells, with reduced numbers of endothelial and mesenchymal stromal cells showing increased inflammation-associated gene expression. Tumor necrosis factor (TNF), a cell
TY - JOUR. T1 - Evidence that hematopoietic stem cells in human umbilical cord blood is infectable by dengue virus. T2 - proposing a vertical transmission candidate. AU - Vats, Amrita. AU - Ho, Tzu Chuan. AU - Puc, Irwin. AU - Chen, Yi Ju. AU - Chang, Chiung Hsin. AU - Chien, Yu Wen. AU - Perng, Guey Chuen. N1 - Funding Information: This work was supported by Taiwan Ministry of Science and Technology ( MOST-106-2321-B-006-012 ; MOST 107-2314-B-006-MY3 and MOST 103-2320-B-006-030-MY3 ). Publisher Copyright: © 2021 The Author(s). PY - 2021/4. Y1 - 2021/4. N2 - Background: Recent studies have shown that dengue virus (DENV) can efficiently infect bone marrow hematopoietic stem cells (HSCs) as well as the placenta of pregnant women. Although mother-to-infant vertical transmission of DENV through the placenta has been well documented, the evidence of cell-associated vertical transmission is still unknown. Whether DENV can infect umbilical cord blood (UCB) cells before reaching the fetus remains to be ...
TY - JOUR. T1 - In vivo T-cell dynamics during immune reconstitution after hematopoietic stem cell gene therapy in adenosine deaminase severe combined immune deficiency. AU - Selleri, Silvia. AU - Brigida, Immacolata. AU - Casiraghi, Miriam. AU - Scaramuzza, Samantha. AU - Cappelli, Barbara. AU - Cassani, Barbara. AU - Ferrua, Francesca. AU - Aker, Memet. AU - Slavin, Shimon. AU - Scarselli, Alessia. AU - Cancrini, Caterina. AU - Marktel, Sarah. AU - Grazia Roncarolo, Maria. AU - Aiuti, Alessandro. PY - 2011/6. Y1 - 2011/6. N2 - Background: Gene therapy (GT) with hematopoietic stem cells is a promising treatment for inherited immunodeficiencies. Objectives: Limited information is available on the relative contribution of de novo thymopoiesis and peripheral expansion to T-cell reconstitution after GT as well as on the potential effects of gene transfer on hematopoietic stem cells and lymphocyte replicative lifespan. We studied these issues in patients affected by adenosine deaminase severe ...
The CD105 MultiSort Kit (PE), mouse has been developed for the isolation of CD105+ cells or cell subsets, including vascular endothelial cells from mouse tissue or cell cultures long-term repopulating hematopoietic stem cells (LTR-HSCs) from mouse bone marrow when used in combination with the Anti-Sca-1 MicroBead Kit (FITC). - USA
TY - JOUR. T1 - Osteoclasts are dispensable for hematopoietic stem cell maintenance and mobilization. AU - Miyamoto, Kana. AU - Yoshida, Shigeyuki. AU - Kawasumi, Miyuri. AU - Hashimoto, Kazuaki. AU - Kimura, Tokuhiro. AU - Sato, Yuiko. AU - Kobayashi, Tami. AU - Miyauchi, Yoshiteru. AU - Hoshi, Hiroko. AU - Iwasaki, Ryotaro. AU - Miyamoto, Hiroya. AU - Hao, Wu. AU - Morioka, Hideo. AU - Chiba, Kazuhiro. AU - Kobayashi, Takashi. AU - Yasuda, Hisataka. AU - Penninger, Josef M.. AU - Toyama, Yoshiaki. AU - Suda, Toshio. AU - Miyamoto, Takeshi. PY - 2011/12/19. Y1 - 2011/12/19. UR - UR - U2 - 10.1084/jem.2010189020813c. DO - 10.1084/jem.2010189020813c. M3 - Article. AN - SCOPUS:84862936378. VL - 208. SP - 2761. JO - Journal of Experimental Medicine. JF - Journal of Experimental Medicine. SN - 0022-1007. IS - 13. ER - ...
There are comments on PubPeer for publication: Ezh1 is required for hematopoietic stem cell maintenance and prevents senescence-like cell cycle arrest (2012)
The only curative therapy for sickle cell disease (SCD) is allogeneic hematopoietic stem cell (HSC) transplantation. Gene therapy approaches for autologous HSC transplantation are being developed. Although earlier engraftment is seen when cells from GCSF-mobilized blood are transplanted than when bone marrow is transplanted, administration of GCSF to patients with SCD can cause significant morbidity. We tested whether primitive hematopoietic progenitors are spontaneously mobilized in the blood of patients with SCD during acute crisis (AC-SCD patients). The frequency of myeloid-lymphoid-initiating cells (ML-ICs) and SCID-repopulating cells (SRCs) was significantly higher in blood from AC-SCD patients than in blood from patients with steady-state SCD or from normal donors. The presence of SRCs in peripheral blood was not associated with detection of long-term culture-initiating cells, consistent with the notion that SRCs are more primitive than long-term culture-initiating cells. As ML-ICs and ...
Hematopoietic stem cells (HSCs) give rise to all blood populations due to their long-term self-renewal and multipotent differentiation capacities. Because they have to persist throughout an organisms life span, HSCs tightly regulate the balance between proliferation and quiescence. Here, we investigated the role of the transcription factor promyelocytic leukemia zinc finger (plzf) in HSC fate using the Zbtb16(lu/lu)mouse model, which harbors a natural spontaneous mutation that inactivates plzf. Regenerative stress revealed that Zbtb16(lu/lu)HSCs had a lineage-skewing potential from lymphopoiesis toward myelopoiesis, an increase in the long-term-HSC pool, and a decreased repopulation potential. Furthermore, oldplzf-mutant HSCs present an amplified aging phenotype, suggesting that plzf controls age-related pathway. We found that Zbtb16(lu/lu)HSCs harbor a transcriptional signature associated with a loss of stemness and cell cycle deregulation. Lastly, cell cycle analyses revealed an important ...
TY - JOUR. T1 - Critical role of Jak2 in the maintenance and function of adult hematopoietic stem cells. AU - Akada, Hajime. AU - Akada, Saeko. AU - Hutchison, Robert E.. AU - Sakamoto, Kazuhito. AU - Wagner, Kay Uwe. AU - Mohi, Golam. PY - 2014/7. Y1 - 2014/7. N2 - Jak2, a member of the Janus kinase family of nonreceptor protein tyrosine kinases, is activated in response to a variety of cytokines, and functions in survival and proliferation of cells. An activating JAK2V617F mutation has been found in most patients with myeloproliferative neoplasms, and patients treated with Jak2 inhibitors show significant hematopoietic toxicities. However, the role of Jak2 in adult hematopoietic stem cells (HSCs) has not been clearly elucidated. Using a conditional Jak2 knockout allele, we have found that Jak2 deletion results in rapid loss of HSCs/progenitors leading to bone marrow failure and early lethality in adult mice. Jak2 deficiency causes marked impairment in HSC function, and the mutant HSCs are ...
Maintenance of blood homeostasis depends on the balance between self-renewal of hematopoietic stem cells (HSCs) and their differentiation into blood cell progenitors. A variety of different intrinsic or extrinsic regulators, including multiple microRNA (miRNA) species, have been described to play a role in the regulation of these processes. Disruption of any of these regulators could lead to stem cell exhaustion or increased risk of leukemogenesis. Given recent reports of the role of miR-146a in malignant hematopoiesis, we evaluated its role in hematopoietic stem progenitor cell (HSPC) function. We show that miR-146a is highly expressed in HSCs and its expression decreases in committed progenitors. miR-146a- deficient HSCs had dramatically reduced self-renewal capacity as measured by serial competitive bone marrow transplantation assays. The lower self-renewal capacity was accompanied by decreased quiescence in miR-146a-deficient cells, as revealed by decreased proportion of miR-146a-/- HSPCs ...
Holmes, T., Yan, F., Ko, K.-H., Nordon, R., Song, E., OBrien, T. A. and Dolnikov, A. (2012), Ex vivo expansion of cord blood progenitors impairs their short-term and long-term repopulating activity associated with transcriptional dysregulation of signalling networks. Cell Proliferation, 45: 266-278. doi: 10.1111/j.1365-2184.2012.00813.x ...
Adult hematopoietic stem cells (HSCs) are maintained in a microenvironment, known as niche in the endosteal regions of the bone marrow. This stem cell niche with low oxygen tension requires HSCs to adopt a unique metabolic profile. We have recently demonstrated that mouse long-term hematopoietic stem cells (LT-HSCs) utilize glycolysis instead of mitochondrial oxidative phosphorylation as their main energy source. However, the metabolic phenotype of human hematopoietic progenitor and stem cells (HPSCs) remains unknown. We show that HPSCs have a similar metabolic phenotype, as shown by high rates of glycolysis, and low rates of oxygen consumption. Fractionation of human mobilized peripheral blood cells based on their metabolic footprint shows that cells with a low mitochondrial potential are highly enriched for HPSCs. Remarkably, low MP cells had much better repopulation ability as compared to high MP cells. Moreover, similar to their murine counterparts, we show that Hif-1α is upregulated in human HPSCs
PRIME-XV® Mouse Hematopoietic Cell Basal Medium was developed in a collaboration program with a leading stem-cell research facility in the USA to fulfill the need for a serum-free, cost-effective medium for in vitro culture and expansion and self-renewal of murine hematopoietic progenitor cells (mHPCs).. PRIME-XV Mouse Hematopoietic Cell Basal Medium is:. ...
During embryonic development a variety of tissues and organs such as the lung, eye, and kidney are being formed. The generation of functional organs is regulated by reciprocal cell-cell interactions. Via the secretion of soluble molecules one type of cells affect the fate of their neighboring cells. A central issue in organogenesis is how a cell interprets such extrinsic signals and adopts a specific fate, and how the cell in response to this signal establishes reciprocal signaling. Transcription factors play a critical role in this process and my thesis focuses on the role of the LIM-homeodomain transcription factor, Lhx2, in the development of three different organ systems, the liver, the hematopoietic system and the olfactory system.. The liver is formed from endoderm of the ventral foregut and mesenchyme of the septum transversum (st) and its development depends upon signaling interactions between these two tissues. As the liver becomes a distinct organ it is colonized by hematopoietic cells ...
Wnt signaling increases hematopoietic stem cell self-renewal and is activated in both myeloid and lymphoid malignancies, indicating involvement in both normal and malignant hematopoiesis. We report here activated canonical Wnt signaling in the hematopoietic system through conditional expression of a stable form of beta-catenin. This enforced expression led to hematopoietic failure associated with loss of myeloid lineage commitment at the granulocyte-macrophage progenitor stage; blocked erythrocyte differentiation; disruption of lymphoid development; and loss of repopulating stem cell activity. Loss of hematopoietic stem cell function was associated with decreased expression of Cdkn1a ( encoding the cell cycle inhibitor p21(cdk)), Sfpi1, Hoxb4 and Bmi1 ( encoding the transcription factors PU.1, HoxB4 and Bmi-1, respectively) and altered integrin expression in Lin(-)Sca-1(+)c-Kit(+) cells, whereas PU.1 was upregulated in erythroid progenitors. Constitutive activation of canonical Wnt signaling ...
Hematopoiesis is a complex process through which hematopoietic stem cells (HSCs) generate all the cell types found in the blood. This originates during the early stages of embryonic development and continues in the bone marrow (BM) throughout adulthood to preserve homeostasis in the blood system. The interest in the expansion and production of HSCs has increased in recent years. After the derivation of human embryonic stem cells (ESCs) and the discovery of cellular reprogramming, much effort has been devoted to obtain HSCs and mature blood cells from human pluripotent stem cells (PSCs). In addition to their unlimited, yet-to-be realized, therapeutic potential, human PSCs make a very useful tool that can be utilized to understand the signaling pathways involved in hematopoiesis. Recently, long term engraftment and multi-lineage differentiation of hPSCs-derived hematopoietic progenitor cells was achieved after screening large numbers of potential transcription factors that were activated in vivo ...
Bennett, M and Cudkowicz, G, Hemopoietic precursor cells of the mouse spleen incapable of self- -replication. Abstr. (1967). Subject Strain Bibliography 1967. 1376 ...
TY - JOUR. T1 - Rapid 1-hour transduction of whole bone marrow leads to long-term repopulation of murine recipients with lentivirus-modified hematopoietic stem cells. AU - Kurre, Peter. AU - Anandakumar, P.. AU - Kiem, H. P.. PY - 2006/2. Y1 - 2006/2. N2 - Efficient gene transfer to hematopoietic stem cells by Moloney murine leukemia virus-derived retroviral vectors benefits from ex vivo culture and cytokine support. Both also increase the risks of apoptosis and differentiation among cells targeted for transduction. In an effort to maximize the retention of stem cell properties in target cells, we developed a transduction protocol with a focus on minimizing graft manipulation, cytokine stimulation, and ex vivo exposure duration. Based on their wide host range and ability to transduce quiescent cells, human immunodeficiency virus (HIV)-derived lentivirus vectors are ideally suited for this purpose. Our present studies in a murine model show that whole bone marrow cells are readily transduced ...
Gpr56, one of the top hits in our HSC versus HEC comparison (30-fold increase) and bound by all heptad TFs, is indeed a novel regulator for emerging HSCs in the embryonic vasculature. Contrary to expectations raised by the lack of HSC defects in mouse Gpr56 KO embryos (generated by deletion of the first two exons [Saito et al. 2013]), our RNAseq data suggested a strong role for Gpr56 in emergence of HSCs. In the E10.5 mouse aorta, we localized Gpr56 expression to a few HCs/HSCs (Ly6aGFP+). Upon gpr56 knockdown, zebrafish embryos showed severe reduction in HSCs (cmyb) and CD41+ hematopoietic stem/progenitor cells, revealing a requirement for Gpr56 in HSC generation. Our rescue experiments in gpr56 morphants show that both zebrafish and mouse Gpr56 RNA can restore aortic hematopoietic stem/progenitor generation. Moreover, Gpr56 overexpression resulted in ectopic hematopoietic progenitor/stem cell formation in the axial vein, suggesting that the Gpr56 signaling axis may be useful for inducing new ...
Abstract. We show here for the first time that pluripotent hematopoietic stem cells express the CD4 antigen. CD4+ cells isolated from mouse marrow repopulated
Receptor tyrosine kinase (RTK) c-Kit signalling is crucial for the proliferation, survival and differentiation of haematopoietic stem cells (HSCs). To further understand the mechanisms underlying these events we explored how the downstream mediators interact. The present study investigated the function of conventional protein kinase Cs (c-PKC) in c-Kit mediated signalling pathways in HSC-like cell lines. This analysis supported earlier findings, that steel factor (SF) activates c-PKC, extracellular signal-regulated kinase (Erk) and protein kinase B (PKB). The present results were consistent with an important role of c-PKC in the positive activation of Erk and for proliferation. Further, it was observed that c-PKC negatively regulated PKB activity upon SF stimulation, indicating that c-PKC acts as a suppressor of c-Kit signalling. Finally, these observations were extended to show that c-PKC mediated the phosphorylation of the endogenous c-Kit receptor on serine 746, resulting in decreased overall ...
TY - JOUR. T1 - Recognition of a Caucasoid HLA-B locus allele, B*44. T2 - 55, in a Taiwanese/Chinese bone marrow stem cell donor. AU - Yang, K. L.. AU - Lee, S. K.. AU - Kao, R. H.. AU - Lin, C. L.. AU - Lin, P. Y.. PY - 2013/4/1. Y1 - 2013/4/1. N2 - Summary: We detected a Caucasoid HLA-B allele, HLA-B*44:55, in a potential Taiwanese/Chinese bone marrow hematopoietic stem cell donor during our routine HLA SBT (sequence-based typing) practice. The sequence of B*44:55 varies with B*44:02:01:01 with one nucleotide in exon 2 at position 97 (T-,C), while it differs from B*44:03:01 with one nucleotide in exon 2 at position 97 (T-,C) and three nucleotides in exon 3 at residues 538-540 (CTG-,GAC). The nucleotide replacements caused one amino acid variation with B*44:02:01:01 at residue 9 (Y-,H) and two amino acid variations with B*44:03:01 at residue 9 (Y-,H) and residue 156 (L-,D). The formation of B*44:55 is probably the result of a nucleotide substitution involving B*44:02:01:01 at position 97 ...
Two categories of blood-forming stem cells exist in adult bone marrow. One population can provide permanent long-term reconstitution of the entire hematopoietic system. These cells, referred to as hematopoietic stem cells (HSCs), are rare, perhaps as few as 1:10 000 bone marrow cells.28 However, utilizing the specificity of monoclonal antibodies, HSCs can be enriched by flow cytometry to near purity on the basis of surface markers. As few as 20 to 100 highly purified mouse bone marrow HSCs can reconstitute the entire lymphohematopoietic system in myeloablated adult mice.29-31 They can self-renew and can differentiate into the more mature progenitor cells in bone marrow.. The progenitor cells of bone marrow have a limited capacity for self-renewal and differentiation. They can only sustain hematopoiesis for 1 to 2 months and therefore are considered to be short-term repopulating stem cells. It is proposed that one subclass of mouse progenitor cells, the common lymphocytic progenitors (CLP), ...
The current study identifies a potential interaction between the FA pathway and Notch signaling in HSC differentiation and establishes a role of FA proteins in the control of balance between renewal and lineage commitment. There are several findings that highlight the significance of our study: 1) loss of murine FA proteins results in enhanced Notch signaling in MPPs, which is correlated with decreased phenotypic and functional LT-HSCs and increased formation of MPP1 progenitors; 2) deletion of the Fanca or Fancc gene deregulates genes in the Notch signaling and the NF-κB pathway; 3) TNF-α stimulation enhances Notch signaling in Fanca−/− and Fancc−/− LSK cells, leading to decreased HSC quiescence and compromised HSC self-renewal; 4) inflammation-activated Notch target gene expression in Fanca−/− and Fancc−/− MPP cells requires NF-κB; 5) genetic ablation or pharmacologic inhibition of NF-κB reduces Notch signaling in FA MPPs to near WT levels and significantly increases ...
TY - JOUR. T1 - Haematopoietic stem cells and early lymphoid progenitors occupy distinct bone marrow niches. AU - Ding, Lei. AU - Morrison, Sean J.. PY - 2013/3/14. Y1 - 2013/3/14. N2 - Although haematopoietic stem cells (HSCs) are commonly assumed to reside within a specialized microenvironment, or niche, most published experimental manipulations of the HSC niche have affected the function of diverse restricted progenitors. This raises the fundamental question of whether HSCs and restricted progenitors reside within distinct, specialized niches or whether they share a common niche. Here we assess the physiological sources of the chemokine CXCL12 for HSC and restricted progenitor maintenance. Cxcl12DsRed knock-in mice (DsRed-Express2 recombined into the Cxcl12 locus) showed that Cxcl12 was primarily expressed by perivascular stromal cells and, at lower levels, by endothelial cells, osteoblasts and some haematopoietic cells. Conditional deletion of Cxcl12 from haematopoietic cells or ...
To clarify the molecular pathways governing hematopoietic stem cell (HSC) development, we screened a fetal liver (FL) HSC cDNA library and identified a unique gene, hematopoietic expressed mammalian polycomb (hemp), encoding a protein with a zinc-finger domain and four malignant brain tumor (mbt) repeats. To investigate its biological role, we generated mice lacking Hemp (hemp−/−). Hemp−/− mice exhibited a variety of skeletal malformations and died soon after birth. In the FL, hemp was preferentially expressed in the HSC and early progenitor cell fractions, and analyses of fetal hematopoiesis revealed that the number of FL mononuclear cells, including HSCs, was reduced markedly in hemp−/− embryos, especially during early development. In addition, colony-forming and competitive repopulation assays demonstrated that the proliferative and reconstitution abilities of hemp−/− FL HSCs were significantly impaired. Microarray analysis revealed alterations in the expression levels of ...
Background Cdx4 is a homeobox gene essential for normal blood formation during embryonic development in the zebrafish, through activation of posterior hox genes. However, its role in adult mammalian hematopoiesis has not been extensively studied and its requirement in leukemia associated with Hox gene expression alteration is unclear. Design and Methods We inactivated Cdx4 in mice through either a germline or conditional knockout approach and analyzed requirement for Cdx4 in both normal adult hematopoiesis and leukemogenesis initiated by the MLL-AF9 fusion oncogene. Results Here, we report that loss of Cdx4 had minimal effect on adult hematopoiesis. Indeed, although an increase in white blood cell counts was observed, no significant difference in the distribution of mature blood cells, progenitors or stem cells were observed in Cdx4-deficient animals. In addition, long-term repopulating activity in competitive transplantation assays was not significantly altered. In vitro, B-cell progenitor ...
Since monocytes and macrophages that arise during the culture of bone marrow progenitor cells are potential sources of interleukin 6 (IL-6), we investigated whether auto- or paracrine production of this factor is involved in colony formation by normal hematopoietic progenitor cells. We added a polyclonal anti-IL-6 antiserum and a monoclonal anti-IL-6 antibody to cultures of monocyte- and T cell-depleted bone marrow cells. Colony formation was stimulated with granulocyte/monocyte-colony-stimulating factor (GM-CSF), monocyte-CSF, or IL-3. Addition of anti-IL-6 antibody resulted in decreased numbers of monocytic colonies to 40-50% of control values, whereas the numbers of granulocytic colonies were not altered. The inhibitory effect was preserved in cultures of CD34(+)-enriched bone marrow cells. As a second approach, we added a monoclonal antibody directed against the IL-6 receptor to cultures of monocyte- and T cell-depleted bone marrow cells. This antibody almost completely inhibited the growth ...
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Hematopoietic stem/progenitor cells (HSPCs) maintain the hematopoietic system by balancing their self-renewal and differentiation events. Hematopoietic stem cells also migrate to various sites and interact with their specific microenvironment to maintain the integrity of the system. Rho GTPases have been found to control the migration of hematopoietic cells and other cell types. Although the role of RAC1, RAC2 and CDC42 has been studied, the role of RHOA in human hematopoietic stem cells is unclear. By utilizing constitutively active and dominant negative RHOA, we show that RHOA negatively regulates both in vitro and in vivo migration and dominant negative RHOA significantly increased the migration potential of human HSC/HPCs. Active RHOA expression favors the retention of hematopoietic stem/progenitor cells in the niche rather than migration and was found to lock the cells in the G0 cell cycle phase thereby affecting their long-term self-renewal potential. The current study demonstrates that down
Robust and large-scale expansion of umbilical cord blood stem cells in vitro is necessary for widening the usage of transplantation therapies for the treatment of hematological and immune diseases. The lack of understanding of the complex inter-cellular networks regulating stem cell fate in culture explains the low success met so far for the ex vivo expansion of hematopoietic stem cells. The development of a mathematical model of in vitro hematopoiesis coupled with gene expression profiling led to predictions about the secreted factors that play a crucial role in regulating hematopoietic stem cell self-renewal in culture. We tested 18 putative molecules predicted to display effects on primitive progenitor (Long-Term Culture-Initiating Cell; LTC-IC) output, functionally validating three stimulators (VEGF, PDGF, EGF) and three inhibitors (TGFβ, CCL4, CXCL10). Combinatorial studies with the stimulatory molecules showed less-than additive effects, perhaps related to redundant signaling mechanisms. Small
Zhen F, Lan Y, Yan B, Zhang W, Wen Z. Hemogenic endothelium specification and hematopoietic stem cell maintenance employ distinct Scl isoforms. Development. 20
The invasive fungal infection (IFI) is the most common cause of mortality related to autologous stem cell transplant. Taking into account that Saprophytic Aspergillus is usually acquired by inhalation, to protect the bronchial tree just before the tissue invasion is quite attractive. In haematologic patients, as well as those ones subjected to an Allogeneic haematopoietic progenitor cell transplant, there is another group of patients at high risk of Invasive Pulmonary Aspergillosis (IPA). These are those patients with acute myeloid leucemia (AML), submitted to induction, intensification or consolidation polychemotherapy. The IPA incidence rate in these patients, whenever during their evolution, reaches 18-20%, with usual treatments. Furthermore, unlike allogeneic haematopoietic progenitor cell transplant patients, neutropenia was the only IPA risk factor. Nowadays, pharmacologic prophylaxis against IPA, in patients with allogeneic haematopoietic progenitor cell transplant and patients affected ...
Looking for online definition of Pluripotential hematopoietic stem cell in the Medical Dictionary? Pluripotential hematopoietic stem cell explanation free. What is Pluripotential hematopoietic stem cell? Meaning of Pluripotential hematopoietic stem cell medical term. What does Pluripotential hematopoietic stem cell mean?
According to a recently published report by Brisk Insights, the Global Hematopoietic Stem Cells Transplantation Market is expected to grow at the CAGR of 10.4 % during 2017-2025. The global hematopoietic stem cells transplantation market is segmented on the basis of application, transplant type, and geography. The report on global hematopoietic stem cells transplantation market (by application, transplant type, and geography) provides a detailed overview and predictive analysis of the market.. Full report available on Hematopoietic Stem Cells Transplantation Market: Global Industry Size, Growth, Share and Forecast to 2025 report at Market Insights. Increasing prevalence of cancer and anemia in both developed and developing nations are the key growth factors in the hematopoietic stem cells transplantation market. In base year 2016, lymphoproliferative disorders and leukemia accounted for more than 50% of the ...
Cord blood hematopoietic progenitor cells (CB-HPCs) transplanted immunodeficient NOD/LtsZ-scidIL2Rnull (NSG) and NOD/SCID/IL2Rnull (NOG) mice want efficient individual cell engraftment for long-term HIV-1 replication research. marker and microbial translocation after HIV-1 an infection. Humanized NSG mice reconstituted regarding to your brand-new process produced, moderate humoral and mobile immune system responses to HIV-1 postinfection. We think that NSG mice reconstituted regarding to your simple to use process will provide an improved in vivo model for HIV-1 replication and anti-HIV-1 therapy studies. Introduction Lately, efforts have already been designed to reconstitute an operating individual disease fighting capability in murine versions [1], [2]. Multilineage differentiation and self-renewal capability of Compact disc34+ cells have already been explored to reconstitute several sort of immunodeficient mice [3], [4], [5], [6], [7]. Third era, NOD-Rag1nullIL2Rnull, NOD/LtSz-scid/IL2Rnull ...
Acronyms and Abbreviations: AGM, aorta-gonad-mesonephros; BFU-E, burst-forming unit-erythroid; BFU-MK, burst-forming unit-megakaryocyte; CAFC, cobblestone area-forming cell; CAR, CXCL12-abundant reticular; CFC, colony-formingcell; CFU-E, colony-forming unit-erythroid; CFU-GM, colony-forming unit-granulocyte-macrophage; CFU-MK, colony-forming unit-megakaryocyte; CLP, common lymphoid progenitor; CMP, common myeloid progenitor; EBF, early B-cell factor; ECM, extracellular matrix; EGF, epidermal growth factor; EPO, erythropoietin; EPOR, erythropoietin receptor; FAK, focal adhesion kinase; FL, Flt-3 ligand; G-CSF, granulocyte colony-stimulating factor; G-CSF-R, granulocyte colony-stimulating factor receptor; GM-CSF, granulocyte-macrophage colony-stimulating factor; GM-CSF-R, granulocyte-monocyte colony-stimulating factor receptor; GMP, granulocyte-macrophage progenitor; HSC, hematopoietic stem cell; Ig, immunoglobulin; IL, interleukin; IRF4, interferon regulatory factor 4; LEF, lymphoid-enhancer ...
The 40-fold increase in childhood megakaryocyte-erythroid and B-cell leukemia in Down syndrome implicates trisomy 21 (T21) in perturbing fetal hematopoiesis. Here, we show that compared with primary disomic controls, primary T21 fetal liver (FL) hematopoietic stem cells (HSC) and megakaryocyte-erythroid progenitors are markedly increased, whereas granulocyte-macrophage progenitors are reduced. Commensurately, HSC and megakaryocyte-erythroid progenitors show higher clonogenicity, with increased megakaryocyte, megakaryocyte-erythroid, and replatable blast colonies. Biased megakaryocyte-erythroid-primed gene expression was detected as early as the HSC compartment. In lymphopoiesis, T21 FL lymphoid-primed multipotential progenitors and early lymphoid progenitor numbers are maintained, but there was a 10-fold reduction in committed PreproB-lymphoid progenitors and the functional B-cell potential of HSC and early lymphoid progenitor is severely impaired, in tandem with reduced early lymphoid gene expression.
Dysregulated hematopoiesis occurs in several chronic inflammatory diseases, but it remains unclear how hematopoietic stem cells (HSCs) in the bone marrow (BM) sense peripheral inflammation and contribute to tissue damage in arthritis. Here, we show the HSC gene expression program is biased toward myelopoiesis and differentiation skewed toward granulocyte-monocyte progenitors (GMP) during joint and intestinal inflammation in experimental spondyloarthritis (SpA). GM-CSF-receptor is increased on HSCs and multipotent progenitors, favoring a striking increase in myelopoiesis at the earliest hematopoietic stages. GMP accumulate in the BM in SpA and, unexpectedly, at extramedullary sites: in the inflamed joints and spleen. Furthermore, we show that GM-CSF promotes extramedullary myelopoiesis, tissue-toxic neutrophil accumulation in target organs, and GM-CSF prophylactic or therapeutic blockade substantially decreases SpA severity. Surprisingly, besides CD4+ T cells and innate lymphoid cells, mast cells are a
CFU-GM - Colony-Forming Unit-Granulocyte and Monocyte. Looking for abbreviations of CFU-GM? It is Colony-Forming Unit-Granulocyte and Monocyte. Colony-Forming Unit-Granulocyte and Monocyte listed as CFU-GM
The regulated lysosomal degradation pathway of autophagy prevents cellular damage and thus protects from malignant transformation. Autophagy is also required for the maturation of various hematopoietic lineages, namely the erythroid and lymphoid ones, yet its role in adult hematopoietic stem cells (HSCs) remained unexplored. While normal HSCs sustain life-long hematopoiesis, malignant transformation of HSCs or early progenitors leads to leukemia. Mechanisms protecting HSCs from cellular damage are therefore essential to prevent hematopoietic malignancies. By conditionally deleting the essential autophagy gene Atg7 in the hematopoietic system, we found that autophagy is required for the maintenance of true HSCs and therefore also of downstream hematopoietic progenitors. Loss of autophagy in HSCs leads to the expansion of a progenitor cell population in the bone marrow, giving rise to a severe, invasive myeloproliferation, which strongly resembles human acute myeloid leukemia (AML).
The latest market report published by Credence Research, Inc. Global Hematopoietic Stem Cells Transplantation Market - Growth, Share, Opportunities, Competitive Analysis, and Forecast, 2016 - 2022, the hematopoietic stem cells transplantation market was valued at USD 3,741.3 Mn in 2015, and is expected to reach USD 7,796.1 Mn by 2022, expanding at a CAGR of 10.6% from 2016 to 2022.. Market Insights. Over 50 years of studies in the field of blood-forming stem cells i.e. hematopoietic stem cells (HSC), researchers have developed significant understanding to use HSCs as a therapy. At present, no type of stem cell, adult, embryonic or fetal has attained such sufficient status. Hematopoietic stem cell transplantation (HSCT) is now routinely used for treating patients with malignant and non-malignant disorders of blood and the immune system. Currently, researchers have observed that through animal studies HSCs have the ability to form other cells such as blood vessels, muscles, and bone. Further ...
PURPOSE OF REVIEW: The hematopoietic stem cell niche is critical for the maintenance and proliferation of hematopoietic stem cells and, as such, is not only essential for steady-state hematopoiesis but may also be relevant to hematologic disease. The present review discusses recent advances in the understanding of interactions within the niche, its potential role in disease pathogenesis and models of its use as a therapeutic target. RECENT FINDINGS: Recent studies have continued to provide important insights into the cellular and molecular components constituting the hematopoietic stem cell niche. Niche interactions have been shown to be involved in the pathogenesis of hematologic disease in animal models. Molecular components of the niche involved in these interactions have been identified, and proof of principle that their manipulation can result in therapeutic benefit is available. Finally, pharmacologic manipulation of the niche is now being tested in stem cell-based therapies. SUMMARY: ...
Hematopoietic Stem Cells Transplantation (HSCT) Market report provides (6 Year Forecast 2020-2026) including detailed Coronavirus (COVID-19) impact analysis on Market Size, Regional and Country-Level Market Size, Segmentation Market Growth, Market Share, Competitive Landscape, Sales Analysis and Value Chain Optimization. This Hematopoietic Stem Cells Transplantation (HSCT) market competitive landscape offers details by topmost key manufactures (Kite Pharma, Thermo Fisher Scientific, CellGenix Technologie Transfer, Cesca Therapeutics, R&D Systems) including Company Overview, Company Total Revenue (Financials), Market Potential, Presence, Hematopoietic Stem Cells Transplantation (HSCT) industry Sales and Revenue Generated, Market Share, Price, Production Sites and Facilities, SWOT Analysis, Product Launch. For the period 2014-2020, this study provides the Hematopoietic Stem Cells Transplantation (HSCT) sales, revenue and market share for each player covered in this report.. Key Target Audience of ...
Looking for online definition of multipotential hemopoietic stem cell in the Medical Dictionary? multipotential hemopoietic stem cell explanation free. What is multipotential hemopoietic stem cell? Meaning of multipotential hemopoietic stem cell medical term. What does multipotential hemopoietic stem cell mean?
Many hematopoietic and nonhematopoietic diseases require chemotherapy and radiotherapy for treatment. Unfortunately, these regimens induce long-term damage, deleterious side effects and require multiple treatments for success. Hematopoietic stem cell (HSC) transplantation has proven effective in treatments but requires HLA-matching of these products to prevent complications, a process not easily achieved. Umbilical cord blood has become a standard in therapeutic transplantation primarily due to the ability to avoid more stringent HLA-matching. However, the low stem cell numbers in cord blood which limits use primarily in pediatric patients requires ex vivo expansion to increase patient availability. Clinical expansion is difficult to achieve and costly necessitating the need for enhanced protocols. The recent identification of inducing pluripotency by small molecule compounds has become an attractive option in HSC expansion. Our aim was to identify compounds that could induce self-renewal ...
The purpose of hematopoietic stem cell transplantation is to introduce blood producing cells from a normal donor. These cells can either provide what is missing in the body to the other cells, or can change the bodys immune response to the substances that have accumulated in the body. These normal hematopoietic stem cells can come from bone marrow, peripheral blood (i.e., the blood circulating in our bodys blood vessels) or umbilical cord blood (i.e., blood taken from the umbilical cord after a baby is born and umbilical cord is cut). The new donor cells repopulate the blood and bone marrow system and enter the organs of the body, including the brain. Wherever these cells go, they will produce the needed enzyme ...
Reprogramming of somatic cells to desired cell types holds great promise in regenerative medicine. However, production of transplantable hematopoietic stem cells (HSCs) in vitro by defined factors has not yet been achieved. Therefore, it is critical to fully understand the molecular mechanisms of HSC development in vivo. Here, we show that Fev, an ETS transcription factor, is a pivotal regulator of HSC development in vertebrates. In fev-deficient zebrafish embryos, the first definitive HSC population was compromised and fewer T cells were found in the thymus. Genetic and chemical analyses support a mechanism whereby Fev regulates HSC through direct regulation of ERK signaling. Blastula transplant assay demonstrates that Fev regulation of HSC development is cell autonomous. Experiments performed with purified cord blood show that fev is expressed and functions in primitive HSCs in humans, indicating its conserved role in higher vertebrates. Our data indicate that Fev-ERK signaling is essential for
The two most widely used sources of hematopoietic stem cells for allogeneic transplants in pediatric practice are bone marrow BM and cord blood CB. While bone marrow transplantation BMT is reaching its 30th year of application, human umbilical cord blood transplantation HUCBT is approaching its 10th. Although these procedures have basically the...
Seven cord blood (CB) units were tested for their capacity to repopulate irradiated NOD/SCID mice after one or two successive cryopreservation procedures. In primary transplants with frozen or refrozen CB cells we observed equivalent human colonies and percentages of human CD45+ cells, with multilineage engraftment. In secondary transplants flow cytometry and polymerase chain reaction for the a satellite region of chromosome 17 showed equivalent levels of human engraftment. Since CB units have, to date, mainly been stored in individual bags, our results suggest new options for optimizing the timing of infusions of expanded and non-expanded progenitors in transplants ...
Hematopoietic stem cell (HSC) transplantation can cure diverse diseases of the blood system, including hematologic malignancies, anemias, and autoimmune disorders. However, patients must undergo toxic conditioning regimens that use chemotherapy and/or radiation to eliminate host HSCs and enable donor HSC engraftment. Previous studies have shown that anti-c-Kit monoclonal antibodies deplete HSCs from bone marrow niches, allowing donor HSC engraftment in immunodeficient mice. We show that host HSC clearance is dependent on Fc-mediated antibody effector functions, and enhancing effector activity through blockade of CD47, a myeloid-specific immune checkpoint, extends anti-c-Kit conditioning to fully immunocompetent mice. The combined treatment leads to elimination of ,99% of host HSCs and robust multilineage blood reconstitution after HSC transplantation. This targeted conditioning regimen that uses only biologic agents has the potential to transform the practice of HSC transplantation and enable ...
What are they going to be? Hematopoietic stem cells under the microscope: New methods are helping the Helmholtz scientists to predict how they will develop.Credit: Helmholtz Zentrum München. Autonomous driving, automatic speech recognition, and the game Go: Deep Learning is generating more and more public awareness. Scientists at the Helmholtz Zentrum München and their partners at ETH Zurich and the Technical University of Munich (TUM) have now used it to determine the development of hematopoietic stem cells in advance. In Nature Methods they describe how their software predicts the future cell type based on microscopy images.. ...
Hematopoietic stem cells (HSC), which are generated within the aorta-gonad-mesonephros (AGM) region, are multipotent, myelo-lymphoid stem cell. These cells serve as a definitive source for hematopoietic cells that migrate and colonize the fetal liver (liver bud) at ~E10. Although controversy exists regarding the identity of the ancestor cell, there is evidence that these cells bud from endothelial cells of the ventral wall of the dorsal aorta ...
Expression of Thy-1 on hematopoietic cells from human fetal liver (FL), cord blood (CB), and bone marrow (BM) was studied with a novel anti-Thy-1 antibody, 5E10. Specificity of 5E10 for human Thy-1 was demonstrated by immunoprecipitation of a 25-35-kD molecule, and the sequence of a cDNA that was cloned by immunoselection of COS cells transfected with a cDNA library derived from a 5E10+ cell line. Two- and three-color immunofluorescence staining experiments revealed that the Thy-1 expression is restricted to, an average, 1-4% of FL, CB, and BM cells, and binding to these cell types is essentially restricted to a very small subset of lymphoid cells and approximately 25% of CD34+ cells. Thy-1+ CD34+ cells were further characterized as CD38lo/CD45RO+/CD45RA-/CD71lo/c-kit(lo) and rhodamine 123dull. When CD34+ cells were sorted on the basis of Thy-1 expression, the majority of clonogenic cells were recovered in the CD34+Thy-1- fraction, whereas the majority of cells capable of producing myeloid ...
TY - JOUR. T1 - Homeostatic regulation of hematopoiesis by the hematopoietic stem cell niche. AU - Takubo, Keiyo. PY - 2014/1/1. Y1 - 2014/1/1. UR - UR - M3 - Review article. C2 - 25675813. AN - SCOPUS:84925369130. VL - 86. SP - 755. EP - 765. JO - Seikagaku. The Journal of Japanese Biochemical Society. JF - Seikagaku. The Journal of Japanese Biochemical Society. SN - 0037-1017. IS - 6. ER - ...
UCLA Life Sciences Public Lecture: Bone Marrow Stem Cells: Developing New Therapies in the Fight Against Disease- Donald Kohn, January 18, 2011 Dr. Donald Kohn, UCLA professor of microbiology, immunology and molecular genetics, his research group at the Kohn Lab focus on developing new therapies for genetic diseases of the blood cells using gene therapy methods to correct hematopoietic stem cells. His laboratory performs studies on gene transfer, expression and immune response and then translates the findings into clinical trials. Read more from the original source:. Bone Marrow Stem Cells/Gene Therapy. ...
TY - JOUR. T1 - MTOR activation induces tumor suppressors that inhibit leukemogenesis and deplete hematopoietic stem cells after pten deletion. AU - Lee, Jae Y.. AU - Nakada, Daisuke. AU - Yilmaz, Omer H.. AU - Tothova, Zuzana. AU - Joseph, Nancy M.. AU - Lim, Megan S.. AU - Gilliland, D. Gary. AU - Morrison, Sean J.. PY - 2010/11/5. Y1 - 2010/11/5. N2 - Pten deficiency depletes hematopoietic stem cells (HSCs) but expands leukemia-initiating cells, and the mTOR inhibitor, rapamycin, blocks these effects. Understanding the opposite effects of mTOR activation on HSCs versus leukemia-initiating cells could improve antileukemia therapies. We found that the depletion of Pten-deficient HSCs was not caused by oxidative stress and could not be blocked by N-acetyl-cysteine. Instead, Pten deletion induced, and rapamycin attenuated, the expression of p16Ink4a and p53 in HSCs, and p19Arf and p53 in other hematopoietic cells. p53 suppressed leukemogenesis and promoted HSC depletion after Pten deletion. p16 ...
Bulgular: Otuz taze KK nitesinde her KK i in ortalama de erler: Toplam ekirdekli h cre say s (TNC): 93,8 30,1x107, CD34+: 3,85 2,55x106, ALDH+: 3,14 2,55 x106, CFU-GM: 2,64 1,96x105. On dokuz KK nitesinde donma zme sonras h cre de erleri: TNC: 32,79 17,27x107, CD34+: 2,18 3,17x106, ALDH+: 2,01 2,81x106, CFUGM: 0,74 0,92x105 dir. Bulgular m z; taze KK da TNC, CD34 ve ALDH; CFU-GM, CFU-GEMM ve BFU-E ile korelasyon g sterirken (TNC, r=0,47, r=0,35, r=0,41; CD34+, r=0,44, r=0,54 r=0,41; ve ALDH, r=0,63 r=0,45 r=0,6) donma zme sonras KK da korelasyon s ras yla CFU-GM, CFU-GEMM, ve BFU-E i in, TNC r=0,59, r=0,46, r=0,56, CD34+ r=0,67, r=0,48, r=0,61 ve ALDH r=0,61, r=0,67, r=0,67 olarak saptanm t r. B t n bulgular m z istatistiksel olarak anlaml km t r ...
Recurrent inactivating mutations have been identified in the X-linked plant homeodomain finger protein 6 (PHF6) gene, encoding a chromatin-binding transcriptional regulator protein, in various hematological malignancies. However, the role of PHF6 in normal hematopoiesis and its tumor-suppressor function remain largely unknown. We herein generated mice carrying a floxed Phf6 allele and inactivated Phf6 in hematopoietic cells at various developmental stages. The Phf6 deletion in embryos augmented the capacity of hematopoietic stem cells (HSCs) to proliferate in cultures and reconstitute hematopoiesis in recipient mice. The Phf6 deletion in neonates and adults revealed that cycling HSCs readily acquired an advantage in competitive repopulation upon the Phf6 deletion, whereas dormant HSCs only did so after serial transplantations. Phf6-deficient HSCs maintained an enhanced repopulating capacity during serial transplantations; however, they did not induce any hematological malignancies. ...
Everyone has a donor: contribution of the Chinese experience to global practice of haploidentical hematopoietic stem cell transplantation. Human blood cell substance (HLA)-matched donors for biological process vegetative cell transplantation (HSCT) have long been scarce in China. Haploidentical (haplo) donors are on the market for the overwhelming majority of patients, however toxicity has restricted this approach. 3 new approaches for haplo-HSCT originated from European country, China, and USA in 1990 and are developed to world-renowned system up to currently. The Chinese approach are greatly improved by implementing new personal acquisition regimens, donor choice supported non-HLA systems, risk-directed ways for graft-versus-host illness and relapse, and infection management. Haplo-HSCT has exhibited similar effectiveness to HLA-matched HSCT and has step by step become the predominant donor supply and therefore the 1st various donor alternative for allo-HSCT in China. Registry-based analyses ...
TY - JOUR. T1 - Distinct actions of interleukin-9 and interleukin-4 on a hematopoietic stem cell line, EMLC1. AU - Wang, Xin Yuan. AU - Gelfanov, Vasily. AU - Sun, Hui Bin. AU - Tsai, Schickwann. AU - Yang, Yu Chung. N1 - Funding Information: This work is supported by United States Public Health Service Grants R01DK50570 and R01HL48819 (to Y.-C.Y). PY - 1999/1. Y1 - 1999/1. N2 - EMLC1 is a hematopoietic stem cell line that depends on stem cell factor (SCF) for growth and generates lymphoid, erythroid and myeloid progenitors in the presence of different cytokines. We have studied signaling events leading to cell proliferation and differentiation of EMLC1 mediated by interleukin (IL)-4 and IL-9. It was found that IL-9 enhances SCF-induced cell proliferation and promotes erythropoietin (EPO)-dependent erythroid differentiation of EMLC1 cells. However, IL-9 alone cannot support the growth of this cell line. In contrast, IL-4 by itself is sufficient to promote the growth of EMLC1 cells, even in the ...
Myeloid leukemia (ML) is one of the major health concerns from exposure to radiation. However, the risk assessment for developing ML after exposure to space radiation remains uncertain. To reduce the uncertainty in risk prediction for ML, a much increased understanding of space radiation-induced changes in the target cells, i.e., hematopoietic stem/progenitor cells (HSPCs), is critically important. We used the label-free quantitative mass spectrometry (LFQMS) proteomic approach to determine the expression of protein in HSPC-derived myeloid colonies obtained at an early time-point (one week) and a late time-point (six months) after an acute whole body exposure of CBA/CaJ mice to a total dose of 0, 0.1, 0.25, or 0.5 Gy of heavy-ion titanium (48Ti ions), which are the important component of radiation found in the space environment. Mice exposed to 0 Gy of 48Ti ions served as non-irradiated sham controls. There were five mice per treatment groups at each harvest time. The Trans-Proteomic Pipeline ...
phdthesis{0c477139-a4a1-40fc-a0da-8d695c46f4cb, abstract = {The possibility to manufacture hematopoietic stem cells (HSCs) in the laboratory would provide an indefinite source of cells for patients requiring bone marrow transplantation. Moreover, combined with the progress in gene editing techniques, it would provide a novel platform for gene and cell replacement therapies for a range of currently incurable congenic and acquired disorders. During my PhD, I worked with an optimized protocol for in vitro blood generation from human Pluripotent Stem Cells (hPSCs). It was designed to mimic human hematopoietic development, and allowed us to explore some aspects that could elicit in vitro generation of HSCs. Using single-cell transcriptional analysis, we could explore the gene expression dynamics driving the endothelial-to-hematopoietic transition that occurs during in vitro differentiation. We also used this platform to explore the role of adrenergic signaling in human hematopoietic development, and ...
Kamimae-Lanning, A. Programming of the Fetal Hematopoietic Stem and Progenitor Cell Compartment (2013). OHSU Digital Collections. ...
We studied the adhesion of primitive and committed progenitors from chronic myelogenous leukemia (CML) and normal bone marrow to stroma and to several extracellular matrix components. In contrast to benign primitive progenitors from CML or normal bone marrow, Ph1-positive primitive progenitors from CML bone marrow fail to adhere to normal stromal layers and to fibronectin and its proteolytic fragments, but do adhere to collagen type IV, an extracellular matrix component of basement membranes. Similarly, multilineage colony-forming unit (CFU-MIX) progenitors from CML bone marrow do not adhere to fibronectin or its adhesion promoting fragments but adhere to collagen type IV. Unlike committed progenitors from normal bone marrow, CML single-lineage burst-forming units-erythroid and granulocyte/macrophage colony-forming units fail to adhere to fibronectin or its components but do adhere to both collagen type IV and laminin. Evaluation of adhesion receptor expression demonstrates that fibronectin ...

No data available that match "hematopoietic stem cells"

  • We have adapted various tools for characterization of the metabolic properties of hematopoietic stem cells (HSCs). (
  • Hematopoietic progenitor cells (HPCs) or hematopoietic stem cells (HSCs) are cells present in blood and bone marrow. (
  • While investigators in a number of laboratories have documented that the hematopoietic stem cells (HSCs) of fetal and adult mice are CD38 + , no information is available about CD38 expression by HSCs of newborn and juvenile mice. (
  • However, the majority of HSCs of 5-week-old mice became CD38 + following injection of 5-fluorouracil, indicating that activation of juvenile stem cells enhances CD38 expression. (
  • Characterization of the surface phenotypes of hematopoietic stem cells (HSCs) and development of techniques for their purification are important subjects in stem cell transplantation and gene therapy. (
  • In autologous situations, transplantation of HSCs that are free of tumor cells may reduce the risk of recurrence of malignancies. (
  • Here, we determined that aging of endothelial cells (ECs), a critical component of the BM microenvironment, was sufficient to drive hematopoietic aging phenotypes in young HSCs. (
  • We used an ex vivo hematopoietic stem and progenitor cell/EC (HSPC/EC) coculture system as well as in vivo EC infusions following myelosuppressive injury in mice to demonstrate that aged ECs impair the repopulating activity of young HSCs and impart a myeloid bias. (
  • Within this course we will study how hematopoietic stem cells (HSCs) are generated during embryogenesis and development, and how we can make HSCs from embryonic stem cells or induced pluripotent stem cells. (
  • We will study the molecular mechanisms that underlie the self-renewal properties of HSCs, and which molecular mechanisms drive differentiation of HSCs towards mature erythrocytes, blood platelets and innate or adaptive immune cells. (
  • Hematopoietic stem cells (HSCs) are the stem cells that give rise to other blood cells. (
  • The definition of hematopoietic stem cell has developed since HSCs were first discovered in 1961. (
  • Hematopoietic stem cells (HSCs) give rise to all blood cell types including myeloid and lymphoid lineages. (
  • T lymphocytes develop in the thymus from bone-marrow derived hematopoietic stem (HSCs) and progenitor cells (HSPCs). (
  • Dexter observed that mesenchymal stromal cells could maintain early HSCs ex vivo, and both Lord and Gong showed that these cells localized to the endosteal margins in long bones. (
  • Definitive HSCs derived during embryogenesis in the aorta-gonad-mesonephros region subsequently colonize fetal and adult haematopoietic organs. (
  • HSCs comprise a self-renewing population of cells with the capacity to differentiate into all classes of differentiated blood cells. (
  • Clinically, HSCs are used to reconstitute the hematopoeitic systems of individuals undergoing blood and marrow transplants. (
  • However, both steps are critical in the case of primary cells, such as the hematopoietic stem cells (HSCs). (
  • HSCs are a rare cell population present in the bone marrow (BM) of higher mammals, and it is the responsible for the maintenance and replenishment of all hematopoietic cells for the lifespan of the animals by means of two fundamental properties: self-renewal and multipotency. (
  • Adult hematopoietic stem cells (HSCs) are a rare population of cells that are present in the bone marrow (BM) and are the responsible for the generation of all mature blood cells, including erythrocytes, platelets, and immune cells ( 1 ). (
  • Recent data have suggested that human CD34 − hematopoietic stem cells (HSCs) exist, challenging the concept that HSCs necessarily and exclusively express the CD34 antigen. (
  • In mice, quiescent HSCs have been shown to be mostly CD34 − , but as a consequence of 5-fluorouracil treatment or cytokine stimulation, differentiate into CD34 + cells. (
  • Using a semiquantitative reverse transcription-polymerase chain reaction, one of the ATP-binding cassette (ABC) transporters, the breast cancer resistance protein (Bcrp) or ABC transporter G2 (ABCG2), was found to be highly expressed in SP cells as well as other primitive HSCs and to sharply drop with hematopoietic differentiation. (
  • The isolation of Bcrp/ABCG2 + cells appears to be an attractive tool to analyze and characterize HSCs, and may eventually allow for the purification of these cells for clinical purposes. (
  • Hematopoietic stem cells (HSCs) have the potential for self-renewal and differentiation into all lineages of blood cells. (
  • Transplantation studies with injection of HSCs into myeloablated recipients allow for the analysis of the presence of donor cells and their capacity to proliferate and repopulate, thereby indicating HSC activity [ 1 ]. (
  • In these animal models, murine HSCs have been demonstrated to be negative for lineage markers (Lin − ), including myeloid and B and T cell lineages, and positive for c-kit, Sca-1, and CD34 [ 1 - 5 ]. (
  • EMH activation requires hematopoietic stem cell (HSC) proliferation and mobilization, processes that depend upon estrogen receptor α (ERα) in HSCs. (
  • Blood cells are produced by the proliferation and differentiation of a very small population of pluripotent hematopoietic stem cells (HSCs) that also have the ability to replenish themselves by self-renewal (Figure 1). (
  • During differentiation, the progeny of HSCs progress through various intermediate maturational stages, generating multi-potential and lineage-committed progenitor cells prior to reaching maturity. (
  • The hematopoietic potential of mouse HSCs is assayed by injection into mice in which hematopoiesis has been suppressed by irradiation or other methods, and measuring the repopulation of the recipient BM, blood, spleen and/or thymus with donorderived cells after a period of at least 4 months. (
  • The aim of the meeting is to bring together recognised experts and outstanding young team leaders around the central theme of hematopoietic stem cells (HSCs) production and regulation throughout life. (
  • It will be essential to generate new hypotheses and to move forwards our understanding of HSCs, the key cell type for the continuous production of blood cells throughout life. (
  • Derived from the Greek word for blood (αιμα, haima ), hematopoiesis describes the generation of fully differentiated effector blood cells from multipotential, self-renewing hematopoietic stem cells (HSCs). (
  • 5 The definitive hematopoietic wave expands in the fetal liver (FL) from approximately E11.5, but HSCs are produced before this time in the ventral wall of the dorsal aorta and YS. (
  • A group of researchers at Osaka University revealed that ESAM (Endothelial cell-selective adhesion molecule), a surface marker for hematopoietic stem cells (HSCs) and vascular endothelial cells (ECs), played an important role in the ontogeny of hematopoiesis in mice, particularly in the development of adult-type erythropoiesis. (
  • In hematopoiesis, a process essential for growth and life maintenance for mammals, HSCs give rise to other blood cells for the organism's entire life. (
  • The microenvironment in bone marrow provides signals that regulate and support the production of blood cells necessary to maintain homeostasis of HSCs. (
  • In HSCs co-cultured with a murine stromal cell line, ESAM-null HSCs exhibited functional disruption of differentiation into adult-type blood cells. (
  • The lab grown HSCs were then transplanted as single cells with their daughter cells into mice whose marrow had been destroyed by irradiation. (
  • This was done to see whether the transplanted HSCs could self-renew and produce healthy blood cells. (
  • Interestingly, the same team had earlier published their research where they demonstrated that it was possible to generate functional HSCs from adult vascular endothelial cells. (
  • What are Hematopoietic Stem Cells (HSCs)? (
  • They have to be constantly replenished and this is where the HSCs step in and maintain adequate blood cell counts for the normal health and well-being of the individual. (
  • In addition to the production of mature blood cells, the HSCs have a unique property. (
  • They can self-renew and form more of their kind such that a few thousand functional HSCs can ensure an adequate supply of all the blood cells that one needs. (
  • The team also found that specialized types of endothelial cells provide a suitable nurturing environment for the HSCs, termed the 'vascular niche' and these cells are referred to as vascular niche cells. (
  • Aging is associated with changes in the hematopoietic system, including cell-intrinsic alterations of hematopoietic stem cells (HSCs), leading to a decline in HSC self-renewal, immune system dysregulation, and predisposition to myeloid neoplasms. (
  • Hematopoietic stem cells (HSCs) are unique in their ability to migrate to various sites, ensuring the safety and integrity of their regenerative potential. (
  • A simple intravenous infusion of HSCs/progeniors can reconstitute the BM hematopoietic reservoir after myeloablative therapy, significantly improving the clinical outcome of patients with a variety of diseases, especially in Oncology. (
  • In addition, recent reports point to a third hematopoietic site, the allantoic mesoderm of the placenta, generating autonomously in situ a large pool of pluripotent HSCs in the mouse embryo between E8.5 and E9.5 (Alvarez-Silva et al. (
  • For example, the site of initiation of definitive HSCs has been identified as a cluster of cells between the dorsal aorta and the posterior cardinal vein, anatomically homologous to the AGM region of mammals (Zhang and Rodaway, 2007 ). (
  • The zebrafish AGM HSCs migrate to the caudal hematopoietic tissue (CHT) that mirrors the functions of both fetal liver and placenta in mammals, providing transient niche to support definitive HSC expansion and differentiation. (
  • Rapidly cycling fetal and neonatal hematopoietic stem cells (HSCs) generate a pool of quiescent adult HSCs after establishing hematopoiesis in the bone marrow. (
  • We recently discovered that PTPsigma is also expressed by hematopoietic stem cells (HSCs). (
  • Hematopoietic stem cells (HSCs) are thought to reside in discrete niches through stable adhesion, yet previous studies have suggested that host HSCs can be replaced by transplanted donor HSCs, even in the absence of cytoreductive conditioning. (
  • To explain this apparent paradox, we calculated, through cell surface phenotyping and transplantation of unfractionated blood, that ∼1-5% of the total pool of HSCs enters into the circulation each day. (
  • Bromodeoxyuridine (BrdU) feeding experiments demonstrated that HSCs in the peripheral blood incorporate BrdU at the same rate as do HSCs in the bone marrow, suggesting that egress from the bone marrow to the blood can occur without cell division and can leave behind vacant HSC niches. (
  • Through these interactions, HSCs can be assured of receiving the appropriate supportive signals that allow them to retain their stem cell identity. (
  • CD8 + /TCR − facilitating cells (FCs) have been shown to enhance engraftment of hematopoietic stem cells (HSCs) in allogeneic recipients without causing GVHD. (
  • In adult mammals, hematopoietic stem cells (HSCs) reside in the bone marrow (BM) and are maintained in a quiescent and undifferentiated state through adhesive interactions with specialized microenvironmental niches. (
  • Here, we show that HSCs adhere to JAM-B expressed by BM stromal cells in a JAM-C dependent manner. (
  • The interaction regulates the interplay between HSCs and BM stromal cells as illustrated by the decreased pool of quiescent HSCs observed in jam-b deficient mice. (
  • 10 Recently, expression of several JAM family members, such as JAM-A, JAM-C, JAM4, or ESAM, has been reported in hematopoietic stem cells (HSCs), although a function for these proteins in hematopoiesis remains unknown. (
  • In adult mammals, HSCs are rare cells mainly located in the bone marrow (BM) and able to generate all mature blood cells. (
  • A small population of primitive hematopoietic stem cells (HSCs) is present in the bone marrow. (
  • The CD34 + protein is a surface glycoprotein expressed on HSCs and progenitor cells in early developmental stages in HUCB and bone marrow, as well as on endothelial cells. (
  • Haematopoietic stem cells (HSCs) are tissue-specific stem cells that replenish all mature blood lineages during the lifetime of an individual. (
  • Although Notch signaling is not essential for homeostasis of adult hematopoietic stem cells (HSCs), Notch-ligand adhesive interaction maintains HSC quiescence and niche retention. (
  • Hematopoietic stem cells (HSCs) can either self-renew or differentiate into various types of cells of the blood lineage. (
  • Hematopoietic stem cells (HSCs) constitute a rare cell population that can either self-renew or differentiate into various types of mature blood cells. (
  • Here, we show that red pulp vascular cell adhesion molecule 1 (VCAM-1)+ macrophages are essential to extramedullary myelopoiesis because these macrophages use the adhesion molecule VCAM-1 to retain HSCs in the spleen. (
  • Hematopoietic stem cells (HSCs) have the capacity to maintain or reconstitute an organism's immune system for life. (
  • Due to limited supply of these rare cells, the generation of HSCs de novo from readily available cell sources has been a central goal in synthetic immunology. (
  • First, developmental mimicking attempts to generate HSCs from pluripotent stem cells (PSCs) by recapitulating the embryonic developmental steps towards HSCs in vitro through temporally controlled exposure to signaling factors and inhibitors. (
  • Third, combinatorial transcription factor-mediated transdifferentiation employs forced expression of transcriptional master regulators with known roles in HSCs to convert somatic cells to HSCs. (
  • Other studies have shown that AFT024 is a potent supporter of human hematopoietic stem cells ( 9 - 11 ). (
  • The goal of this study was to elucidate the extent to which cells of the hematopoietic system, particularly human hematopoietic stem cells (HSC), were affected by mobile phone radiation. (
  • Marker Found that Enables Segregation of True Human Hematopoietic Stem Cells. (
  • Developed to promote the optimal expansion of human hematopoietic stem cells (HSC) from bone marrow, mobilized peripheral blood, and cord blood, Stemline Hematopoietic Stem Cell Expansion Medium demonstrates higher total nucleated cell (TNC) fold increases than other commercially available serum-free media formulations. (
  • Identification and enumeration of human hematopoietic stem cells remain problematic, since in vitro and in vivo stem cell assays have different outcomes. (
  • of stem cell therapy called autologous (self) hematopoietic stem cell transplant. (
  • This type of treatment is called a bone marrow or stem cell transplant. (
  • Here is a list of diseases for which stem cell transplant may be an option. (
  • The second edition is fully revised and includes new chapters on microbiome, metabolism, kinase targets, micro-RNA and mRNA regulatory mechanisms, signaling pathways in GVHD, innate lymphoid system development, recovery and function in GVHD, genetically engineered T-cell therapies, immune system engagers for GVHD and graft-versus-tumor, and hematopoietic cell transplant for tolerance induction in solid organ grafts. (
  • Children or adults with aplastic anemia have lost their stem cells after birth and may not require such high doses of chemotherapy and irradiation prior to a transplant. (
  • 12 12 Stem Cell Transplant and Cellular Therapy Unit, University Hospital, Siena, Italy. (
  • There are no evaluations for Hematopoietic Stem Cell Transplant. (
  • Up to 4.3 years after transplant, HIV DNA was not detected in the blood and rectal tissue among two patients with HIV who underwent hematopoietic stem cell transplantation for cancer, researchers reported at the 2013 International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention in Kuala Lumpur, Malaysia. (
  • Our hematopoietic stem cell transplant research team participates in collaborative studies through the following consortiums: the Children's Oncology Group (COG) , the Blood and Marrow Transplant Clinical Trials Network , and the Pediatric Blood and Marrow Transplant Consortium in order to help move the field of pediatric transplantation forward. (
  • Using fludarabine to reduce exposure to aklylating agents in children with sickle cell disease receiving busulfan, cyclophosphamide, and antithymocyte globulin transplant conditioning: Results of a dose de-escalation trail. (
  • Epidermolysis bullosa patients treated per study regimen with chemotherapy and stem cell transplant. (
  • The purpose of this study is to find out if a stem cell transplant is safe for patients with a very rare disease. (
  • Hematopoietic cell transplant (HCT) is increasingly used as a treatment for various malignant and non-malignant disease processes. (
  • Considering taking medication to treat conditioning+prior+to+allogeneic+hematopoietic+stem+cell+transplant? (
  • Below is a list of common medications used to treat or reduce the symptoms of conditioning+prior+to+allogeneic+hematopoietic+stem+cell+transplant. (
  • If the transplant is successful, new bone marrow cells will produce healthy red blood cells, white blood cells, and platelets. (
  • In order for the transplant to be successful, certain markers on the blood cells and bone marrow cells must match. (
  • Sarah McInerney (40) has obtained chemotherapy and a stem cell transplant, which is not available in Ireland to treat progressive Multiple Sclerosis. (
  • Transplant of engineered functional hematopoietic stem cells can potentially yield a lifelong supply of healthy blood cells to cure several diseases. (
  • Similarly, using a lethal irradiation and transplant model, co-infusion of young ECs with whole BM (WBM) cells from young or old donors improved HSC-repopulating activity, engraftment, and survival in recipient mice compared with infusions of donor WBM cells alone. (
  • Finally, Dr. George does not discuss an important subset of oncology patients, those undergoing hematopoietic stem cell transplant. (
  • Mature donor T-cells present in the transplant facilitate T-cell reconstitution but also induce GVHD, which itself impairs immune reconstitution. (
  • Hematopoietic stem cell transplantation ( HSCT ) is the transplantation of multipotent hematopoietic stem cells , usually derived from bone marrow, peripheral blood, or umbilical cord blood. (
  • Autologous HSCT requires the extraction ( apheresis ) of haematopoietic stem cells (HSC) from the patient and storage of the harvested cells in a freezer. (
  • The spectrum of target antigens associated with tumor immunity and alloimmunity after allogeneic HSCT: Host-derived T and B cells can be induced to recognize tumor-associated antigens, whereas donor-derived B and T cells can recognize both tumor-associated antigens and alloantigens. (
  • It is important to note, however, that while the United States Food and Drug Administration (FDA) have approved hematopoietic stem cell transplantation (HSCT) for use against cancer , it is not yet approved for wider use. (
  • Allogeneic HSCT requires a donor to supply suitable stem cells. (
  • Autologous HSCT avoids the issue of trying to find a matching donor because stem cells are harvested from the patients themselves. (
  • Increasing rate of incidence is in turn, expected to increase the demand for hematopoietic stem cell transplantation thus, propelling growth of the hematopoietic stem cell transplantation (HSCT) market. (
  • A collaborative research study on hematopoietic stem cell transplantation initiated by World Network for Blood and Marrow Transplantation (WBMN) in 2013 in the domain of promotion of access to hematopoietic stem cell transplantation, developed a donation guidance document, technical and scientific input on safety, and quality of HSCT as mentioned in annual report of the WBMN. (
  • Therefore, the aim of this study was to assess the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for the management of AML with GS. (
  • However, the optimal therapeutic strategy for GS remains unclear, especially in regards to the indications for need of allogeneic hematopoietic stem cell transplantation (allo-HSCT). (
  • This study included all consecutive adult AML aged over 15 years, excluding patients with acute promyelocytic leukemia, who underwent allo-HSCT for the first time between January 2000 and December 2008 at the nine institutions participating in the Kanto Study Group for Cell Therapy. (
  • This two (2) day program is designed for Registered Nurses and Nurse Practitioners caring for patients undergoing Hematopoietic Stem Cell Transplantation (HSCT). (
  • Hematopoietic stem cell transplantation (HSCT) or Bone marrow transplantation is a medical procedure in the field of hematology and oncology that involves transplantation of hematopoietic stem cells (HSC). (
  • Autologous HSCT involves isolation of HSC from a patient, storage of the stem cells in a freezer, high-dose chemotherapy to eradicate the malignant cell population at the cost of also eliminating the patient's bone marrow stem cells, then return of the patient's own stored stem cells to their body. (
  • Nutritional status is an important factor influencing outcomes in persons undergoing hematopoietic stem cell transplantation (HSCT). (
  • Histocompatible hematopoietic stem cell transplantation (HSCT) was conducted on a 4.5-year-old girl with Niemann-Pick disease type B. The donor was her unaffected brother. (
  • To provide an overview of recently published work on autologous hematopoietic stem-cell transplantation (HSCT) in patients with systemic sclerosis (SSc). (
  • HSCT involves the intravenous (IV) infusion of autologous or allogeneic stem cells to re-establish hematopoietic function in patients whose bone marrow or immune system is damaged or defective. (
  • Hematopoietic stem cell transplantation (HSCT) is an established therapeutic procedure for several congenital and acquired disorders, both malignant and nonmalignant. (
  • Background and Objectives Hematopoietic stem cell transplantation (HSCT) is a complex and expensive procedure. (
  • Hematopoietic stem cell transplantation (HSCT) is considered the treatment of choice for many patients with severe malignant or non-malignant, acquired or congenital disorders of the hematopoietic system or with chemosensitive, radiosensitive or immunosensitive tumors. (
  • Despite the availability of new antifungal compounds, invasive fungal infection remains a significant cause of morbidity and mortality in children and adults undergoing allogeneic hematopoietic stem cell transplantation (HSCT). (
  • 4.8 If haematopoietic stem cell transplantation (HSCT) is urgent and there are no suitable available donors, assess risk and liaise with the registry. (
  • Over the past decade, advances in hematopoietic stem cell transplantation (HSCT) have enabled older individuals to undergo the procedure as well as to serve as donors. (
  • In the setting of allogeneic HSCT, ARCH present in the donor may contribute to adverse outcomes such as unexplained cytopenias posttransplant and donor cell leukemia. (
  • A better understanding of the hematopoietic milieu of HSCT recipients and of the importance of ARCH in the context of the replicative pressures imposed on transplanted HSPCs is needed in order to optimize conditioning regimens, donor selection and clinical outcomes post-HSCT. (
  • Allogeneic hematopoietic stem cell transplantation (HSCT) reverses the bone marrow failure syndrome due to GATA2 deficiency. (
  • The most common indications for HSCT are blood cancers, mainly acute leukaemia, cancers of the lymphatic tissues (lymphomas) and the antibody-forming blood cells (multiple myeloma). (
  • HSCT can be broadly divided into autologous transplantation, where patients use their own blood stem cells, and allogeneic transplantation, where stem cells are obtained from a different person. (
  • We now propose a clinical trial to test whether donor lymphocytes infusion (DLI) using TK-transduced cells permits to induce a graft-versus-tumor (GVT) effect for treatment of relapse after HSCT, while GVHD can be controlled by GCV treatment. (
  • The hematopoietic microenvironment provides a complex molecular milieu that regulates the self-renewal and differentiation activities of stem cells. (
  • The fundamental property shared by all stem cells is an ability to balance the cell fate decision of self-renewal vs. differentiation. (
  • Traditionally, it was held that the differentiation potential of somatic stem cells is limited to their tissue of origin. (
  • The invention provides means of manipulating hematopoietic stem cell differentiation by modulation of levels of NR2F6 (EAR2). (
  • Provided are compositions of matter, protocols and methods of use by which inhibiting expression of NR2F6 or activity thereof promotes differentiation of selective hematopoietic lineages, or conversely overexpression of NR2F6 or activity thereof inhibits differentiation. (
  • In one embodiment inhibition of differentiation is performed in other cell lineages besides hematopoietic. (
  • The OP9-DL1 culture system utilizes fetal calf serum and thus contributes to variable efficiencies in T-cell differentiation and moreover suffers from low maturation rates. (
  • Recently, a new serum-free artificial thymic organoid (ATO) system was developed that supports highly efficient and reproducible in vitro differentiation and positive selection of human T-cells from multiple sources of HSPCs, including cord blood, bone marrow and peripheral blood CD34+ HSPCs. (
  • This event requires a special environment, termed the hematopoietic stem cell niche, which provides the protection and signals necessary to carry out the differentiation of cells from HSC progenitors. (
  • Hematopoiesis involves a series of differentiation steps from one progenitor cell to a more committed cell type, forming the recognizable tree seen in the adjacent diagram. (
  • In murine embryonic stem cell differentiation assays, PGE2 caused amplification of multipotent progenitors. (
  • Starting from fundamental principles in hematopoiesis, Advances in Hematopoietic Stem Cell Research assemble a wealth of information relevant to central mechanisms that may regulate differentiation, and expansion of hematopoietic stem cells in normal conditions and during disease. (
  • This paracrine signalling causes stem cells to head down a differentiation pathway as you have experienced. (
  • This review provides an overview of the current status of HSPC research with a focus on (i) assays used to detect and enumerate human and mouse stem and progenitor cells, (ii) phenotypic markers and methods used for their identification and isolation, and (iii) culture systems used to amplify stem and progenitor cells or to promote their differentiation in order to produce large numbers of mature blood cells for transfusion. (
  • StemSpan™ SFEM II (Catalog #09605) is an improved version of StemSpan™ SFEM that is further enriched to promote and support higher rates of CD34+ expansion and/or cell differentiation. (
  • S tem cells are a primitive cell type found in all animals and are capable of both self-renewal and differentiation. (
  • It is this capacity for self-renewal and for differentiation into repair cells that offers great potential for regenerative medicine. (
  • This subset has 4-fold higher proliferation rates than CCR2−CD150+CD48− LSK cells, displays a myeloid differentiation bias, and dominates the migratory HSPC population. (
  • The proliferation and differentiation of cells is controlled by a group of hematopoietic growth factors. (
  • Growth factors and miRNA regulating differentiation of hematopoietic stem cells (HSC) to various blood-related cell types. (
  • NF-κB is another known factor that controls cell fate, survival, and differentiation ( 4 , 5 ). (
  • Second, HSC development from PSCs is recapitulated randomly inside a forming teratoma in vivo , and hematopoietic differentiation can be enhanced and directed using hematopoietic stromal cells and cytokines. (
  • Chadwick K, Wang L, Li L et al (2003) Cytokines and BMP-4 promote hematopoietic differentiation of human embryonic stem cells. (
  • Cell stress regulation driving resident progenitor cell function: a potential pan-stem cell mechanism? (
  • Many human blood cells, such as red blood cells (RBCs), immune cells, and even platelets all originate from the same progenitor cell, the hematopoietic stem cell (HSC). (
  • The CMP can then further differentiate into the megakaryocyte-erythroid progenitor cell (MEP), which goes on to make RBCs and platelets, or the granulocyte/macrophage progenitor (GMP), which gives rise to the granulocytes of the innate immune response. (
  • The hemangioblast theory, which posits that the RBCs and ECs derive from a common progenitor cell, was developed as researchers observed that receptor knockout mice, such as Flk1-/-, exhibited defective RBC formation and vessel growth. (
  • Ablation of conventional DCs (cDCs) results in hematopoietic stem/progenitor cell (HSPC) mobilization that was greater than that seen with ablation of bone marrow macrophages, and cDC ablation also synergizes with granulocyte-colony stimulating factor to mobilize HSPCs. (
  • The current standard protocol for hematopoietic stem and progenitor cell mobilization involves multi-day injections of granulocyte-colony stimulating factor (G-CSF). (
  • A) Schematic of hematopoietic development focusing on the circulating blood cell types and FL progenitor cell types assayed in our E14.5 screen. (
  • We elected to screen the blood and FL at E14.5 so as to gain access to primitive and definitive blood cells (∼ 50:50 mix), and all definitive progenitor cell types. (
  • Poulos and colleagues used murine ex vivo hematopoietic stem and progenitor cell (HSPC)/EC coculture and in vivo EC infusion models to study the impact of ECs on hematopoietic system aging. (
  • This report focuses on the development of an integrated system for the use of one specific type of stem cell, the hematopoietic progenitor cell (HPC), which is a multipotent stem cell responsible for the continual production of the diverse array of normal blood cells. (
  • Throughout this report the committee uses the term hematopoietic progenitor cell and the abbreviation HPC to avoid confusion with other forms or sources of stem cells. (
  • For umbilical cord transplantation, see TRANS.00016 Umbilical Cord Blood Progenitor Cell Collection, Storage and Transplantation for additional information and criteria. (
  • Adapted from an open access image attributed to ZooFari and Mikael Häggström ( ) and augmented from literature and NHLBI Progenitor Cell Biology Consortium (PCBC) collaborators. (
  • Caution is clearly required for non HSC/HPC stem/progenitor cell uses of CB, based on insufficient biological and preclinical information for MSC, EPC, and iPSC. (
  • The patient's own stored stem cells are then transfused into his/her bloodstream, where they replace destroyed tissue and resume the patient's normal blood cell production. (
  • The investigational therapy involved infusion of autologous CD34+ cells transduced with the elivaldogene tavalentivec (Lenti-D) lentiviral vector. (
  • This review is intended as a basic overview of allogeneic and autologous stem cell transplantation with a special focus on long-term follow-up issues relevant to primary care providers. (
  • Stem cell transplantation can be performed with cells from a family member or an unrelated volunteer (allogeneic transplantation) or with stem cells previously collected from the patient (autologous transplantation). (
  • These patients include those requiring autologous and allogeneic stem cell transplants, regardless of the stem cell source. (
  • Autologous transplantation, using the patient's own stem and progenitor cells, has also been found to effectively treat specific disorders, e.g., lymphomas and myelomas, and has been employed as a therapy for other malignancies when allogeneic stem cell transplantation is not possible. (
  • Lack of persistent remission following initial recovery in patients with type 1 diabetes treated with autologous peripheral blood stem cell transplantation. (
  • To assess metabolic control in patients with newly diagnosed type 1 diabetes mellitus who underwent immunoablation followed by autologous peripheral blood stem cell transplantation (APBSCT) as a treat. (
  • Autologous stem cell transplantation is considered investigational and not medically necessary for individuals with AML. (
  • Despite use of newer approaches, some patients being considered for autologous hematopoietic cell transplantation (HCT) may only mobilize limited numbers of hematopoietic progenitor cells (HPCs) into blood, precluding use of the procedure, or being placed at increased risk of complications due to slow hematopoietic reconstitution. (
  • 1 The vast majority of clinical autologous HCT procedures utilize hematopoietic progenitor cells (HPCs) mobilized into the blood. (
  • The Hematopoiesis and Hematopoietic Stem Cell Biology program focuses on understanding the basic cellular and molecular mechanisms underlying the production and function of blood cells in health and disease. (
  • Major areas of interest include the basic mechanisms involved in regulating the production and terminal development of blood cells, referred to as hematopoiesis. (
  • however, the best characterized stem cells are those responsible for hematopoiesis ( 2 ). (
  • These cultured stem cells retain the ability to regenerate in vivo hematopoiesis after transplantation in a manner that is indistinguishable from their freshly purified counterparts ( 7 ). (
  • In vertebrates, the vast majority of hematopoiesis occurs in the bone marrow and is derived from a limited number of hematopoietic stem cells that are multipotent and capable of extensive self-renewal. (
  • Through the process of hematopoiesis, all cellular blood components are derived from hematopoietic stem cells. (
  • In Genetic Modification of Hematopoietic Stem Cells: Methods and Protocols , leading scientists in the field provide a compendium of protocols which cover the subject comprehensively, from the purification and culture of various types of hematopoietic cells for subsequent genetic modification by vector development and technical issues of small and large scale vector production, to the complex issue of monitoring and biosafety studies related to gene-modified hematopoiesis. (
  • There are 2 types of hematopoiesis that occur in humans: Primitive hematopoiesis - blood stem cells differentiate into only a few specialized blood lineages (typically isolated to early fetal development). (
  • The pioneering work of Till and McCulloch in 1961 experimentally confirmed the development of blood cells from a single precursor hematopoietic stem cell (HSC), creating the framework for the field of hematopoiesis to be studied over the following decades. (
  • A resident population of dendritic cells (DCs) has been identified in murine bone marrow, but its contribution to the regulation of hematopoiesis and establishment of the stem cell niche is largely unknown. (
  • The stem cells are then able to travel or "home" to the bone marrow cavity to re-establish hematopoiesis over the next 2 weeks. (
  • Bone marrow (BM) is the major site of hematopoiesis in humans and, under normal conditions, only small numbers of hematopoietic stem and progenitor cells (HSPCs) can be found in the peripheral blood (PB). (
  • 1, 2 Various assay formats have been developed that differ in the choice of donor and host mouse strains, the method to ablate or suppress host hematopoiesis prior to donor cell transplantation, the detection methods used to identify the progeny of donor-derived stem cells, and the endpoints and criteria for "successful" engraftment. (
  • HSC are rare cells that reside in adult bone marrow where hematopoiesis is continuously taking place. (
  • 1 There are 2 waves of hematopoiesis in vertebrates ( Figure 1 A). The primitive wave is derived from hemangioblasts that form in the posterior primitive streak and migrate onto the yolk sac (YS) from embryonic day 7 (E7.0) 2 , 3 where they give rise to primitive erythroid progenitors (EryP) in association with endothelial and vascular smooth muscle cells. (
  • This shows the contribution of ESAM to the ontogeny of definitive hematopoiesis and the functional involvement of ESAM-expressing endothelial cells. (
  • We'd like to continue our research so that our achievements will elucidate the mechanisms of hematopoiesis and lead to the identification of the cause of congenital disorders of the hematopoietic system, especially the cause of genetic anemia, and the development of treatment methods. (
  • Hematopoiesis is sustained by a renewable pool of stem cells that interacts with distinct, sequential and specific microenvironments during normal development and throughout adult life. (
  • Hematopoietic stem cell (HSC) migration throughout life is believed to be central to hematopoiesis under homeostasis. (
  • Eltrombopag (EP), a small-molecule thrombopoietin receptor (TPO-R) agonist and potent intracellular iron chelator, has shown remarkable efficacy in stimulating sustained multilineage hematopoiesis in patients with bone marrow failure syndromes, suggesting an effect at the most immature hematopoietic stem and multipotent progenitor level. (
  • Recently, aging has been linked with the development of age-related clonal hematopoiesis (ARCH), defined as the gradual clonal expansion of hematopoietic stem and progenitor cells (HSPC) carrying recurrent disruptive genetic variants in individuals without a diagnosis of hematologic malignancy. (
  • All the patients had gene-marked cells after engraftment, with no evidence of preferential integration near known oncogenes or clonal outgrowth. (
  • These data lay the groundwork for the exploration of EC therapies that can serve as adjuvant modalities to enhance HSC engraftment and accelerate hematopoietic recovery in the elderly population following myelosuppressive regimens. (
  • These experiments revealed that the combination of Viagra and Plerixafor outperforms Plerixafor alone, resulting in the long-term engraftment of functional, self-renewing, multipotent hematopoietic stem cells, suggesting that this approach may be suitable for hematopoietic stem cell transplantation in patients. (
  • This newly-issued patent expands the Company's significant intellectual property position covering ex vivo small molecule modulation of hematopoietic stem cells, which includes compositions and methods for enhanced lentiviral transduction and engraftment in the field of hematopoietic cell transplantation. (
  • This most recent patent, which expires in 2032, specifically covers compositions of hematopoietic stem and progenitor cells with increased CXCR4 gene expression and methods of increasing engraftment and reconstitution in patients by administering CXCR4-enhanced hematopoietic stem cells. (
  • 7 The use of blood stem cells is associated with faster recovery of neutrophils and platelets after transplantation (engraftment) than is the case with bone marrow stem cells. (
  • Transplantation assays performed in mice have proven invaluable for studying murine and human stem cell biology, facilitating an improved understanding of the immunophenotype, homing ability, engraftment properties, cytokine responsiveness and radiation sensitivity of repopulating cells. (
  • However, in contrast to the 100% donor hematopoietic engraftment typical of myeloablative transplantation, such nonmyeloablative transplants typically resulted in a state of mixed hematopoietic chimerism. (
  • The study, which involved 130 patients, also found that adding fludarabine to conditioning caused three-fold enhancement of hematopoietic cell engraftment. (
  • T cell depletion (TCD) of BM prevents GVHD, but is associated with significantly impaired engraftment ( 5 - 7 ). (
  • We were the first to identify a CD8 + /TCR − BM population that facilitates hematopoietic stem cell (HSC) engraftment across MHC barriers without causing GVHD ( 8 - 10 ). (
  • The expression of CD62L, HLA-DR and CD117 was modulated after culture, particularly with TPO + FL + KL, explaining differences between the adhesion and engraftment of primary and cultured candidate stem cells. (
  • Disadvantages of CB, compared to BM and MPB, include the low, and sometimes limiting, number of cells collected in single donor units which can be less than optimal for engraftment of many adults and higher weight children, and the relatively slower speed to engraftment of neutrophils and platelets. (
  • While limiting numbers of nucleated cells found in single units of CB can be compensated for by transplantation of more than 1 unit of CB, this use of multiple cord blood units may be associated with increased GVHD, and has not meaningfully reduced the time to neutrophil and platelet engraftment. (
  • Burt RK, Verda L, Kim D-A et al (2004) Embryonic stem cells as an alternate marrow donor source: engraftment without graft-versus-host disease. (
  • Highly purified in vivo transplantable mouse stem cells are maintained in AFT024 cultures at input levels, whereas other primitive progenitors are expanded. (
  • The hematopoietic tissue contains cells with long-term and short-term regeneration capacities and committed multipotent, oligopotent, and unipotent progenitors. (
  • G-CSF), some myelosuppressive drugs used in cancer treatment, and compounds that disrupt the interaction between hematopoietic and BM stromal cells can rapidly mobilize large numbers of stem and progenitors into the circulation. (
  • Later, myeloid progenitors generate neutrophils, and still later lymphoid progenitors (CLPs) seed the bone marrow and thymus where they provide B and T cells, respectively. (
  • Using appropriate StemSpan™ Expansion Supplements, SFEM may be used to expand CD34+ cells isolated from human cord blood, mobilized peripheral blood, or bone marrow samples, or to expand and differentiate lineage-committed progenitors to generate populations of erythroid, myeloid, or megakaryocyte progenitor cells. (
  • Ash1l deficiency also decreased expression of multiple Hox genes in hematopoietic progenitors. (
  • Overall health of the animals was good, and there were relatively minor changes in marrow hematopoietic progenitors. (
  • These cells are defined by their ability to self-renew as well as to differentiate into committed progenitors of the different myeloid and lymphoid compartments generating all of the blood cell lineages (1). (
  • Using Notch receptor blocking antibodies, we report that Notch2 blockade, but not Notch1 blockade, sensitizes hematopoietic stem cells and progenitors (HSPCs) to mobilization stimuli and leads to enhanced egress from marrow to the periphery. (
  • In addition, we found that Notch2-blocked or Notch2-deficient marrow HSPCs show an increased homing to the marrow, while mobilized Notch2-blocked, but not Notch2-deficient stem cells and progenitors, displayed a competitive repopulating advantage and enhanced hematopoietic reconstitution. (
  • Blazsek I, Chagraoui J, Péault B (2000) Ontogenic emergence of the hematon, a morphogenetic stromal unit that supports multipotential hematopoietic progenitors in mouse bone marrow. (
  • Zhang CC, Lodish HF (2005) Murine hematopoietic stem cells change their surface phenotype during ex vivo expansion. (
  • We have characterized a stem cell supportive stromal cell line, AFT024, that was derived from murine fetal liver. (
  • The classic OP9-DL1 culture system utilizes a coculture of HSPC with a murine bone marrow-derived stromal cell line (OP9) that ectopically expresses the Notch ligand, Delta-like 1 (Dll1). (
  • The phenotype of murine p-preDCs has now been characterized as a B220 + /CD11c dim /CD11b − cell population with a plasmacytoid morphology ( 24 , 28 ). (
  • Reprogramming committed murine blood cells to induced hematopoietic stem cells with defined factors. (
  • Batta K, Florkowska M, Kouskoff V, Lacaud G (2014) Direct reprogramming of murine fibroblasts to hematopoietic progenitor cells. (
  • Other conditions [13] treated with stem cell transplants include sickle-cell disease , myelodysplastic syndrome , neuroblastoma , lymphoma , Ewing's sarcoma , desmoplastic small round cell tumor , chronic granulomatous disease , Hodgkin's disease and Wiskott-Aldrich syndrome . (
  • In 2006 a total of 50,417 first hematopoietic stem cell transplants were reported as taking place worldwide, according to a global survey of 1327 centers in 71 countries conducted by the Worldwide Network for Blood and Marrow Transplantation. (
  • What are stem cell transplants used to treat? (
  • Stem cell transplants are approved to treat various cancers. (
  • Recent advances in hematopoietic stem cell biology have resulted in the use of HSC transplants in the treatment of cancers and other immune system disorders. (
  • Other conditions treated with stem cell transplants include sickle-cell disease , myelodysplastic syndrome , neuroblastoma , lymphoma , Ewing's Sarcoma , Desmoplastic small round cell tumor , Hodgkin's disease , and multiple myeloma . (
  • Allogeneic transplants are also performed using umbilical cord blood as the source of stem cells. (
  • Other patients who receive bone marrow transplants include pediatric cases where the patient has an inborn defect such as severe combined immunodeficiency or congenital neutropenia and was born with defective stem cells. (
  • Other conditions that bone marrow transplants are considered for include thalassemia major , sickle-cell disease , myelodysplastic syndrome , lymphoma , Hodgkin's disease , and multiple myeloma . (
  • Recipients of stem cell transplants may be severely immunocompromised for many months after transplantation, especially if they are still taking immunosuppressive drugs. (
  • Allogeneic transplantation represents 40% of all stem cell transplants performed annually in Canada and requires donor and recipient matching for major histocompatibility (HLA) antigens. (
  • It is interesting the investigators hypothesize that following the allogeneic bone marrow transplants that graft vs host disease (ie, donor cells killing host cells), in combination with ongoing ART, led to the potential eradication of HIV in these two patients. (
  • The importance of this effect was demonstrated by an increased rate of leukemia relapse in patients receiving transplants in which identical twin donors were used or T cell depletion of donor marrow was performed ( 5 ). (
  • This is clinically important because the reprogrammed cells could be transplanted to allow patients to fight infections after marrow transplants," Dr. Lis said. (
  • 1989 ), and subsequent CB transplants (Broxmeyer and Smith, 2009 ) were made possible by the biological laboratory studies that suggested CB as a potential source of transplantable hematopoietic stem (HSC) and progenitor (HPC) cells (Broxmeyer et al. (
  • In the case of transplants using HSC derived from other people, the conditioning therapy also helps reduce the risk of the recipient's body killing or rejecting the incoming donor stem cells (graft rejection). (
  • Another type of HSC source is cord blood cells that are used in umbilical cord blood transplants. (
  • Vor Biopharma is a cell therapy company that aims to transform the lives of cancer patients by pioneering engineered hematopoietic stem cell (eHSC) therapies to create next-generation, treatment-resistant transplants that unlock the potential of targeted therapies. (
  • To characterize the specific cell types that mediate stem cell expansion, we dissected this microenvironment into a panel of over 200 cloned stromal cell lines ( 7 , 8 ). (
  • The most potent stromal cell line, AFT024, maintains highly purified fetal and adult stem cell populations in vitro , for at least 4-7 weeks. (
  • To form organoids, MS5-DLL1 stromal cells are aggregated with HSPCs by centrifugation and cultured on a Millicell ® cell culture insert in defined serum-free media. (
  • The bone marrow (BM) microenvironment, consisting of the vascular endothelial cell (EC) and perivascular stromal niches, normally provides paracrine signals to support HSC maintenance and function. (
  • Depending on the agent, hematopoietic stem cells (HSC), hematopoietic progenitor, and marrow stromal cells can be infected. (
  • Non-HSC/HPC include mesenchymal stem/stromal cells (MSC), endothelial progenitor cells (EPC), and induced pluripotent stem cells (iPSC). (
  • Briefly, ESC are differentiated as embryoid bodies, which are then infected with retroviral HoxB4 and co-cultured with OP9 stromal cells and hematopoietic cytokines. (
  • As the embryo requires rapid oxygenation due to its high mitotic activity, these islands are the main source of red blood cell (RBC) production via fusing endothelial cells (ECs) with the developing embryonic circulation. (
  • A year later, Choi showed that blast cells derived from embryonic stem (ES) cells displayed common gene expression of both hematopoietic and endothelial precursors. (
  • Ablation of cDCs was associated with an expansion of bone marrow endothelial cells and increased vascular permeability. (
  • CXCR2 expression in sinusoidal endothelial cells and the expression of 2 CXCR2 ligands, CXCL1 and CXCL2, in the bone marrow were markedly increased following cDC ablation. (
  • Treatment of endothelial cells in vitro with CXCL1 induced increased vascular permeability and HSPC transmigration. (
  • Hemangioblasts, the multipotent precursor cells, differentiate into hematopoietic and vascular endothelial cells. (
  • The research team obtained vascular endothelial cells from mice and reprogrammed them to produce proteins that made them function like blood stem cells. (
  • As stated earlier, the current research team demonstrated that adult vascular endothelial cells could be programmed to become hematopoietic stem cells . (
  • Additional studies that may provide benefit are the assay for von Willebrand factor propeptide (VWFpp), a marker of endothelial cell damage, and the assay for thrombomodulin. (
  • 6 , 7 In mice, JAM-B expression is restricted to endothelial cells whereas JAM-C is expressed by various cell types including endothelial, 1 , 2 fibroblastic, 8 and smooth muscle cells. (
  • Chen MJ, Yokomizo T, Zeigler BM et al (2009) Runx1 is required for the endothelial to haematopoietic cell transition but not thereafter. (
  • In 2014, according to the World Marrow Donor Association (WMDA), stem cell products provided for unrelated transplantation worldwide had increased to 20,604 (4,149 bone marrow donations, 12,506 peripheral blood stem cell donations, and 3,949 cord blood units). (
  • The patient is then treated with high-dose chemotherapy with or without radiotherapy with the intention of eradicating the patient's malignant cell population at the cost of partial or complete bone marrow ablation (destruction of patient's bone marrow's ability to grow new blood cells). (
  • Bone marrow cells are collected during a surgical procedure that takes approximately an hour. (
  • After the marrow is collected, the cell suspension is passed through a series of sterile filters of decreasing size to remove fat, bone particles and cellular debris. (
  • Hematopoietic stem cells have an enormous clinical importance for bone marrow transplantation, hematopoietic gene therapy, solid organ transplantation, and somatic tissue regeneration. (
  • Allogeneic marrow stem-cell transplantation from human leukocyte antigen-identical siblings versus human leukocyte antigen-allelic-matched unrelated donors (10/10) in patients with standard-risk hematologic malignancy: a prospective study from the French society of bone marrow transplantation and cell therapy," Journal of Clinical Oncology , vol. 24, no. 36, pp. 5695-5702, 2006. (
  • Effect of HLA class II gene disparity on clinical outcome in unrelated donor hematopoietic cell transplantation for chronic myeloid leukemia: the US National Marrow Donor Program experience," Blood , vol. 98, no. 10, pp. 2922-2929, 2001. (
  • Bone marrow cells from Ly-5.1 mice were flushed from femurs and tibiae, pooled, and washed twice with phosphate-buffered saline containing 0.1% bovine serum albumin. (
  • As per survey by World Network for Blood and Marrow Transplantation (WBMN), around one million hematopoietic stem cell transplantation procedures were performed during 2006 to 2014, which indicates potential opportunities for market players. (
  • Understanding the role of the bone marrow (BM) microenvironment in supporting HSC function may prove to be beneficial in treating age-related functional hematopoietic decline. (
  • What are the current state-of-the-art treatment options, what are bone marrow stem cell transplantations, and what about immune therapy to treat hematological malignancies? (
  • Granulocytic sarcoma (GS) is a tumor consisting of malignant granulocytic precursor cells occurring at anatomical sites other than the bone marrow. (
  • Hematopoietic stem cells are found in the bone marrow of adults, especially in the pelvis, femur, and sternum. (
  • Another CFU, the colony-forming unit-spleen (CFU-S), was the basis of an in vivo clonal colony formation, which depends on the ability of infused bone marrow cells to give rise to clones of maturing hematopoietic cells in the spleens of irradiated mice after 8 to 12 days. (
  • This phenomenon is used in bone marrow transplantation, when a small number of Hematopoietic stem cells reconstitute the hematopoietic system. (
  • This process indicates that, subsequent to bone marrow transplantation, symmetrical cell divisions into two daughter Hematopoietic stem cells must occur. (
  • Stem cell self-renewal is thought to occur in the stem cell niche in the bone marrow, and it is reasonable to assume that key signals present in this niche will be important in self-renewal. (
  • In 1978, after observing that the prototypical colony-forming stem cells were less capable at replacing differentiated cells than bone marrow cells injected into irradiated animals, Schofield proposed that a specialized environment in the bone marrow allows these precursor cells to maintain their cellular reconstitution potential. (
  • 16. The method of claim 1, wherein the hematopoietic system reconstituting cells administered to the recipient are present in a source population of between 0.2 10 8 and 4.0 10 8 donor bone marrow cells/kg of recipient's body weight. (
  • Human hematopoietic stem and progenitor cells (HSPCs), derived from bone marrow, have become a primary vehicle for efforts to replace or regenerate cells destroyed by a variety of diseases. (
  • The combination of two clinically approved drugs--Viagra and Plerixafor--rapidly and efficiently mobilizes blood stem cells from the bone marrow into the bloodstream in mice, researchers report October 10th in the journal Stem Cell Reports. (
  • This procedure involves mobilizing hematopoietic stem cells from the bone marrow into the bloodstream and then collecting these cells for transplantation either back into the same person or into a recipient. (
  • Recent experiments in the Forsberg lab have shown that increasing vascular permeability helps mobilize hematopoietic stem cells from the bone marrow into the bloodstream. (
  • The researchers next harvested hematopoietic stem cells from the blood or bone marrow of donor mice treated with either Plerixafor alone or a combination of Viagra and Plerixafor and then transplanted these cells into recipient mice. (
  • Stem cell transplantation is a medical procedure in the fields of hematology and oncology , most often performed for people with diseases of the blood , bone marrow , or certain types of cancer . (
  • Stem cell transplantation was pioneered using bone-marrow-derived stem cells by a team at the Fred Hutchinson Cancer Research Center from the 1950s through the 1970s led by E. Donnall Thomas, whose work was later recognized with a Nobel Prize in Physiology and Medicine. (
  • Thomas' work showed that bone marrow cells infused intravenously could repopulate the bone marrow and produce new blood cells . (
  • With the availability of the stem cell growth factors GM-CSF and G-CSF, most hematopoietic stem cell transplantation procedures are now performed using stem cells collected from the peripheral blood, rather than from the bone marrow. (
  • The patient is then treated with high-dose chemotherapy with or without radiotherapy in the form of total body irradiation to eradicate the patient's malignant cell population at the cost of also eliminating the patient's bone marrow stem cells, then return of the patient's own stored stem cells to their body. (
  • Animation and slides providing graphic explanation of Bone Marrow Transplantation (BMT)/Stem Cell Transplantation that is done for leukemia and other blood-related disorders. (
  • Myelodysplastic syndromes are a group of bone marrow stem cell disorders marked by ineffective blood cell production and low counts in the peripheral blood. (
  • CXCR4 signaling has been proven to play a pivotal role in the homing of hematopoietic stem and progenitor cells to the bone marrow in vivo and is critical to realizing the curative potential of hematopoietic cell transplantation. (
  • Bone marrow transplantation was first attempted, albeit unsuccessfully, in 1939, when human bone marrow cells were injected intravenously to treat a patient with aplastic anemia. (
  • Although stem cells can be collected by direct aspiration from the bone marrow, with the patient under general or spinal anesthetic ( Fig. 1 ), they are now more commonly harvested from the peripheral blood. (
  • Fig. 1: Collection of stem cells by direct aspiration from bone marrow, with the donor under general anesthetic. (
  • Number of patients with donor chimerism - percentage of donor cells in the patient via the peripheral blood or bone marrow. (
  • Number of patients who had donor skin chimerism - donor cells in the patient's epidermis (a state in bone marrow transplantation in which bone marrow and host cells exist compatibly without signs of graft-versus-host rejection disease). (
  • HLA 10/10 matched allogeneic bone marrow cells will be infused into recipient (patient). (
  • Hi Piersgb, The 'gold standard' for proving that a cell derived from mouse bone marrow is indeed an HSC is still based on the same proof described above and used in mice many years ago. (
  • The study evaluates the effect of inactivation of the immune system with chemotherapy and immunotherapy and infusion of bone marrow stem cells in early onset type 1 diabetes mellitus. (
  • The discovery that the infusion of allogeneic hematopoietic stem cells can "rescue" patients from lethal marrow toxicity and give rise to a new donor-derived immunohematopoietic system resulted in successful treatments for patients with malignant or nonmalignant hematologic disease ( 2 , 3 ). (
  • Because even high doses of irradiation or chemotherapy cannot eradicate all malignant cells in all patients, ever more intensive conditioning regimens dominated efforts in clinical marrow transplantation until the late 1990s. (
  • In contrast to traditional allogeneic stem cell transplantation, in which the patient receives myeloablative conditioning (chemotherapy and/or irradiation), in NST, if donor cells are not infused or are rejected, the recipient's own bone marrow usually recovers spontaneously. (
  • Based on the experience of the pilot studies, the current protocol will mobilize stem cells with granulocyte-colony stimulating factor (G-CSF) and collect stem cells by apheresis, with subsequent bone marrow harvest performed only if needed to supplement the peripheral blood stem cells (PBSC). (
  • It involves the use of in vivo models of leukaemia development, which will be analysed by cutting edge multi-parameter flow cytometry, single-cell RNA sequencing, imaging of the bone marrow niche and computational/systems biology methods. (
  • In some cases, stem cells in your bone marrow may not be functioning well or need to be destroyed to help treat a disease. (
  • It may take about a month for the donor stem cells in the bone marrow to begin to function fully. (
  • This procedure is done if the stem cells in your bone marrow are not functioning or are deficient. (
  • It will rid the body of diseased cells and clear the bone marrow cavities for the new bone marrow. (
  • If the stem cells will be from the donor's bone marrow, an area of the donor's hip will be cleaned. (
  • The donor may also be required to take pills that cause more stem cells from the bone marrow to go into the blood. (
  • This is to avoid infection until the new stem cells in the bone marrow begin to produce infection-fighting cells. (
  • In this study, the expression of Flt3 protein and Flt3 mRNA by single cells within the hematopoietic stem cell (HSC) and HPC bone marrow compartments of C57/BL6 mice was investigated using flow cytometry and the quantitative reverse transcription polymerase chain reaction. (
  • Hematopoietic stem cell transplantation (bone marrow, cord blood, or peripheral blood stem cells) may cure aplastic anemia and prevent myelodysplastic syndrome or leukemia. (
  • demonstrated that, in addition to targeting the thrombopoietin receptor, eltrombopag also chelates iron and that this chelating action enables it to improve the function of bone marrow stem cells. (
  • These new drugs that inhibit PTP-sigma have the potential to accelerate human blood system recovery and human blood stem cell regeneration in patients who have received chemotherapy, radiation treatment or bone marrow transplantation. (
  • The concept that hematopoietic stem cell (HSC) numbers and behavior are regulated by physically discrete locations or niches within the bone marrow was first hypothesized in detail 30 yr ago ( Schofield, 1978 ). (
  • Early research specifically into cord blood transplantation was based on the hypothesis that the immune cells in cord blood may be less mature than those in adult bone marrow or peripheral blood. (
  • The CD34 + CD38 - immunophenotype defines a primitive subpopulation of progenitor cells in fetal liver and fetal or adult bone marrow (3-5). (
  • About 1% of bone marrow cells express CD34, and generally less than 1% of these cells are CD38-negative. (
  • The term haematopoietic stem cell (HSC) refers to cells made in the blood factory or bone marrow that have the potential to grow into almost any type of blood cell. (
  • The treatment that immediately precedes infusion of HSC is called conditioning therapy and is given to help kill tumour cells, "wipe out the memory" of the recipient's immune system, and create "space" within the bone marrow for the incoming stem cells to grow. (
  • The reinfusion of the patient's own stem cells acts to rescue the bone marrow from toxicity. (
  • While obesity can induce varied abnormalities in bone marrow components, it is unclear how diet might affect hematopoietic stem cell (HSC) self-renewal. (
  • In this study our hypothesis is that infusion of donor lymphocyte immune cells from the subject's bone marrow donor will activate the subject's immune system to attack their cancer. (
  • To generate a sufficient number of stem cells for life-long blood cell production, the hematopoietic stem cell population undergoes a period of extensive expansion in the mid-gestation fetal liver ( 6 ). (
  • From E11.5 to E15.5, there is a massive expansion of the FL, which is initially geared for production of definitive enucleated red blood cells to sustain rapid fetal growth ( Figure 1 A). From approximately E15.5, myeloid lineages are produced and hepatocytes begin to differentiate within the FL as it transforms from a hematopoietic organ into an adult liver. (
  • We suggest that the AFT024 cell line represents a component of an in vivo stem cell niche. (
  • These were tested for their ability to support primitive hematopoietic stem cells in ex vivo cultures. (
  • Plasticell also announced collaboration with Anthony Nolan, a research organization in blood cancer, to progress clinical development of Plasticell's ex vivo expanded cord blood-derived hematopoietic stem cell product in December 2017. (
  • ectopic expression of axin, which promotes β-catenin degradation, inhibited HSC growth in vitro and hematopoeitic reconstitution in vivo. (
  • Fate Therapeutics has pioneered the ex vivo use of small molecules, including prostaglandin pathway agonists, to modulate the safety and efficacy of hematopoietic cells prior to patient administration," said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. (
  • ProTmune is manufactured by modulating a donor-sourced, mobilized peripheral blood graft ex vivo with two small molecules (FT1050 and FT4145) to enhance the biological properties and therapeutic function of the graft's immune cells. (
  • Its adoptive cell therapy programs are based on the Company's novel ex vivo cell programming approach, which it applies to modulate the therapeutic function and direct the fate of immune cells. (
  • HSC population is then the ideal target for the correction of hematopoietic genetic diseases and also for the knockout of the responsible genes to in vitro and in vivo model those hematopoietic diseases. (
  • The duration and severity of these defects of host immunity vary due to multiple factors, such as graft manipulation and choice of graft type (donor and source), intensity of conditioning, in vivo T cell depletion, and choice, duration, and intensity of pharmacological graft-versus-host-disease (GvHD) prophylaxis and treatment. (
  • Flt3 ligand (FL), a key cytokine for p-preDC development ( 25 , 28 , 29 ), similarly regulates FCs in that FCs can be generated from FL-supplemented BM cell cultures, as well as expanded and mobilized in vivo in FL-treated mice. (
  • Expansion of human stem cells in ex vivo culture will likely have important applications in transplantation, stem cell marking, and gene therapy (2). (
  • Ex vivo culture is a crucial component of several clinical applications of stem/progenitor cells. (
  • A single stem cell has been proposed to be capable of more than 50 cell divisions or doublings in vivo and as such has the capacity to generate up to 10 15 cells, or sufficient cells for up to 60 years. (
  • Thus, means to enhance numbers and/or potency of collected cells and their engrafting capability through ex-vivo and/or in-vivo maneuvers would likely enhance the efficacy and applicability of CB transplantation. (
  • This system permits the selective elimination of dividing TK+ T-cells in vivo. (
  • When we silenced either VCAM-1 or M-CSFR in mice with myocardial infarction or in ApoE−/− mice with atherosclerosis, nanoparticle-enabled in vivo RNAi mitigated blood leukocytosis, limited inflammation in the ischemic heart, and reduced myeloid cell numbers in atherosclerotic plaques. (
  • Amabile G, Welner RS, Nombela-Arrieta C et al (2013) In vivo generation of transplantable human hematopoietic cells from induced pluripotent stem cells. (
  • Boisset J-C, van Cappellen W, Andrieu-Soler C et al (2010) In vivo imaging of haematopoietic cells emerging from the mouse aortic endothelium. (
  • HLA-DPB1 mismatch in HLA-A-B-DRB1 identical sibling donor stem cell transplantation and acute graft-versus-host disease," Transplantation , vol. 77, no. 7, pp. 1107-1110, 2004. (
  • Donor selection To avoid rejection of the transplanted stem cells or severe graft-versus-host disease , the donor should have the same human leukocyte antigens (HLA) as the recipient. (
  • ProTmune™ is an investigational programmed cellular immunotherapy undergoing clinical development for the prevention of acute graft-versus-host disease and cytomegalovirus infection in patients undergoing allogeneic hematopoietic cell transplantation. (
  • Acute Graft-Versus-Host Disease is a severe short-term complication created by infusion of donor cells into a foreign host. (
  • Accurate determination of immune system compatibility is vital to minimise graft failure and lethal attack from donor cells against recipient's normal tissues (graft-versus-host disease or GvHD). (
  • Varied in scope, and richly detailed with step-by-step instructions and notes on the pitfalls to be avoided, these readily reproducible protocols apply hematopoietic stem cells isolated from mouse and human tissues of both embryonic and adult origin. (
  • Both steps can be easily solved when the source of cells is extensive or can be expanded and manipulated in vitro extensively, such as immortalized cell lines or pluripotent stem cells (embryonic stem cells and induced pluripotent stem cells). (
  • We used high-throughput fluorescence-activated cell sorter to analyze 9 subsets of blood stem cells, progenitor cells, circulating red cells, and platelets in more than 1300 mouse embryos at embryonic day (E) 14.5. (
  • 1 One example of a pluripotent stem cell is the embryonic stem cell, found in the blastocyst stage of the developing embryo. (
  • Cerdan C, Rouleau A, Bhatia M (2004) VEGF-A165 augments erythropoietic development from human embryonic stem cells. (
  • Chew J-L, Loh Y-H, Zhang W et al (2005) Reciprocal transcriptional regulation of Pou5f1 and Sox2 via the Oct4/Sox2 complex in embryonic stem cells. (
  • This protocol details the derivation of transplantable hematopoietic stem cells from mouse embryonic stem cells (ESC) and their subsequent injection into lethally irradiated recipient mice. (
  • Kocabas F., Zheng J., Zhang C., Sadek H.A. (2014) Metabolic Characterization of Hematopoietic Stem Cells. (
  • We offer a broad range of tools and technologies to culture hematopoietic stem cells including Stemline ® optimized serum-free expansion media, growth factors, cytokines and a broad range or HSC related antibodies and characterization kits. (
  • Ongoing research on human hematopoietic cells is directed toward the identification, isolation and characterization of the primitive cell types that mediate rapid and/or sustained hematological recovery after cytoreductive therapy and transplantation. (
  • Bertrand JY, Giroux S, Golub R et al (2005) Characterization of purified intraembryonic hematopoietic stem cells as a tool to define their site of origin. (
  • Two related articles demonstrate a role for Wnt signaling, which is involved in various developmental processes, in promoting hematopoietic stem cell (HSC) proliferation and self-renewal. (
  • Here we demonstrate that chemical mutagenesis of mice combined with advances in hematopoietic stem cell reagents and genome resources can efficiently recover recessive mutations and identify genes essential for generation and proliferation of definitive hematopoietic stem cells and/or their progeny. (
  • Functions of various types of known HSC surface markers, especially the role of hematopoietic cells in ontogeny and proliferation, were not well understood. (
  • citation needed] Hematopoietic stem cells can be identified or isolated by the use of flow cytometry where the combination of several different cell surface markers (particularly CD34) are used to separate the rare Hematopoietic stem cells from the surrounding blood cells. (
  • Signalling pathways that control vertebrate haematopoietic stem cell specification. (
  • HPCs are used in the treatment of many malignant (e.g., leukemia, lymphoma) and non-malignant (e.g., sickle cell disease) diseases to replace or rebuild a patient's hematopoietic system. (
  • In addition, it is not suitable for the very ill, the elderly, or individuals with sickle cell disease. (
  • Myeloid and lymphoid lineages both are involved in dendritic cell formation. (
  • Expands cells from all appropriate hematopoietic lineages in a colony-forming unit. (
  • Their potential to make at least 8 different mature blood cell lineages is not realized until the FL bud is formed from the gut tube and a suitable microenvironment is established for HSC seeding. (
  • An RNA expression survey for known stem cell regulatory cytokines, both positive and negative, did not reveal significant differences among supportive and nonsupportive cell lines ( 8 ). (
  • Clinical HSC transplantation exploits this natural phenomenon through the enforced release of stem cells (referred to as "mobilization") by cytokines, such as G-CSF, and/or chemotherapy to facilitate their collection in blood by leukapheresis. (
  • When combined with the appropriate cytokines, SFEM has been used for the culture and expansion of hematopoietic cells isolated from other species, including mouse, non-human primate, and dog. (
  • The same cells can also respond to inflammatory cytokines ( 12 - 14 ). (
  • Infusion of young, HSC-supportive BM ECs enhanced hematopoietic recovery following myelosuppressive injury and restored endogenous HSC function in aged mice. (
  • Newswise - Researchers at University of California San Diego School of Medicine report that a single infusion of wildtype hematopoietic stem and progenitor cells (HSPCs) into a mouse model of Friedreich's ataxia (FA) measurably halted cellular damage caused by the degenerative disease. (
  • The actual transplantation of the cells is a simple process involving intravenous infusion of a liquid stem cell product through a large-bore central venous catheter over 1 to 2 hours. (
  • PURPOSE: To determine the safety and effectiveness of stem cell infusion in the treatment of RDEB. (
  • The purpose of the stem cell infusion is to evaluate whether this treatment will produce a normal immune system that will no longer attack the body. (
  • When young mice were exposed to myelosuppressive total body irradiation (TBI), infusion of young ECs promoted rapid hematopoietic recovery, whereas infusion of aged ECs promoted an aged phenotype including impaired HSC function and myeloid bias. (
  • Primary Objectives: This a pilot project to determine the feasibility of the preemptive CD8+ depleted T-cell donor lymphocyte infusion (DLI) in: - Reducing the incidence of graf. (
  • However, we recently reported that adult AML patients with GS had unique characteristics at the time of diagnosis, including younger age, higher white blood cell counts and higher frequency of French-British-American M4 and M5 morphology when compared with those without GS. (
  • A study by MacMillan et al reported that alternative donor hematopoietic cell transplantation had a high success rate in patients with Fanconi anemia who did not have a history of opportunistic infections or transfusions and who underwent conditioning with single fraction total body irradiation 300 cGy, cyclophosphamide, fludarabine, and antithymocyte globulin. (
  • however, if stem cells do transdifferentiate, then signals emanating from the microenvironment must play a crucial role. (
  • These studies and others supported the idea that bone cells create the HSC niche, and all the research that elucidated this specialized hematopoietic microenvironment stemmed from these landmark studies. (
  • The function of the aging BM microenvironment-in particular, that of ECs-in the hematopoietic aging process is not well understood. (
  • We examine and discuss recent findings that shed new light into the molecular connections that feed a complex network between stem cells and their microenvironment, implicating parallel mechanisms for non-hematopoietic stem cells. (
  • Such efforts require a deeper understanding of the cell biology of HSC and HPC, the microenvironment that nurtures these cells, and greater mechanistic insight into cell surface receptors and intracellular signaling pathways regulating HSC/HPC function. (
  • As well as using stem cells from a donor's blood, cells from umbilical cord blood can also be used. (
  • Umbilical cord stem cells are less developed than other stem cells, and this means that they can grow into different types of cells. (
  • Umbilical cord blood stem cells are frozen at birth, which is important because they do not suffer any environmental damage or aging. (
  • This question has significant clinical relevance because cord blood cells recently have emerged as an important source for stem cell transplantation. (
  • In this study, Cherqui's team transplanted wildtype HSPCs into an FA mouse model, reporting that the HSPCs engrafted and soon differentiated into macrophages in key regions of the mice's brain and spinal cord where they appeared to transfer wildtype FXN into deficient neurons and muscle cells. (
  • The blood stem cells will be derived from either related donor or unrelated umbilical cord blood or haploidentical donor. (
  • Past few months, i cultured cord blood hematopoietic stem cells. (
  • The rate of platelet and neutrophil recovery after CB transplantation tends to be slower than after BM or MPB transplantation, due in part to the smaller number of stem and progenitor cells in a typical single-cord graft. (
  • Cord Blood Stem Cell Transplantation-standards. (
  • Pluripotent cells can differentiate into all cell types except those that make up the extraembryonic membranes (placenta, umbilical cord, and amnion), which are derived from the trophoblast. (
  • Factors already shown to influence the outcome of cord blood transplantation include the numbers of cells in the cord blood, the size of the recipient, and the degree of human leukocyte antigen (HLA) match 4 between the donor and the recipient. (
  • Alternative sources of haematopoietic stem cells, such as HLA mismatched (haplo-identical) family members and cord blood, may be available. (
  • Cells were immunophenotyped by four-color fluorescence using antibodies against CD11c, CD31, CD49e, CD61, CD62L, CD117, and HLA-DR. Low-density cord blood contained 1.4 ± 0.9% CD34 + cells, 2.6 ± 2.1% of which were CD38-negative. (
  • Umbilical cord blood (CB) is a clinically useful source of hematopoietic stem (HSC) and progenitor (HPC) cells for treatment of a wide variety of malignant and non-malignant disorders. (
  • Cord blood was originally frozen and transplanted after defrost as totally unseparated cells, which included all nucleated cells and lysates from non-nucleated erythrocytes, without washing to ensure that all HSC/HPC collected were infused into the recipient (Broxmeyer et al. (
  • Unrelated hematopoietic stem cell donors as research subjects. (
  • If proven safe and effective in human clinical studies, 'clinicians could consider these findings when selecting treatment strategies for their patients and for volunteer donors of hematopoietic cells used in transplantation therapies. (
  • Twenty-four patients, 11 males and 13 females, median age 25 years (range 10-41 years) treated with haematopoietic stem cell transplantation from related (n = 9) or unrelated donors (n = 15) in 15 institutions worldwide were analysed for outcome and its associated factors. (
  • The two patients had received reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation from wild-type CCR5 donors. (
  • HLA testing will be performed on potential stem cell donors. (
  • Transplantation of BM or mobilized PB (MPB) cells from related or HLA-matched unrelated donors (so-called allogeneic transplantation) is a potentially life-saving and curative therapy for leukemia and other diseases of the blood and immune system. (
  • Using time-lapse microscopy, the researchers were able to observe the maturation of living hematopoietic stem cells with high precision while also quantifying certain proteins. (
  • Enforced expression of the ABCG2 cDNA resulted in a robust SP phenotype and a reduction in hematopoietic maturation. (
  • We reasoned that molecules responsible for the stem cell supportive phenotype would be preferentially expressed in AFT024 compared with nonsupporting lines derived from the same tissue source. (
  • Hematopoietic stem cells constitute 1:10,000 of cells in myeloid tissue. (
  • The researchers collected peripheral blood mononuclear cells by leukapheresis from both patients and rectal tissue from one patient to quantify HIV DNA and perform viral co-culture from CD4+ T lymphocytes. (
  • They also found no HIV p24 antigen in the CD4+ T cells, and there also was no HIV DNA detected in the rectal tissue. (
  • Hematopoietic stem cells (HSC) are well-characterized tissue-specific stem cells that exhibit remarkable self-renewal capacity and are responsible for the life-long maintenance of the hematopoietic system. (
  • Lead author, Dr. Chozhavendan Rathinam, is confident that "our findings may facilitate the expansion and manipulation of hematopoietic stem cells for tissue engineering and stem cell based therapies. (
  • It has been shown that crosstalk between the canonical NF-κB and Notch signaling pathways can influence tissue homeostasis in certain cell types, including hematopoietic progenitor cells ( 7 , 8 ). (
  • Our diet and microbiome have a big influence on our bodies, but how these directly influence tissue stem cell function remains poorly understood. (
  • Stem cell self-renewal is critical for tissue homeostasis, and its dysregulation can lead to organ failure or tumorigenesis. (
  • Tissue, cells or virus corresponding to Mouse Sca1/ Ly6A/E. (
  • HPCs are capable of forming mature blood cells, such as red blood cells (the cells that carry oxygen), platelets (the cells that help stop bleeding) and white blood cells (the cells that fight infections). (
  • Peripheral Blood Progenitor Cells (PBPCs) are another type of cell therapy product that contains HPCs. (
  • The cells are collected from the peripheral blood using an apheresis device, which acts like a centrifuge to remove whole blood from the donor and separate its components. (
  • Blood enters the machine and is processed so that the HPCs and other white blood cells are removed, while the remainder of the blood is returned to the donor through a second needle placed in the other arm. (
  • The unit then undergoes further processing (primarily to remove red blood cells) and cryopreservation (freezing) and is stored in a liquid nitrogen freezer for potential use at a later time. (
  • The basic cellular and molecular mechanisms underlying the production and function of blood cells. (
  • and hematopoietic stem cell transplantation and the development of techniques for establishing stable hematopoietic chimeras in order to treat heritable blood diseases. (
  • Rare subset of hematopoietic stem and progenitor cells control white blood cell production after a myocardial infarction. (
  • Comprehensive and state-of-the-art, Hematopoietic Stem Cell Protocols offers both novice and experienced investigators alike an invaluable compendium of highly practical techniques for studying a wide variety of stem cell topics, including blood formation, blood-based disease, and such blood cancers as leukemia. (
  • Peripheral blood stem cell allograft rejection mediated by CD4 + T lymphocytes recognizing a single mismatch at HLA-DP β 1*0901," Blood , vol. 98, no. 4, pp. 1122-1126, 2001. (
  • A T-cell epitope encoded by a subset of HLA-DPB1 alleles determines nonpermissive mismatches for hematologic stem cell transplantation," Blood , vol. 103, no. 4, pp. 1417-1424, 2004. (
  • Nonpermissive HLA-DPB1 disparity is a significant independent risk factor for mortality after unrelated hematopoietic stem cell transplantation," Blood , vol. 114, no. 7, pp. 1437-1444, 2009. (
  • Haematopoiesis is the process by which all mature blood cells are produced. (
  • It must balance enormous production needs (the average person produces more than 500 billion blood cells every day) with the need to regulate the number of each blood cell type in the circulation. (
  • Hematopoietic stem cells give rise to different types of blood cells, in lines called myeloid and lymphoid. (
  • Hematopoietic stem cells are essential to haematopoiesis, the formation of the cells within blood. (
  • Hematopoietic stem cells can replenish all blood cell types (i.e., are multipotent) and self-renew. (
  • One example is the generation of different types of blood cells from their precursors, the hematopoietic stem cells. (
  • As these cells are short-lived, there needs to be a steady turnover of new blood cells and the maintenance of an HSC pool. (
  • However, Ueno and Weissman provided the earliest contradiction to the hemangioblast theory when they saw that distinct ES cells mixed into a blastocyst resulted in more than 1 ES cell contributing to the majority of the blood islands found in the resultant embryo. (
  • 17. The method of claim 1, wherein the hematopoietic system reconstituting cells administered to the recipient are present in a source population of between 1.0 10 8 and 40 10 8 donor cytokine mobilized peripheral blood stem cells/kg of recipient's body weight. (
  • Hematopoietic stem cell transplantation, which replaces abnormal blood-forming stem cells with healthy cells, is a curative treatment for a variety of blood and immune disorders. (
  • Since the early 1990s and the availability of the stem cell growth factors GM-CSF and G-CSF , most hematopoeitic stem cell transplantation procedures have been performed with stem cells collected from the peripheral blood. (
  • Blood stem cell transplantation is accomplished by treating the donor with hematopoietic growth factors, which cause the stem cells to proliferate and circulate freely in the peripheral blood. (
  • The blood is then collected by venipuncture and subjected to leukapheresis to obtain the cells for transplantation. (
  • No HIV DNA was detected in any of the peripheral blood mononuclear cells from either patient, suggesting that the peripheral viral reservoir size decreased by 3 log 10 to 4 log 10 . (
  • That is, the cells are injected into a mouse that has received a dose of irradiation sufficient to kill its own blood-producing cells. (
  • If the mouse recovers and all types of blood cells reappear, the transplanted cells are deemed to have included stem cells. (
  • Mature blood cells have a finite life-span and must be continuously replaced throughout life. (
  • Is the Subject Area "Red blood cells" applicable to this article? (
  • Alveolar hemorrhage results from damage of the pulmonary microcirculation, loss of integrity in the alveolar-capillary basement membrane, and accumulation of red blood cells in the alveolar space ( 14 ). (
  • The cells will be recollected from peripheral blood by apheresis and refrigerated. (
  • Mild regimens are associated with no significant neutropenia (average neutrophil nadirs of ∼1,000/μl) and have minimal requirements for platelet or red blood cell transfusions. (
  • Stem cells are undeveloped cells that have the capacity to grow into mature blood cells, which normally circulate in the blood stream. (
  • Decoding the molecular cross-talk between blood stem cells and their niches, its role in the maintenance of homeostasis and the development of haematological malignancies. (
  • Stem cells produce red blood cells, white blood cells, and platelets. (
  • If the stem cells will be from the donor's blood, the doctor will stick a needle in the donor's large vein or veins in the arms. (
  • This machine will spin the blood so that the stem cells are concentrated. (
  • Normally, red and white blood cells temporarily decrease after the administration of the anti-tumor drug and recover later. (
  • Reprogrammed lab engineered HSC could be a game-changer in the treatment of several blood disorders such as leukemia, aplastic anemia and sickle cell anemia, according to ground breaking research conducted by scientists at Weill Cornell Medicine. (
  • This is exciting because it provides us with a path towards generating clinically useful quantities of normal stem cells for transplantation that may help us cure patients with genetic and acquired blood diseases," added co-senior author Dr. Joseph Scandura, an associate professor of medicine and scientific director of the Silver Myeloproliferative Neoplasms Center at Weill Cornell Medicine. (
  • They are capable of differentiating into all three blood cell types, namely red cells, white cells and platelets. (
  • We have discovered a receptor protein that is expressed by blood stem cells called PTP-sigma. (
  • This receptor inhibits blood stem cell expansion and recovery from injury. (
  • We developed a new class of drugs that specifically inhibit PTP-sigma on blood stem cells and cause the accelerated recovery of blood stem cells in mice following irradiation or chemotherapy treatment. (
  • This same treatment also causes human blood stem cells to regenerate faster following radiation exposure. (
  • For example, they divide and mature into cells of a specific type or limited spectrum of types (e.g., heart, muscle, blood, or brain cells). (
  • The complexity of this system is enormous, since as many as 10 10 erythrocytes and 10 8 -10 10 white blood cells are produced each hour each day during the lifetime of the individual. (
  • Dr Colin Phipps Diong, Parkway Cancer Centre's new consultant specialising in lymphoma and blood cancers, and haematopoietic stem cell transplantation, explains haematopoietic stem cell transplantation. (
  • The more common way is to collect them from the blood stream, or "peripheral blood stem cell harvesting. (
  • In this procedure, blood is drawn from one arm, which then goes through a machine that filters out stem cells and white blood cells. (
  • After conditioning therapy, stem cells are infused into the bloodstream (usually between 30 and 60 minutes), akin to a blood transfusion procedure. (
  • In this paper, we investigated how molecular pathways involved in blood stem cell maintenance were influenced by a high-fat diet. (
  • Bonzanni N, Garg A, Feenstra KA et al (2013) Hard-wired heterogeneity in blood stem cells revealed using a dynamic regulatory network model. (
  • Shizuru JA, Negrin RS, Weissman IL (2005) Hematopoietic stem and progenitor cells: clinical and preclinical regeneration of the hematolymphoid system. (
  • Immune Biology of Allogeneic Hematopoietic Stem Cell Transplantation: Models in Discovery and Translation, Second Edition once again provides clinical and scientific researchers with a deep understanding of the current research in this field and the implications for translational practice. (
  • Effect of matching of class I HLA alleles on clinical outcome after transplantation of hematopoietic stem cells from an unrelated donor," New England Journal of Medicine , vol. 339, no. 17, pp. 1177-1185, 1998. (
  • For example, we use very similar algorithms to analyse disease-associated patterns in the genome and identify biomarkers in clinical cell screens. (
  • Unique and cutting-edge, Genetic Modification of Hematopoietic Stem Cells: Methods and Protocols is an ideal, thorough resource to promote further research and the implementation of investigator-driven clinical studies using gene-modified hematopoietic cells. (
  • This book is a great help for the design of excellent research in basic hematology, oncology, genetics, and immunology, and also promote the implementation of investigator-driven clinical studies using gene-modified hematopoietic cells. (
  • The book should provide a road map for researchers, clinical investigators and regulators involved in modifying haematopoietic cells. (
  • Funding for this research came, in part, from the National Institutes of Health (R21-NS090066, RO1-DK090058) the Cystinosis Research Foundation the Sanford Stem Cell Clinical Center and the California Institute of Regenerative Medicine. (
  • Since the establishment of the autoimmune etiology of type 1 DM in the late 1970s, many clinical trials analyzing the effects of different types of immune interventions demonstrated that beta-cell preservation is an achievable target in different degrees. (
  • Potential approaches include the administration of granulocytes, since neutropenia is the single most important risk factor for invasive fungal infection, and preliminary clinical results suggest a benefit of adoptively transferred donor-derived antifungal T cells. (
  • In vitro data and animal studies demonstrate an antifungal effect of natural killer cells, but clinical data are lacking to date. (
  • Replication of this enormous cell amplification with hematopoietic growth factors in vitro would allow the generation of large numbers of cells that could be used for a variety of clinical applications (7). (
  • This information could provide the means to modulate these cells for greater clinical advantage. (
  • There is also the potential, as yet far from proven in a clinical sense for use of mature cells generated from HSC/HPC, and for non-HSC/HPC uses of CB. (
  • The goal of this clinical research study is to learn if giving donor lymphocyte cells and SGI-110 will help control AML and MDS. (
  • However, high costs associated with hematopoietic stem cell transplantation procedures are expected to hinder growth of the market. (
  • Stem cell antigen-1 helps maintain renal epithelial cell homeostasis and promotes recovery of renal function following ischemic acute kidney injury. (
  • Haematopoietic stem cell (HSC) homeostasis is tightly controlled by growth factors, signalling molecules and transcription factors. (
  • To identify new modulators of HSC formation and homeostasis, a panel of biologically active compounds was screened for effects on stem cell induction in the zebrafish aorta-gonad-mesonephros region. (
  • One of the key regulators is Notch, an extracellular signal with a critical role in hematopoietic homeostasis ( 1 ). (
  • Spred1 Safeguards Hematopoietic Homeostasis against Diet-Induced Systemic Stress. (
  • Home › About CIRM › Our Publications › Grantee publications › Spred1 Safeguards Hematopoietic Homeostasis against Diet-Induced Systemic Stress. (
  • Hematopoietic Stem-Cell Gene Therapy for Cerebral Adrenoleukodystrophy. (
  • Early results of this study suggest that Lenti-D gene therapy may be a safe and effective alternative to allogeneic stem-cell transplantation in boys with early-stage cerebral adrenoleukodystrophy. (
  • The book represents an outstanding work, which should not be missed in all biomedical research laboratories dealing with gene therapy of hematopoietic cells. (
  • Haematopoietic stem cells are attractive targets for gene therapy. (
  • The CLP then goes on to differentiate into more committed lymphoid precursor cells. (
  • In this reconstituted schematic, hematopoietic stem cells (HSC) transplanted in a mouse model of Friedreich's ataxia differentiate into microglial cells (red) and transfer mitochondrial protein (green) to neurons (blue), preventing neurodegeneration. (
  • EryP proliferate and differentiate synchronously to generate large nucleated red cells, which enter the circulation as the heart begins to beat at approximately E9.0. (
  • Like all stem cell populations, HSC reply upon asymmetric cell division to generate two different daughter cells: one future stem cell, and another cell that will further differentiate into a more specialized cell type. (
  • In contrast, pluripotent stem cells are less committed and retain the potential to differentiate into most other types of cells. (
  • The many approaches described employ not only molecular and cell biology techniques, but also animal model systems, and include hematopoietic stem cell expansion protocols and methods for the purification and genetic modification of stem cells. (
  • Today, cell biology is no longer limited to static states but also attempts to understand the dynamic development of cell populations. (
  • At this time, it is only possible to verify the decision retrospectively with cell surface markers," explains Dr. Carsten Marr, head of the Quantitative Single Cell Dynamics Research Group at the Helmholtz Zentrum München's Institute of Computational Biology (ICB). (
  • This book provides a comprehensive overview in our understanding of the biology and therapeutic potential of hematopoietic stem cells, and is aimed at those engaged in stem cell research: undergraduate and postgraduate science students, investigators and clinicians. (
  • Such phenotype-driven approaches will provide new knowledge of the genes, protein interactions, and regulatory networks that underpin stem cell biology. (
  • The mechanisms that regulate cell fate choices in all stem cell systems have cell-autonomous (stem cell intrinsic) and non-cell-autonomous (microenvironmental) components. (
  • Stem cells hold great promise for regenerative medicine and cell-based therapies ( 1 ). (
  • Increasing awareness about stem cell therapies among the population is also expected to propel growth of the hematopoietic stem cell transplantation market. (
  • Plasticell, which specializes in the development of stem cell technologies and cell-based therapies, announced entering into an agreement with Nan yang Technological University (NTU) in Singapore on March 2017, to advance its therapeutic stem cell pipeline. (
  • Also, GE Healthcare announced the introduction of Thaw CB1000, for thawing large volumes of cell therapies cryopreserved in cryo-bags majorly intended for use in research laboratory, in September 2017. (
  • But significant hurdles have caused hematopoietic cell therapies to be reserved mainly for patients who have malignant disease and have run out of other treatment options. (
  • Better harvesting protocols would significantly improve the success rate for current indications and open curative hematopoietic cell therapies to a wider spectrum of disorders,' Forsberg says. (
  • We believe this approach, which is backed by our extensive intellectual property, is broadly applicable to the development of hematopoietic cell therapies with novel biological properties and enhanced therapeutic functionality. (
  • HSPCs are also being investigated in cell-based therapies for non-hematopoietic disorders. (
  • CAMBRIDGE, Mass., July 08, 2021 - Vor Biopharma (Nasdaq: VOR or the Company), a cell therapy company pioneering engineered hematopoietic stem cell (eHSC) therapies combined with targeted therapies for the treatment of cancer, today announced the formation of a collaboration with Janssen Biotech, Inc. ("Janssen"), one of the Janssen Pharmaceutical Companies of Johnson & Johnson. (
  • By removing biologically redundant proteins from eHSCs, we design these cells and their progeny to be treatment-resistant to complementary targeted therapies, thereby enabling these therapies to selectively destroy cancer cells while sparing healthy cells. (
  • In vitro , various model systems have been employed to mimic thymic function supportive of T-cell development. (
  • StemSpan™ Serum-Free Expansion Medium (SFEM) has been developed and tested for the in vitro culture and expansion of human hematopoietic cells, when the appropriate growth factors and supplements are added. (
  • The Company's hematopoietic cell therapy pipeline is comprised of NK- and T-cell immuno-oncology programs, including off-the-shelf product candidates derived from engineered induced pluripotent cells, and immuno-regulatory programs, including product candidates to prevent life-threatening complications in patients undergoing hematopoietic cell transplantation and to promote immune tolerance in patients with autoimmune disease. (
  • The cell-surface marker, CD34, was first identified as a hematopoietic cell-surface antigen using the early human myeloblastic cell line KG-1a [ 6 , 7 ], which highly expresses CD34 and displays a strong potential for myeloid colony-forming cells [ 8 ]. (
  • The projects aims at understanding how myeloid leukaemia remodels the haematopoietic stem cell niche to favour leukaemia development. (
  • The fms-like tyrosine kinase 3 (Flt3) is a cell surface receptor that is expressed by various hematopoietic progenitor cells (HPC) and Flt3-activating mutations are commonly present in acute myeloid and lymphoid leukemias. (
  • Following myocardial infarction (MI), myeloid cells derived from the hematopoietic system drive a sharp increase in systemic leukocyte levels that correlates closely with mortality. (
  • The origin of these myeloid cells, and the response of hematopoietic stem and progenitor cells (HSPCs) to MI, however, is unclear. (
  • The present invention provides a method of transplanting hematopoietic system reconstituting cells from a donor into an allogeneic recipient comprising administering to the recipient, prior to the administration of the hematopoietic system reconstituting cells, an amount of mononuclear cells which are. (
  • Another patient, who had had evidence of disease progression on MRI, had withdrawn from the study to undergo allogeneic stem-cell transplantation and later died from transplantation-related complications. (
  • PTPsigma inhibitors promote hematopoietic stem cell regeneration. (
  • Home › About CIRM › Our Publications › Grantee publications › PTPsigma inhibitors promote hematopoietic stem cell regeneration. (
  • These studies demonstrate the therapeutic potential of selective, small-molecule PTPsigma inhibitors for human hematopoietic regeneration. (
  • We excluded patients with hepatomegaly, splenomegaly or disseminated infiltration of leukemia cells in the skin and the infiltration in the cerebrospinal fluid that did not associated with tumors of the central nervous system. (
  • Hematopoeitic stem cell transplantation remains a risky procedure and has always been reserved for patients with life threatening diseases. (
  • We conducted a retrospective analysis of all known patients suffering from mitochondrial neurogastrointestinal encephalomyopathy who underwent allogeneic haematopoietic stem cell transplantation between 2005 and 2011. (
  • This chapter will review and discuss how researchers are trying to solve them, all attempts that are ongoing and the potential application of the technology to the patients affected with hematopoietic genetic diseases. (
  • Patients with MNGIE will be transplanted with stem cells from an individual who is human leukocyte antigen (HLA) 10/10 matched. (
  • Patients will receive 2 X10 6 CD34 cells/kg weight. (
  • The patients will receive a nonmyeloablative conditioning regimen with cyclophosphamide and fludarabine, and after this, the cells will be injected intravenously. (
  • Although additional studies are required to further characterize the pathways and signals contributing to the EC-mediated HSC aging phenotype, the results suggest that cellular therapy with young ECs is a potentially promising strategy to revive aged HSC pools and accelerate hematopoietic recovery following myelosuppressive treatment regimens in elderly patients. (
  • A study by Wang et al suggested that in patients with Fanconi anemia, the 1-year overall survival rate following unrelated-donor hematopoietic stem cell transplantation is poor in those with clonal or complete copy gains in the q arm of chromosome 3 or with abnormalities in three or more chromosomes. (
  • Although the only therapy that can cure the pancytopenia is stem cell transplantation, androgens, to which approximately 50-75% of patients respond, are used for those in whom transplantation is not an option. (
  • Scientists at the Helmholtz Zentrum München and their partners at ETH Zurich and the Technical University of Munich (TUM) have now used it to determine the development of hematopoietic stem cells in advance. (
  • They also published a study in 'Nature' that already dealt with the development of hematopoietic stem cells. (
  • Lack of expression of lineage markers is used in combination with detection of several positive cell-surface markers to isolate hematopoietic stem cells. (
  • CD8 + /TCR − facilitating cells (FCs) are comprised of a heterogeneous population and share cell surface markers with T cells, but are distinct from them ( 11 ). (
  • Phenotypic analyses of several cell surface markers reveal that even this rare population is heterogeneous (6). (
  • Kocabas F, Zheng J, Thet S, Copeland NG, Jenkins NA, DeBerardinis RJ et al (2012) Meis1 regulates the metabolic phenotype and oxidant defense of hematopoietic stem cells. (
  • These results demonstrate that the BM vascular EC niche plays a key role in regulating hematopoietic system aging and that the HSC aging phenotype is characterized by impaired instructive functions of ECs. (
  • We conclude that culture of CD34 + cells with TPO + FL + KL results in a significant increase in the number of candidate stem cells with the CD34 + CD38 - phenotype. (

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