Hematopoietic Stem Cell Mobilization
Granulocyte Colony-Stimulating Factor
Hematopoietic Stem Cell Transplantation
Stem Cells
Antigens, CD34
Heterocyclic Compounds
Leukapheresis
Blood Component Removal
Transplantation, Autologous
Stem Cell Transplantation
Bone Marrow Cells
Hematopoiesis
Colony-Forming Units Assay
Peripheral Blood Stem Cell Transplantation
Compassionate Use Trials
Chemokine CXCL12
Bone Marrow
Stem Cell Niche
Cyclophosphamide
Mice, Inbred C57BL
Transplantation, Homologous
Cell Differentiation
Receptors, CXCR4
Cell Lineage
Blood Cell Count
Multiple Myeloma
Embryonic Stem Cells
Flow Cytometry
Cell Movement
Stem Cell Factor
Graft Survival
Etoposide
Lymphoma, Non-Hodgkin
Transplantation Conditioning
Cells, Cultured
Multipotent Stem Cells
Bone Marrow Transplantation
Graft vs Host Disease
Melphalan
Combined Modality Therapy
Treatment Outcome
Mesenchymal Stromal Cells
Fetal Blood
Antineoplastic Combined Chemotherapy Protocols
Cell Separation
Proto-Oncogene Proteins c-kit
Hematologic Neoplasms
Autografting with philadelphia chromosome-negative mobilized hematopoietic progenitor cells in chronic myelogenous leukemia. (1/889)
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)Modulation of VLA-4 and L-selectin expression on normal CD34+ cells during mobilization with G-CSF. (2/889)
We have evaluated the immunophenotype, functional activity and clonogenic potential of CD34+ cells from peripheral blood (PB) of normal donors before and after 4 and 6 days of G-CSF administration. The percentage and absolute number of CD34+ cells significantly increased at days 4 and 6 of G-CSF administration, compared to the steady-state level (P < 0.0001). Two-colour fluorescence analysis showed, at days 4 and 6, a lower proportion of CD34+/c-kit+ compared to the steady-state level (P < 0.0001), but a similar expression of CD13, CD33, CD38, HLA-DR and Thy-1 antigens on CD34+ cells. The expression of adhesion molecules on CD34+ cells revealed a significant reduction of CD11a (P = 0.009), CD18, CD49d and CD62L (P < 0.0001) at days 4 and 6, compared to the baseline level. Three-colour staining showed a reduction of the more immature compartment (34+/DR-/13-) and an increase of the more differentiated compartment (34+/DR+/13+). Downregulation of VLA-4 during mobilisation was seen almost exclusively on more committed cells (34+/13+); downregulation of CD62L, on the contrary, was observed on both early progenitors (34+/13-) and more committed cells (34+/13+). The expression of 34+/VLA-4+ decreased on both c-kit+ and c-kit- cells, while the expression of 34+/62L+ decreased on the c-kit+ cells only. In vivo administration of G-CSF reduced the adherence capacity of CD34+ cells to normal BM stroma; in vitro incubation with SCF or IL-3 enhanced the expression of CD49d on CD34+ cells, while GM-CSF reduced the expression of CD62L. SCF was the only cytokine able to induce a significant increase of CD34+ cell adherence to preformed stroma. Pre-incubation with the blocking beta2 integrin monoclonal antibody caused a reduction of CD34+ cell adherence. In conclusion, the decrease of CD49d expression on mobilized CD34+ cells correlates with a poor adhesion to BM stroma; CD34+ cells incubated in vitro with SCF showed, conversely, a higher expression of CD49d and a greater adherence capacity on normal preformed stroma. (+info)The minimum CD34 threshold depends on prior chemotherapy in autologous peripheral blood stem cell recipients. (3/889)
We analysed 57 patients with non-myeloid malignancies who received a non-purged autologous PBSCT. All had similar mobilisation and conditioning regimens. A high prior chemotherapy score and the number of chemotherapy lines used (P = 0.015 and P = 0.01, respectively) were adverse predictors of CD34 cell yields. Lower CD34 values (P = 0.002) were seen in patients treated with potent stem cell toxins (BCNU, melphalan, CCNU and mustine), designated toxicity factor 4 agents (TF4). All patients infused with grafts containing CD34 cell doses between 1.0 and 2.0 x 10(6)/kg (range 1.25-1.90) engrafted by day 51. The only variable associated with slow platelet recovery was exposure to TF4 (P = 0.007). The majority of patients with CD34 >1.0 x 10(6)/kg achieved rapid and sustained engraftment and the only predictive factor of delayed recovery is prior exposure to stem cell toxins. Potential PBSCT candidates should if possible avoid first line and salvage chemotherapy containing TF4 drugs. We therefore advocate a minimum CD34 threshold of >1.0 x 10(6)/kg in patients without extensive prior chemoradiotherapy, and > or = 2.0 x 10(6)/kg in all other patients. (+info)Effects of short-term administration of G-CSF (filgrastim) on bone marrow progenitor cells: analysis of serial marrow samples from normal donors. (4/889)
To determine the effect of G-CSF administration on both the total number of CD34+ cells and the primitive CD34+ subsets in bone marrow (BM), we have analyzed BM samples serially obtained from 10 normal donors in steady-state and during G-CSF treatment. Filgrastim was administered subcutaneously at a dosage of 10 microg/kg/day (n = 7) or 10 microg/kg/12 h (n = 3) for 4 consecutive days. Peripheral blood sampling and BM aspirates were performed on day 1 (just before G-CSF administration), day 3 (after 2 days of G-CSF), and day 5 (after 4 days of G-CSF). During G-CSF administration, a significant increase in the total number of BM nucleated cells was observed. The percentage (range) of CD34+ cells decreased in BM from a median of 0.88 (0.47-1.44) on day 1 to 0.57 (0.32-1.87), and to 0.42 (0.16-0.87) on days 3 and 5, respectively. We observed a slight increase in the total number of BM CD34+ cells on day 3 (0.66 x 10(9)/l (0.13-0.77)), and a decrease on day 5 (0.23 x 10(9)/l (0.06-1.23)) as compared with steady-state (0.40 x 10(9)/l (0.06-1.68)). The proportion of primitive BM hematopoietic progenitor cells (CD34+CD38-, CD34+HLA-DR-, CD34+CD117-) decreased during G-CSF administration. In parallel, a significant increase in the total number of CD34+ cells in peripheral blood was observed, achieving the maximum value on day 5. These results suggest that in normal subjects the administration of G-CSF for 5 days may reduce the number of progenitor cells in BM, particularly the most primitive ones. (+info)Immunoregulatory cytokines in bone marrow and peripheral blood stem cell products. (5/889)
In these studies, we compared the phenotype, function, and expression of type 1, type 2, and monocyte-associated cytokine mRNA transcripts in autologous bone marrow (BM) and growth factor-mobilized peripheral blood stem cell (PSC) products. These studies demonstrate that lymphocytes and monocytes in stem cell products are abnormally activated, expressing significantly higher levels of interleukin (IL)-2, 4 and 10, interferon gamma (IFN-gamma), and tumor necrosis factor alpha (TNF-alpha), but not IL-8, as compared to normal peripheral blood mononuclear cells (PBMC). In addition, the levels of IL-2, IL-10 and TNF-alpha are significantly higher in mobilized PSC as compared to BM products. The high cytokine levels are unexpected as T cell function in stem cell products is depressed. PSC products have high levels of T cell inhibitory activity, which directly correlates with IL-10 expression, both of which are mechanisms that might be involved in the immune dysfunction within stem cell products used for autologous stem cell transplantation. These data demonstrate that: (1) immune cells in autologous BM and PSC products are activated with the expression of high levels of type 1 and type 2 cytokines as well as monokines; (2) PSC products contain a high frequency of monocytes which mediate T cell inhibitory activity; and (3) despite the high levels of cytokine expression, T cell function in stem cell products is depressed. The significance of these immune abnormalities within stem cell products for myeloid and lymphoid recovery following autologous stem cell transplantation remains to be determined. (+info)Comparison of monocyte-dependent T cell inhibitory activity in GM-CSF vs G-CSF mobilized PSC products. (6/889)
This study compares the immune properties of peripheral blood stem cell (PSC) products mobilized with different hematopoietic growth factors (HGFs) as well as apheresis products and peripheral blood leukocytes (PBL) from normal individuals. We found that monocytes in mobilized PSC products appear to inhibit T cell function independent of whether granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) was used for mobilization. In addition, the GF used to mobilize the stem cell product may be less important to the CD4:CD8 ratio than the extent of prior chemotherapy, as we found an inverse correlation between chemotherapy and the CD4:CD8 ratio. In other observations, all apheresis products, whether mobilized or unmobilized, contained significantly more monocytes compared to normal PBL. The mononuclear cells (MNC) from G-CSF or GM-CSF mobilized PSC products had a similar T cell phytohemagglutinin (PHA) mitogenic response that was significantly lower (P = 0.001 and P = 0.005, respectively) than non-mobilized apheresis products. We also examined the T cell inhibitor (TI) activity of the MNC from the PSC products for allogeneic lymphocyte proliferation and found that PSC products significantly reduced the proliferation of allogeneic PBL to PHA. A significant correlation (P = 0.001, r = 0.517) between the frequency of monocytes and TI activity also was observed. (+info)Early harvest and late transplantation as an effective therapeutic strategy in multiple myeloma. (7/889)
Transplantation after high-dose chemotherapy prolongs survival in patients with multiple myeloma compared with standard therapy. It is unclear whether the optimal timing of transplantation is immediately after induction chemotherapy or whether stem cells may be cryopreserved for transplantation at subsequent progression or relapse. In this study, stem cells were collected within 6 months of diagnosis, followed by transplantation only at progression of myeloma. One hundred and eighteen patients with multiple myeloma had stem cells collected and cryopreserved. Eleven had transplants early in the disease after they demonstrated failure to respond to primary therapy. The remaining 107 were eligible for transplants when there was evidence of progressive disease. Of the 118 patients, 67 had transplants, nine died of progressive disease before transplantation, and 42 remain alive in plateau phase. The median survival of the group is 58.5 months; 67 are alive. Serum beta2-microglobulin, bone marrow labeling index (S phase), and hemoglobin level predicted overall survival (P < 0.006, P < 0.001, and P < 0.01, respectively). We conclude that early cryopreservation of blood stem cells followed by transplantation at progression is a feasible approach to therapy in patients with myeloma. The underlying biology of the disease has a greater impact on survival than the timing of transplantation. A prospective randomized trial is required to answer definitively the question of the optimal timing of blood cell transplantation. (+info)Autologous transplantation of chemotherapy-purged PBSC collections from high-risk leukemia patients: a pilot study. (8/889)
We have recently demonstrated that the combination of the alkylating agent nitrogen mustard (NM) and etoposide (VP-16) is capable of eliminating, ex vivo, leukemic cells contaminating PBSC collections and this is associated with a significant recovery of primitive and committed hematopoietic progenitor cells. Based on these data a pilot study on autologous transplantation of NM/VP-16 purged PBSC for high-risk leukemic patients was recently initiated. Twelve patients (seven females and five males) with a median age of 46 years (range 18-57) have been treated. Two patients had acute myeloblastic leukemia (AML) resistant to conventional induction treatment, four patients had secondary AML in I complete remission (CR), one patient was in II CR after failing a previous autologous BM transplantation, while two additional AML individuals were in I CR achieved after three or more cycles of induction treatment. Two patients with high-risk acute lymphoblastic leukemia (ALL) in I CR and one patient with mantle cell lymphoma and leukemic dissemination were also included. Eight patients showed karyotypic abnormalities associated with a poor clinical outcome. The mobilizing regimens included cytosine arabinoside and mitoxantrone with (n = 6) or without fludarabine (n = 3) followed by subcutaneous administration of G-CSF (5 microg/kg/day until the completion of PBSC collection) and G-CSF alone (n = 3) (15 microg/kg/day). A median of two aphereses (range 1-3) allowed the collection of 7.2 x 10(8) TNC/kg (range 3.4-11.5), 5 x 10(6) CD34+ cells/kg (range 2.1-15.3) and 9.2 x 10(4) CFU-GM/kg (0.3-236). PBSC were treated with a constant dose of 20 microg of VP-16/ml and a median individual-adjusted dose (survival < or = 5% of steady-state BM CFU-GM) of NM of 0.7 microg/ml (range 0.25-1.25). Eleven patients were reinfused after busulfan (16 mg/kg) and Cy (120 mg/kg) conditioning with a median residual dose of 0.3 x 10(4) CFU-GM/kg (0-11.5). The median time to neutrophil engraftment (>0.5 x 10(9)/l) for evaluable patients was 25 days (range 12-59); the median time to platelet transfusion independence (>20 and >50 x 10(9)/l) was 40 days (18-95) and 69 days (29-235), respectively. Hospital discharge occurred at a median of 25 days (18-58) after stem cell reinfusion. Four individuals are alive in CR (n = 3) or with residual nodal disease (n = 1 lymphoma patient) with a follow-up of 32, 26, 3 and 14 months, respectively. Seven patients died due to disease progression or relapse (n = 5) or extrahematological transplant toxicity (n = 2). Our data suggest that pharmacological purging of leukapheresis collections of leukemic patients at high-risk of relapse is feasible and ex vivo treated cells reconstitute autologous hematopoiesis. (+info)Hematopoietic Stem Cell Mobilization is the process of mobilizing hematopoietic stem cells (HSCs) from the bone marrow into the peripheral blood. HSCs are immature cells that have the ability to differentiate into all types of blood cells, including red and white blood cells and platelets.
Mobilization is often achieved through the use of medications such as granulocyte-colony stimulating factor (G-CSF) or plerixafor, which stimulate the release of HSCs from the bone marrow into the peripheral blood. This allows for the collection of HSCs from the peripheral blood through a procedure called apheresis.
Mobilized HSCs can be used in stem cell transplantation procedures to reconstitute a patient's hematopoietic system after high-dose chemotherapy or radiation therapy. It is an important process in the field of regenerative medicine and has been used to treat various diseases such as leukemia, lymphoma, and sickle cell disease.
Granulocyte Colony-Stimulating Factor (G-CSF) is a type of growth factor that specifically stimulates the production and survival of granulocytes, a type of white blood cell crucial for fighting off infections. G-CSF works by promoting the proliferation and differentiation of hematopoietic stem cells into mature granulocytes, primarily neutrophils, in the bone marrow.
Recombinant forms of G-CSF are used clinically as a medication to boost white blood cell production in patients undergoing chemotherapy or radiation therapy for cancer, those with congenital neutropenia, and those who have had a bone marrow transplant. By increasing the number of circulating neutrophils, G-CSF helps reduce the risk of severe infections during periods of intense immune suppression.
Examples of recombinant G-CSF medications include filgrastim (Neupogen), pegfilgrastim (Neulasta), and lipegfilgrastim (Lonquex).
Hematopoietic stem cells (HSCs) are immature, self-renewing cells that give rise to all the mature blood and immune cells in the body. They are capable of both producing more hematopoietic stem cells (self-renewal) and differentiating into early progenitor cells that eventually develop into red blood cells, white blood cells, and platelets. HSCs are found in the bone marrow, umbilical cord blood, and peripheral blood. They have the ability to repair damaged tissues and offer significant therapeutic potential for treating various diseases, including hematological disorders, genetic diseases, and cancer.
Hematopoietic Stem Cell Transplantation (HSCT) is a medical procedure where hematopoietic stem cells (immature cells that give rise to all blood cell types) are transplanted into a patient. This procedure is often used to treat various malignant and non-malignant disorders affecting the hematopoietic system, such as leukemias, lymphomas, multiple myeloma, aplastic anemia, inherited immune deficiency diseases, and certain genetic metabolic disorders.
The transplantation can be autologous (using the patient's own stem cells), allogeneic (using stem cells from a genetically matched donor, usually a sibling or unrelated volunteer), or syngeneic (using stem cells from an identical twin).
The process involves collecting hematopoietic stem cells, most commonly from the peripheral blood or bone marrow. The collected cells are then infused into the patient after the recipient's own hematopoietic system has been ablated (or destroyed) using high-dose chemotherapy and/or radiation therapy. This allows the donor's stem cells to engraft, reconstitute, and restore the patient's hematopoietic system.
HSCT is a complex and potentially risky procedure with various complications, including graft-versus-host disease, infections, and organ damage. However, it offers the potential for cure or long-term remission in many patients with otherwise fatal diseases.
According to the National Institutes of Health (NIH), stem cells are "initial cells" or "precursor cells" that have the ability to differentiate into many different cell types in the body. They can also divide without limit to replenish other cells for as long as the person or animal is still alive.
There are two main types of stem cells: embryonic stem cells, which come from human embryos, and adult stem cells, which are found in various tissues throughout the body. Embryonic stem cells have the ability to differentiate into all cell types in the body, while adult stem cells have more limited differentiation potential.
Stem cells play an essential role in the development and repair of various tissues and organs in the body. They are currently being studied for their potential use in the treatment of a wide range of diseases and conditions, including cancer, diabetes, heart disease, and neurological disorders. However, more research is needed to fully understand the properties and capabilities of these cells before they can be used safely and effectively in clinical settings.
CD34 is a type of antigen that is found on the surface of certain cells in the human body. Specifically, CD34 antigens are present on hematopoietic stem cells, which are immature cells that can develop into different types of blood cells. These stem cells are found in the bone marrow and are responsible for producing red blood cells, white blood cells, and platelets.
CD34 antigens are a type of cell surface marker that is used in medical research and clinical settings to identify and isolate hematopoietic stem cells. They are also used in the development of stem cell therapies and transplantation procedures. CD34 antigens can be detected using various laboratory techniques, such as flow cytometry or immunohistochemistry.
It's important to note that while CD34 is a useful marker for identifying hematopoietic stem cells, it is not exclusive to these cells and can also be found on other cell types, such as endothelial cells that line blood vessels. Therefore, additional markers are often used in combination with CD34 to more specifically identify and isolate hematopoietic stem cells.
Heterocyclic compounds are organic compounds that contain at least one atom within the ring structure, other than carbon, such as nitrogen, oxygen, sulfur or phosphorus. These compounds make up a large class of naturally occurring and synthetic materials, including many drugs, pigments, vitamins, and antibiotics. The presence of the heteroatom in the ring can have significant effects on the physical and chemical properties of the compound, such as its reactivity, stability, and bonding characteristics. Examples of heterocyclic compounds include pyridine, pyrimidine, and furan.
Leukapheresis is a medical procedure that involves the separation and removal of white blood cells (leukocytes) from the blood. It is performed using a specialized machine called an apheresis instrument, which removes the desired component (in this case, leukocytes) and returns the remaining components (red blood cells, platelets, and plasma) back to the donor or patient. This procedure is often used in the treatment of certain blood disorders, such as leukemia and lymphoma, where high white blood cell counts can cause complications. It may also be used to collect stem cells for transplantation purposes. Leukapheresis is generally a safe procedure with minimal side effects, although it may cause temporary discomfort or bruising at the site of needle insertion.
Blood component removal, also known as blood component therapy or apheresis, is a medical procedure that involves separating and removing specific components of the blood, such as red blood cells, white blood cells, platelets, or plasma, while returning the remaining components back to the donor or patient. This process can be used for therapeutic purposes, such as in the treatment of certain diseases and conditions, or for donation, such as in the collection of blood products for transfusion. The specific method and equipment used to perform blood component removal may vary depending on the intended application and the particular component being removed.
Autologous transplantation is a medical procedure where cells, tissues, or organs are removed from a person, stored and then returned back to the same individual at a later time. This is different from allogeneic transplantation where the tissue or organ is obtained from another donor. The term "autologous" is derived from the Greek words "auto" meaning self and "logos" meaning study.
In autologous transplantation, the patient's own cells or tissues are used to replace or repair damaged or diseased ones. This reduces the risk of rejection and eliminates the need for immunosuppressive drugs, which are required in allogeneic transplants to prevent the body from attacking the foreign tissue.
Examples of autologous transplantation include:
* Autologous bone marrow or stem cell transplantation, where stem cells are removed from the patient's blood or bone marrow, stored and then reinfused back into the same individual after high-dose chemotherapy or radiation therapy to treat cancer.
* Autologous skin grafting, where a piece of skin is taken from one part of the body and transplanted to another area on the same person.
* Autologous chondrocyte implantation, where cartilage cells are harvested from the patient's own knee, cultured in a laboratory and then implanted back into the knee to repair damaged cartilage.
Stem cell transplantation is a medical procedure where stem cells, which are immature and unspecialized cells with the ability to differentiate into various specialized cell types, are introduced into a patient. The main purpose of this procedure is to restore the function of damaged or destroyed tissues or organs, particularly in conditions that affect the blood and immune systems, such as leukemia, lymphoma, aplastic anemia, and inherited metabolic disorders.
There are two primary types of stem cell transplantation: autologous and allogeneic. In autologous transplantation, the patient's own stem cells are collected, stored, and then reinfused back into their body after high-dose chemotherapy or radiation therapy to destroy the diseased cells. In allogeneic transplantation, stem cells are obtained from a donor (related or unrelated) whose human leukocyte antigen (HLA) type closely matches that of the recipient.
The process involves several steps: first, the patient undergoes conditioning therapy to suppress their immune system and make space for the new stem cells. Then, the harvested stem cells are infused into the patient's bloodstream, where they migrate to the bone marrow and begin to differentiate and produce new blood cells. This procedure requires close monitoring and supportive care to manage potential complications such as infections, graft-versus-host disease, and organ damage.
Bone marrow cells are the types of cells found within the bone marrow, which is the spongy tissue inside certain bones in the body. The main function of bone marrow is to produce blood cells. There are two types of bone marrow: red and yellow. Red bone marrow is where most blood cell production takes place, while yellow bone marrow serves as a fat storage site.
The three main types of bone marrow cells are:
1. Hematopoietic stem cells (HSCs): These are immature cells that can differentiate into any type of blood cell, including red blood cells, white blood cells, and platelets. They have the ability to self-renew, meaning they can divide and create more hematopoietic stem cells.
2. Red blood cell progenitors: These are immature cells that will develop into mature red blood cells, also known as erythrocytes. Red blood cells carry oxygen from the lungs to the body's tissues and carbon dioxide back to the lungs.
3. Myeloid and lymphoid white blood cell progenitors: These are immature cells that will develop into various types of white blood cells, which play a crucial role in the body's immune system by fighting infections and diseases. Myeloid progenitors give rise to granulocytes (neutrophils, eosinophils, and basophils), monocytes, and megakaryocytes (which eventually become platelets). Lymphoid progenitors differentiate into B cells, T cells, and natural killer (NK) cells.
Bone marrow cells are essential for maintaining a healthy blood cell count and immune system function. Abnormalities in bone marrow cells can lead to various medical conditions, such as anemia, leukopenia, leukocytosis, thrombocytopenia, or thrombocytosis, depending on the specific type of blood cell affected. Additionally, bone marrow cells are often used in transplantation procedures to treat patients with certain types of cancer, such as leukemia and lymphoma, or other hematologic disorders.
Hematopoiesis is the process of forming and developing blood cells. It occurs in the bone marrow and includes the production of red blood cells (erythropoiesis), white blood cells (leukopoiesis), and platelets (thrombopoiesis). This process is regulated by various growth factors, hormones, and cytokines. Hematopoiesis begins early in fetal development and continues throughout a person's life. Disorders of hematopoiesis can result in conditions such as anemia, leukopenia, leukocytosis, thrombocytopenia, or thrombocytosis.
A Colony-Forming Units (CFU) assay is a type of laboratory test used to measure the number of viable, or living, cells in a sample. It is commonly used to enumerate bacteria, yeast, and other microorganisms. The test involves placing a known volume of the sample onto a nutrient-agar plate, which provides a solid growth surface for the cells. The plate is then incubated under conditions that allow the cells to grow and form colonies. Each colony that forms on the plate represents a single viable cell from the original sample. By counting the number of colonies and multiplying by the known volume of the sample, the total number of viable cells in the sample can be calculated. This information is useful in a variety of applications, including monitoring microbial populations, assessing the effectiveness of disinfection procedures, and studying microbial growth and survival.
Peripheral Blood Stem Cell Transplantation (PBSCT) is a medical procedure that involves the transplantation of stem cells, which are immature cells found in the bone marrow that can develop into different types of blood cells. In PBSCT, these stem cells are collected from the peripheral blood instead of directly from the bone marrow.
The process begins with mobilization, where a growth factor medication is given to the donor to stimulate the release of stem cells from the bone marrow into the peripheral blood. After several days, the donor's blood is then removed through a procedure called apheresis, where the stem cells are separated and collected while the remaining blood components are returned to the donor.
The collected stem cells are then infused into the recipient's bloodstream, where they migrate to the bone marrow and begin to repopulate, leading to the production of new blood cells. This procedure is often used as a treatment for various malignant and non-malignant disorders, such as leukemia, lymphoma, multiple myeloma, and aplastic anemia.
PBSCT offers several advantages over traditional bone marrow transplantation, including faster engraftment, lower risk of graft failure, and reduced procedure-related morbidity. However, it also has its own set of challenges, such as the potential for increased incidence of chronic graft-versus-host disease (GVHD) and the need for more stringent HLA matching between donor and recipient.
Compassionate use trials, also known as expanded access or compassionate use programs, refer to the use of an experimental medical treatment outside of a clinical trial, typically for patients who have a serious or life-threatening condition and have exhausted all other available treatment options. These programs are designed to provide access to investigational therapies that have not yet been approved by regulatory authorities but have shown promising results in earlier stages of clinical development.
In compassionate use trials, patients receive the experimental therapy under a specific treatment protocol that outlines the dosage, administration, and monitoring requirements. The primary goal of these trials is to provide potential therapeutic benefits to patients who have no other alternatives, while also gathering additional safety and efficacy data on the investigational treatment.
Regulatory agencies such as the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have guidelines and procedures in place for compassionate use trials to ensure that patients receive appropriate care, and that the safety and well-being of participants are protected throughout the process.
Chemokine (C-X-C motif) ligand 12 (CXCL12), also known as stromal cell-derived factor 1 (SDF-1), is a small signaling protein belonging to the chemokine family. Chemokines are a group of cytokines, or signaling molecules, that play important roles in immune responses and inflammation by recruiting and activating various immune cells.
CXCL12 is produced by several types of cells, including stromal cells, endothelial cells, and certain immune cells. It exerts its effects by binding to a specific receptor called C-X-C chemokine receptor type 4 (CXCR4), which is found on the surface of various cell types, including immune cells, stem cells, and some cancer cells.
The CXCL12-CXCR4 axis plays crucial roles in various physiological processes, such as embryonic development, tissue homeostasis, hematopoiesis (the formation of blood cells), and neurogenesis (the formation of neurons). Additionally, this signaling pathway has been implicated in several pathological conditions, including cancer metastasis, inflammatory diseases, and HIV infection.
In summary, Chemokine CXCL12 is a small signaling protein that binds to the CXCR4 receptor and plays essential roles in various physiological processes and pathological conditions.
Bone marrow is the spongy tissue found inside certain bones in the body, such as the hips, thighs, and vertebrae. It is responsible for producing blood-forming cells, including red blood cells, white blood cells, and platelets. There are two types of bone marrow: red marrow, which is involved in blood cell production, and yellow marrow, which contains fatty tissue.
Red bone marrow contains hematopoietic stem cells, which can differentiate into various types of blood cells. These stem cells continuously divide and mature to produce new blood cells that are released into the circulation. Red blood cells carry oxygen throughout the body, white blood cells help fight infections, and platelets play a crucial role in blood clotting.
Bone marrow also serves as a site for immune cell development and maturation. It contains various types of immune cells, such as lymphocytes, macrophages, and dendritic cells, which help protect the body against infections and diseases.
Abnormalities in bone marrow function can lead to several medical conditions, including anemia, leukopenia, thrombocytopenia, and various types of cancer, such as leukemia and multiple myeloma. Bone marrow aspiration and biopsy are common diagnostic procedures used to evaluate bone marrow health and function.
A stem cell niche is a specific microenvironment in which stem cells reside, interact with surrounding cells and receive molecular signals that regulate their self-renewal, proliferation, differentiation, and survival. This specialized niche provides the necessary conditions for maintaining the undifferentiated state of stem cells and controlling their fate decisions. The components of a stem cell niche typically include various cell types (such as supporting cells, immune cells, and blood vessels), extracellular matrix proteins, signaling molecules, and physical factors like oxygen tension and mechanical stress. Together, these elements create a unique microenvironment that helps to preserve the functional integrity and potential of stem cells for tissue repair, regeneration, and homeostasis.
Cyclophosphamide is an alkylating agent, which is a type of chemotherapy medication. It works by interfering with the DNA of cancer cells, preventing them from dividing and growing. This helps to stop the spread of cancer in the body. Cyclophosphamide is used to treat various types of cancer, including lymphoma, leukemia, multiple myeloma, and breast cancer. It can be given orally as a tablet or intravenously as an injection.
Cyclophosphamide can also have immunosuppressive effects, which means it can suppress the activity of the immune system. This makes it useful in treating certain autoimmune diseases, such as rheumatoid arthritis and lupus. However, this immunosuppression can also increase the risk of infections and other side effects.
Like all chemotherapy medications, cyclophosphamide can cause a range of side effects, including nausea, vomiting, hair loss, fatigue, and increased susceptibility to infections. It is important for patients receiving cyclophosphamide to be closely monitored by their healthcare team to manage these side effects and ensure the medication is working effectively.
C57BL/6 (C57 Black 6) is an inbred strain of laboratory mouse that is widely used in biomedical research. The term "inbred" refers to a strain of animals where matings have been carried out between siblings or other closely related individuals for many generations, resulting in a population that is highly homozygous at most genetic loci.
The C57BL/6 strain was established in 1920 by crossing a female mouse from the dilute brown (DBA) strain with a male mouse from the black strain. The resulting offspring were then interbred for many generations to create the inbred C57BL/6 strain.
C57BL/6 mice are known for their robust health, longevity, and ease of handling, making them a popular choice for researchers. They have been used in a wide range of biomedical research areas, including studies of cancer, immunology, neuroscience, cardiovascular disease, and metabolism.
One of the most notable features of the C57BL/6 strain is its sensitivity to certain genetic modifications, such as the introduction of mutations that lead to obesity or impaired glucose tolerance. This has made it a valuable tool for studying the genetic basis of complex diseases and traits.
Overall, the C57BL/6 inbred mouse strain is an important model organism in biomedical research, providing a valuable resource for understanding the genetic and molecular mechanisms underlying human health and disease.
Homologous transplantation is a type of transplant surgery where organs or tissues are transferred between two genetically non-identical individuals of the same species. The term "homologous" refers to the similarity in structure and function of the donated organ or tissue to the recipient's own organ or tissue.
For example, a heart transplant from one human to another is an example of homologous transplantation because both organs are hearts and perform the same function. Similarly, a liver transplant, kidney transplant, lung transplant, and other types of organ transplants between individuals of the same species are also considered homologous transplantations.
Homologous transplantation is in contrast to heterologous or xenogeneic transplantation, where organs or tissues are transferred from one species to another, such as a pig heart transplanted into a human. Homologous transplantation is more commonly performed than heterologous transplantation due to the increased risk of rejection and other complications associated with xenogeneic transplants.
Cell differentiation is the process by which a less specialized cell, or stem cell, becomes a more specialized cell type with specific functions and structures. This process involves changes in gene expression, which are regulated by various intracellular signaling pathways and transcription factors. Differentiation results in the development of distinct cell types that make up tissues and organs in multicellular organisms. It is a crucial aspect of embryonic development, tissue repair, and maintenance of homeostasis in the body.
C-X-C chemokine receptor type 4 (CXCR4) is a type of protein found on the surface of some cells, including white blood cells, and is a type of G protein-coupled receptor (GPCR). CXCR4 binds specifically to the chemokine ligand CXCL12 (also known as stromal cell-derived factor 1, or SDF-1), which plays a crucial role in the trafficking and homing of immune cells, particularly hematopoietic stem cells and lymphocytes. The binding of CXCL12 to CXCR4 triggers various intracellular signaling pathways that regulate cell migration, proliferation, survival, and differentiation.
In addition to its role in the immune system, CXCR4 has been implicated in several physiological and pathological processes, such as embryonic development, neurogenesis, angiogenesis, cancer metastasis, and HIV infection. In cancer, the overexpression of CXCR4 or increased levels of its ligand CXCL12 have been associated with poor prognosis, tumor growth, and metastasis in various types of malignancies, including breast, lung, prostate, colon, and ovarian cancers. In HIV infection, the CXCR4 coreceptor, together with CD4, facilitates viral entry into host cells, particularly during the later stages of the disease when the virus shifts its preference from CCR5 to CXCR4 as a coreceptor.
In summary, CXCR4 is a cell-surface receptor that binds specifically to the chemokine ligand CXCL12 and plays essential roles in immune cell trafficking, hematopoiesis, cancer metastasis, and HIV infection.
'Cell lineage' is a term used in biology and medicine to describe the developmental history or relationship of a cell or group of cells to other cells, tracing back to the original progenitor or stem cell. It refers to the series of cell divisions and differentiation events that give rise to specific types of cells in an organism over time.
In simpler terms, cell lineage is like a family tree for cells, showing how they are related to each other through a chain of cell division and specialization events. This concept is important in understanding the development, growth, and maintenance of tissues and organs in living beings.
A "Blood Cell Count" is a medical laboratory test that measures the number of red blood cells (RBCs), white blood cells (WBCs), and platelets in a sample of blood. This test is often used as a part of a routine check-up or to help diagnose various medical conditions, such as anemia, infection, inflammation, and many others.
The RBC count measures the number of oxygen-carrying cells in the blood, while the WBC count measures the number of immune cells that help fight infections. The platelet count measures the number of cells involved in clotting. Abnormal results in any of these counts may indicate an underlying medical condition and further testing may be required for diagnosis and treatment.
Multiple myeloma is a type of cancer that forms in a type of white blood cell called a plasma cell. Plasma cells help your body fight infection by producing antibodies. In multiple myeloma, cancerous plasma cells accumulate in the bone marrow and crowd out healthy blood cells. Rather than producing useful antibodies, the cancer cells produce abnormal proteins that can cause complications such as kidney damage, bone pain and fractures.
Multiple myeloma is a type of cancer called a plasma cell neoplasm. Plasma cell neoplasms are diseases in which there is an overproduction of a single clone of plasma cells. In multiple myeloma, this results in the crowding out of normal plasma cells, red and white blood cells and platelets, leading to many of the complications associated with the disease.
The abnormal proteins produced by the cancer cells can also cause damage to organs and tissues in the body. These abnormal proteins can be detected in the blood or urine and are often used to monitor the progression of multiple myeloma.
Multiple myeloma is a relatively uncommon cancer, but it is the second most common blood cancer after non-Hodgkin lymphoma. It typically occurs in people over the age of 65, and men are more likely to develop multiple myeloma than women. While there is no cure for multiple myeloma, treatments such as chemotherapy, radiation therapy, and stem cell transplantation can help manage the disease and its symptoms, and improve quality of life.
Adult stem cells, also known as somatic stem cells, are undifferentiated cells found in specialized tissues or organs throughout the body of a developed organism. Unlike embryonic stem cells, which are derived from blastocysts and have the ability to differentiate into any cell type in the body (pluripotency), adult stem cells are typically more limited in their differentiation potential, meaning they can only give rise to specific types of cells within the tissue or organ where they reside.
Adult stem cells serve to maintain and repair tissues by replenishing dying or damaged cells. They can divide and self-renew over time, producing one daughter cell that remains a stem cell and another that differentiates into a mature, functional cell type. The most well-known adult stem cells are hematopoietic stem cells, which give rise to all types of blood cells, and mesenchymal stem cells, which can differentiate into various connective tissue cells such as bone, cartilage, fat, and muscle.
The potential therapeutic use of adult stem cells has been explored in various medical fields, including regenerative medicine and cancer therapy. However, their limited differentiation capacity and the challenges associated with isolating and expanding them in culture have hindered their widespread application. Recent advances in stem cell research, such as the development of techniques to reprogram adult cells into induced pluripotent stem cells (iPSCs), have opened new avenues for studying and harnessing the therapeutic potential of these cells.
Embryonic stem cells are a type of pluripotent stem cell that are derived from the inner cell mass of a blastocyst, which is a very early-stage embryo. These cells have the ability to differentiate into any cell type in the body, making them a promising area of research for regenerative medicine and the study of human development and disease. Embryonic stem cells are typically obtained from surplus embryos created during in vitro fertilization (IVF) procedures, with the consent of the donors. The use of embryonic stem cells is a controversial issue due to ethical concerns surrounding the destruction of human embryos.
Flow cytometry is a medical and research technique used to measure physical and chemical characteristics of cells or particles, one cell at a time, as they flow in a fluid stream through a beam of light. The properties measured include:
* Cell size (light scatter)
* Cell internal complexity (granularity, also light scatter)
* Presence or absence of specific proteins or other molecules on the cell surface or inside the cell (using fluorescent antibodies or other fluorescent probes)
The technique is widely used in cell counting, cell sorting, protein engineering, biomarker discovery and monitoring disease progression, particularly in hematology, immunology, and cancer research.
Cell movement, also known as cell motility, refers to the ability of cells to move independently and change their location within tissue or inside the body. This process is essential for various biological functions, including embryonic development, wound healing, immune responses, and cancer metastasis.
There are several types of cell movement, including:
1. **Crawling or mesenchymal migration:** Cells move by extending and retracting protrusions called pseudopodia or filopodia, which contain actin filaments. This type of movement is common in fibroblasts, immune cells, and cancer cells during tissue invasion and metastasis.
2. **Amoeboid migration:** Cells move by changing their shape and squeezing through tight spaces without forming protrusions. This type of movement is often observed in white blood cells (leukocytes) as they migrate through the body to fight infections.
3. **Pseudopodial extension:** Cells extend pseudopodia, which are temporary cytoplasmic projections containing actin filaments. These protrusions help the cell explore its environment and move forward.
4. **Bacterial flagellar motion:** Bacteria use a whip-like structure called a flagellum to propel themselves through their environment. The rotation of the flagellum is driven by a molecular motor in the bacterial cell membrane.
5. **Ciliary and ependymal movement:** Ciliated cells, such as those lining the respiratory tract and fallopian tubes, have hair-like structures called cilia that beat in coordinated waves to move fluids or mucus across the cell surface.
Cell movement is regulated by a complex interplay of signaling pathways, cytoskeletal rearrangements, and adhesion molecules, which enable cells to respond to environmental cues and navigate through tissues.
Stem Cell Factor (SCF), also known as Kit Ligand or Steel Factor, is a growth factor that plays a crucial role in the regulation of hematopoiesis, which is the process of producing various blood cells. It is a glycoprotein that binds to the c-Kit receptor found on hematopoietic stem cells and progenitor cells, promoting their survival, proliferation, and differentiation into mature blood cells.
SCF is involved in the development and function of several types of blood cells, including red blood cells, white blood cells, and platelets. It also plays a role in the maintenance and self-renewal of hematopoietic stem cells, which are essential for the continuous production of new blood cells throughout an individual's lifetime.
In addition to its role in hematopoiesis, SCF has been implicated in various other biological processes, such as melanogenesis, gametogenesis, and tissue repair and regeneration. Dysregulation of SCF signaling has been associated with several diseases, including certain types of cancer, bone marrow failure disorders, and autoimmune diseases.
Graft survival, in medical terms, refers to the success of a transplanted tissue or organ in continuing to function and integrate with the recipient's body over time. It is the opposite of graft rejection, which occurs when the recipient's immune system recognizes the transplanted tissue as foreign and attacks it, leading to its failure.
Graft survival depends on various factors, including the compatibility between the donor and recipient, the type and location of the graft, the use of immunosuppressive drugs to prevent rejection, and the overall health of the recipient. A successful graft survival implies that the transplanted tissue or organ has been accepted by the recipient's body and is functioning properly, providing the necessary physiological support for the recipient's survival and improved quality of life.
Etoposide is a chemotherapy medication used to treat various types of cancer, including lung cancer, testicular cancer, and certain types of leukemia. It works by inhibiting the activity of an enzyme called topoisomerase II, which is involved in DNA replication and transcription. By doing so, etoposide can interfere with the growth and multiplication of cancer cells.
Etoposide is often administered intravenously in a hospital or clinic setting, although it may also be given orally in some cases. The medication can cause a range of side effects, including nausea, vomiting, hair loss, and an increased risk of infection. It can also have more serious side effects, such as bone marrow suppression, which can lead to anemia, bleeding, and a weakened immune system.
Like all chemotherapy drugs, etoposide is not without risks and should only be used under the close supervision of a qualified healthcare provider. It is important for patients to discuss the potential benefits and risks of this medication with their doctor before starting treatment.
Recombinant proteins are artificially created proteins produced through the use of recombinant DNA technology. This process involves combining DNA molecules from different sources to create a new set of genes that encode for a specific protein. The resulting recombinant protein can then be expressed, purified, and used for various applications in research, medicine, and industry.
Recombinant proteins are widely used in biomedical research to study protein function, structure, and interactions. They are also used in the development of diagnostic tests, vaccines, and therapeutic drugs. For example, recombinant insulin is a common treatment for diabetes, while recombinant human growth hormone is used to treat growth disorders.
The production of recombinant proteins typically involves the use of host cells, such as bacteria, yeast, or mammalian cells, which are engineered to express the desired protein. The host cells are transformed with a plasmid vector containing the gene of interest, along with regulatory elements that control its expression. Once the host cells are cultured and the protein is expressed, it can be purified using various chromatography techniques.
Overall, recombinant proteins have revolutionized many areas of biology and medicine, enabling researchers to study and manipulate proteins in ways that were previously impossible.
Non-Hodgkin lymphoma (NHL) is a type of cancer that originates in the lymphatic system, which is part of the immune system. It involves the abnormal growth and proliferation of malignant lymphocytes (a type of white blood cell), leading to the formation of tumors in lymph nodes, spleen, bone marrow, or other organs. NHL can be further classified into various subtypes based on the specific type of lymphocyte involved and its characteristics.
The symptoms of Non-Hodgkin lymphoma may include:
* Painless swelling of lymph nodes in the neck, armpits, or groin
* Persistent fatigue
* Unexplained weight loss
* Fever
* Night sweats
* Itchy skin
The exact cause of Non-Hodgkin lymphoma is not well understood, but it has been associated with certain risk factors such as age (most common in people over 60), exposure to certain chemicals, immune system deficiencies, and infection with viruses like Epstein-Barr virus or HIV.
Treatment for Non-Hodgkin lymphoma depends on the stage and subtype of the disease, as well as the patient's overall health. Treatment options may include chemotherapy, radiation therapy, immunotherapy, targeted therapy, stem cell transplantation, or a combination of these approaches. Regular follow-up care is essential to monitor the progression of the disease and manage any potential long-term side effects of treatment.
Transplantation conditioning, also known as preparative regimen or immunoablative therapy, refers to the use of various treatments prior to transplantation of cells, tissues or organs. The main goal of transplantation conditioning is to suppress the recipient's immune system, allowing for successful engraftment and minimizing the risk of rejection of the donor tissue.
There are two primary types of transplantation conditioning: myeloablative and non-myeloablative.
1. Myeloablative conditioning is a more intensive regimen that involves the use of high-dose chemotherapy, radiation therapy or both. This approach eliminates not only immune cells but also stem cells in the bone marrow, requiring the recipient to receive a hematopoietic cell transplant (HCT) from the donor to reconstitute their blood and immune system.
2. Non-myeloablative conditioning is a less intensive regimen that primarily targets immune cells while sparing the stem cells in the bone marrow. This approach allows for mixed chimerism, where both recipient and donor immune cells coexist, reducing the risk of severe complications associated with myeloablative conditioning.
The choice between these two types of transplantation conditioning depends on various factors, including the type of transplant, patient's age, overall health, and comorbidities. Both approaches carry risks and benefits, and the decision should be made carefully by a multidisciplinary team of healthcare professionals in consultation with the patient.
"Cells, cultured" is a medical term that refers to cells that have been removed from an organism and grown in controlled laboratory conditions outside of the body. This process is called cell culture and it allows scientists to study cells in a more controlled and accessible environment than they would have inside the body. Cultured cells can be derived from a variety of sources, including tissues, organs, or fluids from humans, animals, or cell lines that have been previously established in the laboratory.
Cell culture involves several steps, including isolation of the cells from the tissue, purification and characterization of the cells, and maintenance of the cells in appropriate growth conditions. The cells are typically grown in specialized media that contain nutrients, growth factors, and other components necessary for their survival and proliferation. Cultured cells can be used for a variety of purposes, including basic research, drug development and testing, and production of biological products such as vaccines and gene therapies.
It is important to note that cultured cells may behave differently than they do in the body, and results obtained from cell culture studies may not always translate directly to human physiology or disease. Therefore, it is essential to validate findings from cell culture experiments using additional models and ultimately in clinical trials involving human subjects.
Pluripotent stem cells are a type of undifferentiated stem cell that have the ability to differentiate into any cell type of the three germ layers (endoderm, mesoderm, and ectoderm) of a developing embryo. These cells can give rise to all the cell types that make up the human body, with the exception of those that form the extra-embryonic tissues such as the placenta.
Pluripotent stem cells are characterized by their ability to self-renew, which means they can divide and produce more pluripotent stem cells, and differentiate, which means they can give rise to specialized cell types with specific functions. Pluripotent stem cells can be derived from embryos at the blastocyst stage of development or generated in the lab through a process called induced pluripotency, where adult cells are reprogrammed to have the properties of embryonic stem cells.
Pluripotent stem cells hold great promise for regenerative medicine and tissue engineering because they can be used to generate large numbers of specific cell types that can potentially replace or repair damaged or diseased tissues in the body. However, their use is still a subject of ethical debate due to concerns about the source of embryonic stem cells and the potential risks associated with their use in clinical applications.
Multipotent stem cells are a type of stem cell that have the ability to differentiate into multiple cell types, but are more limited than pluripotent stem cells. These stem cells are found in various tissues and organs throughout the body, including bone marrow, adipose tissue, and dental pulp. They can give rise to a number of different cell types within their own germ layer (endoderm, mesoderm, or ectoderm), but cannot cross germ layer boundaries. For example, multipotent stem cells found in bone marrow can differentiate into various blood cells such as red and white blood cells, but they cannot differentiate into nerve cells or liver cells. These stem cells play important roles in tissue repair and regeneration, and have potential therapeutic applications in regenerative medicine.
Bone marrow transplantation (BMT) is a medical procedure in which damaged or destroyed bone marrow is replaced with healthy bone marrow from a donor. Bone marrow is the spongy tissue inside bones that produces blood cells. The main types of BMT are autologous, allogeneic, and umbilical cord blood transplantation.
In autologous BMT, the patient's own bone marrow is used for the transplant. This type of BMT is often used in patients with lymphoma or multiple myeloma who have undergone high-dose chemotherapy or radiation therapy to destroy their cancerous bone marrow.
In allogeneic BMT, bone marrow from a genetically matched donor is used for the transplant. This type of BMT is often used in patients with leukemia, lymphoma, or other blood disorders who have failed other treatments.
Umbilical cord blood transplantation involves using stem cells from umbilical cord blood as a source of healthy bone marrow. This type of BMT is often used in children and adults who do not have a matched donor for allogeneic BMT.
The process of BMT typically involves several steps, including harvesting the bone marrow or stem cells from the donor, conditioning the patient's body to receive the new bone marrow or stem cells, transplanting the new bone marrow or stem cells into the patient's body, and monitoring the patient for signs of engraftment and complications.
BMT is a complex and potentially risky procedure that requires careful planning, preparation, and follow-up care. However, it can be a life-saving treatment for many patients with blood disorders or cancer.
Graft-versus-host disease (GVHD) is a condition that can occur after an allogeneic hematopoietic stem cell transplantation (HSCT), where the donated immune cells (graft) recognize the recipient's tissues (host) as foreign and attack them. This results in inflammation and damage to various organs, particularly the skin, gastrointestinal tract, and liver.
Acute GVHD typically occurs within 100 days of transplantation and is characterized by symptoms such as rash, diarrhea, and liver dysfunction. Chronic GVHD, on the other hand, can occur after 100 days or even years post-transplant and may present with a wider range of symptoms, including dry eyes and mouth, skin changes, lung involvement, and issues with mobility and flexibility in joints.
GVHD is a significant complication following allogeneic HSCT and can have a substantial impact on the patient's quality of life and overall prognosis. Preventative measures, such as immunosuppressive therapy, are often taken to reduce the risk of GVHD, but its management remains a challenge in transplant medicine.
Cell proliferation is the process by which cells increase in number, typically through the process of cell division. In the context of biology and medicine, it refers to the reproduction of cells that makes up living tissue, allowing growth, maintenance, and repair. It involves several stages including the transition from a phase of quiescence (G0 phase) to an active phase (G1 phase), DNA replication in the S phase, and mitosis or M phase, where the cell divides into two daughter cells.
Abnormal or uncontrolled cell proliferation is a characteristic feature of many diseases, including cancer, where deregulated cell cycle control leads to excessive and unregulated growth of cells, forming tumors that can invade surrounding tissues and metastasize to distant sites in the body.
Melphalan is an antineoplastic agent, specifically an alkylating agent. It is used in the treatment of multiple myeloma and other types of cancer. The medical definition of Melphalan is:
A nitrogen mustard derivative that is used as an alkylating agent in the treatment of cancer, particularly multiple myeloma and ovarian cancer. Melphalan works by forming covalent bonds with DNA, resulting in cross-linking of the double helix and inhibition of DNA replication and transcription. This ultimately leads to cell cycle arrest and apoptosis (programmed cell death) in rapidly dividing cells, such as cancer cells.
Melphalan is administered orally or intravenously, and its use is often accompanied by other anticancer therapies, such as radiation therapy or chemotherapy. Common side effects of Melphalan include nausea, vomiting, diarrhea, and bone marrow suppression, which can lead to anemia, neutropenia, and thrombocytopenia. Other potential side effects include hair loss, mucositis, and secondary malignancies.
It is important to note that Melphalan should be used under the close supervision of a healthcare professional, as it can cause serious adverse reactions if not administered correctly.
Combined modality therapy (CMT) is a medical treatment approach that utilizes more than one method or type of therapy simultaneously or in close succession, with the goal of enhancing the overall effectiveness of the treatment. In the context of cancer care, CMT often refers to the combination of two or more primary treatment modalities, such as surgery, radiation therapy, and systemic therapies (chemotherapy, immunotherapy, targeted therapy, etc.).
The rationale behind using combined modality therapy is that each treatment method can target cancer cells in different ways, potentially increasing the likelihood of eliminating all cancer cells and reducing the risk of recurrence. The specific combination and sequence of treatments will depend on various factors, including the type and stage of cancer, patient's overall health, and individual preferences.
For example, a common CMT approach for locally advanced rectal cancer may involve preoperative (neoadjuvant) chemoradiation therapy, followed by surgery to remove the tumor, and then postoperative (adjuvant) chemotherapy. This combined approach allows for the reduction of the tumor size before surgery, increases the likelihood of complete tumor removal, and targets any remaining microscopic cancer cells with systemic chemotherapy.
It is essential to consult with a multidisciplinary team of healthcare professionals to determine the most appropriate CMT plan for each individual patient, considering both the potential benefits and risks associated with each treatment method.
Treatment outcome is a term used to describe the result or effect of medical treatment on a patient's health status. It can be measured in various ways, such as through symptoms improvement, disease remission, reduced disability, improved quality of life, or survival rates. The treatment outcome helps healthcare providers evaluate the effectiveness of a particular treatment plan and make informed decisions about future care. It is also used in clinical research to compare the efficacy of different treatments and improve patient care.
Mesenchymal Stromal Cells (MSCs) are a type of adult stem cells found in various tissues, including bone marrow, adipose tissue, and umbilical cord blood. They have the ability to differentiate into multiple cell types, such as osteoblasts, chondrocytes, and adipocytes, under specific conditions. MSCs also possess immunomodulatory properties, making them a promising tool in regenerative medicine and therapeutic strategies for various diseases, including autoimmune disorders and tissue injuries. It is important to note that the term "Mesenchymal Stem Cells" has been replaced by "Mesenchymal Stromal Cells" in the scientific community to better reflect their biological characteristics and potential functions.
Fetal blood refers to the blood circulating in a fetus during pregnancy. It is essential for the growth and development of the fetus, as it carries oxygen and nutrients from the placenta to the developing tissues and organs. Fetal blood also removes waste products, such as carbon dioxide, from the fetal tissues and transports them to the placenta for elimination.
Fetal blood has several unique characteristics that distinguish it from adult blood. For example, fetal hemoglobin (HbF) is the primary type of hemoglobin found in fetal blood, whereas adults primarily have adult hemoglobin (HbA). Fetal hemoglobin has a higher affinity for oxygen than adult hemoglobin, which allows it to more efficiently extract oxygen from the maternal blood in the placenta.
Additionally, fetal blood contains a higher proportion of reticulocytes (immature red blood cells) and nucleated red blood cells compared to adult blood. These differences reflect the high turnover rate of red blood cells in the developing fetus and the need for rapid growth and development.
Examination of fetal blood can provide important information about the health and well-being of the fetus during pregnancy. For example, fetal blood sampling (also known as cordocentesis or percutaneous umbilical blood sampling) can be used to diagnose genetic disorders, infections, and other conditions that may affect fetal development. However, this procedure carries risks, including preterm labor, infection, and fetal loss, and is typically only performed when there is a significant risk of fetal compromise or when other diagnostic tests have been inconclusive.
Antineoplastic combined chemotherapy protocols refer to a treatment plan for cancer that involves the use of more than one antineoplastic (chemotherapy) drug given in a specific sequence and schedule. The combination of drugs is used because they may work better together to destroy cancer cells compared to using a single agent alone. This approach can also help to reduce the likelihood of cancer cells becoming resistant to the treatment.
The choice of drugs, dose, duration, and frequency are determined by various factors such as the type and stage of cancer, patient's overall health, and potential side effects. Combination chemotherapy protocols can be used in various settings, including as a primary treatment, adjuvant therapy (given after surgery or radiation to kill any remaining cancer cells), neoadjuvant therapy (given before surgery or radiation to shrink the tumor), or palliative care (to alleviate symptoms and prolong survival).
It is important to note that while combined chemotherapy protocols can be effective in treating certain types of cancer, they can also cause significant side effects, including nausea, vomiting, hair loss, fatigue, and an increased risk of infection. Therefore, patients undergoing such treatment should be closely monitored and managed by a healthcare team experienced in administering chemotherapy.
Cell separation is a process used to separate and isolate specific cell types from a heterogeneous mixture of cells. This can be accomplished through various physical or biological methods, depending on the characteristics of the cells of interest. Some common techniques for cell separation include:
1. Density gradient centrifugation: In this method, a sample containing a mixture of cells is layered onto a density gradient medium and then centrifuged. The cells are separated based on their size, density, and sedimentation rate, with denser cells settling closer to the bottom of the tube and less dense cells remaining near the top.
2. Magnetic-activated cell sorting (MACS): This technique uses magnetic beads coated with antibodies that bind to specific cell surface markers. The labeled cells are then passed through a column placed in a magnetic field, which retains the magnetically labeled cells while allowing unlabeled cells to flow through.
3. Fluorescence-activated cell sorting (FACS): In this method, cells are stained with fluorochrome-conjugated antibodies that recognize specific cell surface or intracellular markers. The stained cells are then passed through a laser beam, which excites the fluorophores and allows for the detection and sorting of individual cells based on their fluorescence profile.
4. Filtration: This simple method relies on the physical size differences between cells to separate them. Cells can be passed through filters with pore sizes that allow smaller cells to pass through while retaining larger cells.
5. Enzymatic digestion: In some cases, cells can be separated by enzymatically dissociating tissues into single-cell suspensions and then using various separation techniques to isolate specific cell types.
These methods are widely used in research and clinical settings for applications such as isolating immune cells, stem cells, or tumor cells from biological samples.
Proto-oncogene proteins c-kit, also known as CD117 or stem cell factor receptor, are transmembrane receptor tyrosine kinases that play crucial roles in various biological processes, including cell survival, proliferation, differentiation, and migration. They are encoded by the c-KIT gene located on human chromosome 4q12.
These proteins consist of an extracellular ligand-binding domain, a transmembrane domain, and an intracellular tyrosine kinase domain. The binding of their ligand, stem cell factor (SCF), leads to receptor dimerization, autophosphorylation, and activation of several downstream signaling pathways such as PI3K/AKT, MAPK/ERK, and JAK/STAT.
Abnormal activation or mutation of c-kit proto-oncogene proteins has been implicated in the development and progression of various malignancies, including gastrointestinal stromal tumors (GISTs), acute myeloid leukemia (AML), mast cell diseases, and melanoma. Targeted therapies against c-kit, such as imatinib mesylate (Gleevec), have shown promising results in the treatment of these malignancies.
Hematologic neoplasms, also known as hematological malignancies, are a group of diseases characterized by the uncontrolled growth and accumulation of abnormal blood cells or bone marrow cells. These disorders can originate from the myeloid or lymphoid cell lines, which give rise to various types of blood cells, including red blood cells, white blood cells, and platelets.
Hematologic neoplasms can be broadly classified into three categories:
1. Leukemias: These are cancers that primarily affect the bone marrow and blood-forming tissues. They result in an overproduction of abnormal white blood cells, which interfere with the normal functioning of the blood and immune system. There are several types of leukemia, including acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), acute myeloid leukemia (AML), and chronic myeloid leukemia (CML).
2. Lymphomas: These are cancers that develop from the lymphatic system, which is a part of the immune system responsible for fighting infections. Lymphomas can affect lymph nodes, spleen, bone marrow, and other organs. The two main types of lymphoma are Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL).
3. Myelomas: These are cancers that arise from the plasma cells, a type of white blood cell responsible for producing antibodies. Multiple myeloma is the most common type of myeloma, characterized by an excessive proliferation of malignant plasma cells in the bone marrow, leading to the production of abnormal amounts of monoclonal immunoglobulins (M proteins) and bone destruction.
Hematologic neoplasms can have various symptoms, such as fatigue, weakness, frequent infections, easy bruising or bleeding, weight loss, swollen lymph nodes, and bone pain. The diagnosis typically involves a combination of medical history, physical examination, laboratory tests, imaging studies, and sometimes bone marrow biopsy. Treatment options depend on the type and stage of the disease and may include chemotherapy, radiation therapy, targeted therapy, immunotherapy, stem cell transplantation, or a combination of these approaches.
Dexamethasone is a type of corticosteroid medication, which is a synthetic version of a natural hormone produced by the adrenal glands. It is often used to reduce inflammation and suppress the immune system in a variety of medical conditions, including allergies, asthma, rheumatoid arthritis, and certain skin conditions.
Dexamethasone works by binding to specific receptors in cells, which triggers a range of anti-inflammatory effects. These include reducing the production of chemicals that cause inflammation, suppressing the activity of immune cells, and stabilizing cell membranes.
In addition to its anti-inflammatory effects, dexamethasone can also be used to treat other medical conditions, such as certain types of cancer, brain swelling, and adrenal insufficiency. It is available in a variety of forms, including tablets, liquids, creams, and injectable solutions.
Like all medications, dexamethasone can have side effects, particularly if used for long periods of time or at high doses. These may include mood changes, increased appetite, weight gain, acne, thinning skin, easy bruising, and an increased risk of infections. It is important to follow the instructions of a healthcare provider when taking dexamethasone to minimize the risk of side effects.
The hematopoietic system is the group of tissues and organs in the body that are responsible for the production and maturation of blood cells. These include:
1. Bone marrow: The spongy tissue inside some bones, like the hips and thighs, where most blood cells are produced.
2. Spleen: An organ located in the upper left part of the abdomen that filters the blood, stores red and white blood cells, and removes waste products.
3. Liver: A large organ in the upper right part of the abdomen that filters blood, detoxifies harmful substances, produces bile to aid in digestion, and stores some nutrients like glucose and iron.
4. Lymph nodes: Small glands found throughout the body, especially in the neck, armpits, and groin, that filter lymph fluid and help fight infection.
5. Thymus: A small organ located in the chest, between the lungs, that helps develop T-cells, a type of white blood cell that fights infection.
The hematopoietic system produces three main types of cells:
1. Red blood cells (erythrocytes): Carry oxygen from the lungs to the body's tissues and carbon dioxide from the tissues to the lungs.
2. White blood cells (leukocytes): Help fight infection and are part of the body's immune system.
3. Platelets (thrombocytes): Small cell fragments that help form blood clots to stop bleeding.
Disorders of the hematopoietic system can lead to conditions such as anemia, leukemia, and lymphoma.