• The laws surrounding the two differ because while both have similar capacities in differentiation, their modes of derivation are not. (wikipedia.org)
  • Stem cells are not specialized and the process of their specialization is called differentiation. (benthamscience.com)
  • Derivation and differentiation of haploid human embryonic stem cells. (nature.com)
  • The ICOC has approved a very well-balanced portfolio of research proposals, including those aimed at understanding stem cell differentiation and identifying new ways of obtaining hESCs, and many that target specific diseases," Hall said. (ca.gov)
  • It has been reported that Sirtuin 6 (Sirt6), a member of the sirtuin family of NAD + -dependent protein deacetylases, is involved in embryonic stem cell differentiation. (biomedcentral.com)
  • OP9 feeder cell co-culture system was used to measure the hematopoietic differentiation from mouse ES and iPS cells. (biomedcentral.com)
  • Furthermore, we showed that Sirt6-null iPS-like cell line has intrinsically a differentiation defect even though the establishment of normal self-renewal. (biomedcentral.com)
  • To further understand the epigenetic regulators for specific lineage differentiation from iPS cell would have great significance for potential regeneration therapy and human disease modeling [ 8 ]. (biomedcentral.com)
  • During the preparation of our manuscript, another group reported that Sirt6 knockout ES cells skewed towards neuroectoderm differentiation [ 20 ]. (biomedcentral.com)
  • But the exact role of Sirt6 in mouse somatic reprogramming and iPS cell differentiation remains unrevealed. (biomedcentral.com)
  • Ideally, iPSC-based therapies in the future will rely on the isolation of skin fibroblasts or keratinocytes, their reprogramming into iPSCs, and the correction of the genetic defect followed by differentiation into the desired cell type and transplantation. (biomedcentral.com)
  • Stability of Imprinting and Differentiation Capacity in Naïve Human Cells Induced by Chemical Inhibition of CDK8 and CDK19. (axonmedchem.com)
  • Stem and progenitor cell populations are often heterogeneous, which may reflect stem cell subsets that express subtly different properties, including different propensities for lineage selection upon differentiation, yet remain able to interconvert. (lu.se)
  • A key challenge is to understand how state, but must also afford flexibility in cell-fate choice to permit the different cell-fate options confronting stem and progenitor cell-type diversification and differentiation in response to cells are selected and coordinated such that adoption of a given intrinsic cues or extrinsic signals. (lu.se)
  • Evidence the fate of stem cells has broad ramifications for biomedical suggests that during development or differentiation, cells make science from elucidating the causes of cancer to the use of very precise transitions between apparently stable ``network stem cells in regenerative medicine. (lu.se)
  • While more and more long intergenic non-coding RNAs (lincRNAs) were identified to take important roles in both maintaining pluripotency and regulating differentiation, how these lincRNAs may define and drive cell fate decisions on a global scale are still mostly elusive. (biomedcentral.com)
  • Our research focuses on developmental pathways that regulate hematopoietic cell growth and differentiation and are disrupted in the course of neoplastic transformation, particularly in leukemias and lymphomas. (stanford.edu)
  • To establish protocols for the safe and efficient differentiation of healthy cells for therapies, we must develop a better understanding of the dynamic continuum of metabolic states that span pluripotency and differentiation, and how to influence them. (conditionmed.org)
  • The AF form of SALSA had a more intact structure and contained peptides from the zona pellucida domain, which is involved in cell differentiation and oligomerization. (researchgate.net)
  • The established dogma has however been challenged by recent findings suggesting that multipotent stem cells have a broader differentiation potential than previously thought. (biomedcentral.com)
  • Dazl can regulate the expression, transport and localization of target mRNAs of proteins which control the differentiation, growth and maturation of germ cells. (ijbs.com)
  • Depending on the source, stem cells can be classified into two broad categories i.e. embryonic stem cells that are derived from embryos and non-embryonic stem cells that are derived from adult and fetal tissues. (benthamscience.com)
  • Mouse nuclear transfer embryonic stem cells (NT-ESCs) were first established in 2000, and then proved to be able to differentiate either in vivo or in vitro, and give rise to individual tissues through germ line transmission or tetraploid complementation. (benthamscience.com)
  • Today, we can derive stem cells from a range of adult and newborn tissues: liver cells, kidney cells, brain cells, fat cells, and umbilical cord blood. (eppc.org)
  • Embryo-like models with spatially organized morphogenesis and structure of all defining embryonic and extra-embryonic tissues of the post-implantation human conceptus (that is, the embryonic disc, the bilaminar disc, the yolk sac, the chorionic sac and the surrounding trophoblast layer) remain lacking 1 , 2 . (nature.com)
  • Much of this process relies on the morphogenesis of the extra-embryonic tissues and the effect this has on the organization of embryonic cells. (nature.com)
  • In addition, as the genetic identity of the donor egg from which the ESCs are derived most likely will differ from that of potential recipients, patients who receive ESC-derived cells or tissues may face the same complications that result from organ transplantation (for example, immunorejection, graft-versus-host disease, and need for immunosuppression). (biomedcentral.com)
  • In mammals, physiological Wnt signaling is intimately involved with the biology of adult stem cells and self-renewing tissues (18,19). (hubrecht.eu)
  • These epithelial organoid cultures are genetically and phenotypically extremely stable, allowing transplantation of the cultured offspring of a single stem cell, as well as disease modeling by growing organoids directly from diseased patient tissues (32, 47, 53). (hubrecht.eu)
  • Mechanochemical Principles of Spatial and Temporal Patterns in Cells and Tissues. (mpi-cbg.de)
  • Patterns are ubiquitous in living systems and underlie the dynamic organization of cells, tissues, and embryos. (mpi-cbg.de)
  • Stem cell technologies promise to be the next transformative medical technology offering therapies for conditions and diseases that are currently beyond medical science by creating replacement or supplementary tissues for a patient. (schlich.co.uk)
  • Therapeutic Cloning - Use of a donor cell to create pluripotent stem cells suitable for growing tissues for implantation into the donor or other patient. (schlich.co.uk)
  • reagents made using a patient's own cells used to regenerate disease or damaged tissues 14,15 , once the stuff of science fiction, may become science fact. (schlich.co.uk)
  • However, the mice were grossly normal when dab2 deletion was restricted to the embryo proper and the gene was retained in extraembryonic tissues using Meox2-Cre and Sox2-Cre. (biomedcentral.com)
  • A few of the cells in the inner cell mass will develop into the foetus, whereas the rest will form the placenta and other supporting tissues needed for foetal development in the uterus. (biomedcentral.com)
  • The stem cells suits human needs, does not cause harm and can be obtained from both adult and fetal does not conflict with religious beliefs, it has tissues, umbilical cord and early embryos. (who.int)
  • Micha's interest lies in discovering mechanisms that regulate the formation of the embryonic tissues using iPS cells, in order to create novel models for human disease and drug development with emphasis on neurodegeneration. (universiteitleiden.nl)
  • The institute encompasses 23 research groups that perform fundamental, multidisciplinary research on healthy and diseased cells, tissues and organisms. (maquisadeoccidente.com)
  • Therefore, we propose that damage to and subsequent release of mtDNA elicits a protective signalling response that enhances nDNA repair in cells and tissues, suggesting that mtDNA is a genotoxic stress sentinel. (regenerativemedicine.net)
  • Because ES cells are cultured from the embryoblast 4-5 days after fertilization, harvesting them is most often done from donated embryos from in vitro fertilization (IVF) clinics. (wikipedia.org)
  • France prohibits reproductive cloning and embryo creation for research purposes, but enacted laws (with a sunset provision expiring in 2009) to allow scientists to conduct stem cell research on imported a large amount of embryos from in vitro fertilization treatments. (wikipedia.org)
  • … "human clone" means an embryo that, as a result of the manipulation of human reproductive material or an in vitro embryo, contains a diploid set of chromosomes obtained from a single - living or deceased - human being, fetus, or embryo. (hinxtongroup.org)
  • SSCs can be isolated from the testis and cultured in vitro for longterm periods in the presence of feeder cells (often mouse embryonic fibroblasts). (molcells.org)
  • Although several in vitro SSC culture systems without feeder cells have been previously described, our Matrigel-based feeder-free culture system is time- and cost- effective, and preserves self-renewability of SSCs. (molcells.org)
  • Established SSCs are useful stem cell lines that allow not only to study basic reproductive biology but also to develop an in vitro model for applications in assisted reproductive medicine. (molcells.org)
  • When primary SSCs are derived from the testis and proliferated in vitro , mouse embryonic fibroblasts (MEFs) are the most commonly used feeder cells that play a role of such microniche by allowing secure attachment and proliferation of SSCs. (molcells.org)
  • Cells are collected from donor (a) and cultured in vitro (b). (biomedcentral.com)
  • The somatic cell and the oocyte is then fused (f) and the embryos is allowed to develop to a blastocyst in vitro (g). (biomedcentral.com)
  • Lgr5 resides in Wnt receptor complexes and mediates signaling of the Wnt-agonistic R-spondins (31), explaining the unique dependence of Lgr5 stem cells on secreted R-spondins in vivo and in vitro. (hubrecht.eu)
  • Moreover, the knockdown of circ_0082319 might repress HCC cell proliferation, invasion, angiogenesis, and induce apoptosis in vitro. (bvsalud.org)
  • In vitro studies indicate that Dab2 establishes epithelial cell polarity and organization by directing endocytic trafficking of membrane glycoproteins. (biomedcentral.com)
  • We discuss what is known about the distinct metabolic states captured in vitro by the 2-cell-like, naïve, blastocyst-like, formative, and primed states of pluripotency. (conditionmed.org)
  • 2019). Akin to the dynamic nutrient requirements of the developing embryo, discrete in vitro cell states have distinct metabolic profiles (Zhou et al. (conditionmed.org)
  • It is only through understanding embryonic metabolism and development that we can derive and maintain different in vitro stem cell states for disease modeling and therapies. (conditionmed.org)
  • In vitro fertilized (IVF) embryos were cultured in the presence of dimethyl sulfoxide or inhibitors of MAP2K (0.4 μM PD0325901) and GSK3 (3 μM CHIR99021) from the zygote (Day 1) stage. (bioone.org)
  • Assisted reproductive techniques for canines: preservation of genetic material in domestic dogs [3] "Assisted reproductive techniques (ARTs), such as artificial insemination, in vitro fertilization, and cryopreservation of gametes/zygotes, have been developed to improve breeding and reproduction of livestock and for the treatment of human infertility. (edu.au)
  • Belgium bans reproductive cloning but allows therapeutic cloning of embryos. (wikipedia.org)
  • Sweden forbids reproductive cloning, but allows therapeutic cloning and authorized a stem cell bank. (wikipedia.org)
  • Kuldip S. Sidhu , " Frontiers in Pluripotent Stem Cells Research and Therapeutic Potentials Bench-to-Bedside ", Bentham Science Publishers (2012). (benthamscience.com)
  • Embryonic stem cells (ESCs) can grow infinitely and give rise to all types of cells in human body, thus of tremendous therapeutic potentials for a variety of diseases, such as Parkinson's disease, spinal cord injury, and diabetes. (benthamscience.com)
  • Under such circumstances, the idea of "therapeutic cloning" was proposed, indicating the generation of ESCs from SCNT embryos for therapeutic purpose. (benthamscience.com)
  • If the cloned human organism is to be experimented upon and destroyed, the process is often called "therapeutic cloning. (cbc-network.org)
  • But adult stem cells also raise some interesting ethical dilemmas alongside their great therapeutic promise. (eppc.org)
  • Finally, and inexorably, a true professional scientist poses clearly challenging questions to his research colleagues, and to the scientific enterprise in general, about the dubious "scientific" justification for the current rush to clone human beings - for both "therapeutic" and for "reproductive" purposes. (lifeissues.net)
  • But he is equally concerned about the unethical aspects inherent in the rush to perform " therapeutic " human cloning research, including the abuses to all vulnerable human patients who would be required to participate in clinical trials. (lifeissues.net)
  • In particular, scientific developments in areas such as iPS cells open new possibilities of research and, at mid term, of therapeutic applications, but they also bring new ethical challenges and problems requiring further reflection and debate. (lifeissues.net)
  • HuR-mediated circ_0082319 might accelerate HCC cell proliferation, invasion, angiogenesis, and suppress apoptosis by the miR-505-3p/PTK2 axis, hinting at a promising therapeutic target for HCC treatment. (bvsalud.org)
  • Therapeutic cloning possesses enormous potential for revolutionizing medical and thera- peutic techniques. (who.int)
  • This is therapeutic cloning. (who.int)
  • This cell then has therapeutic cloning: the global the capacity to divide and grow into an exact replica of the original from whom the debate somatic cell was taken. (who.int)
  • The signatories' action is a collective response to this week's meeting in Paris of UNESCO's international bioethics committee , which is discussing whether so-called therapeutic cloning should be banned worldwide. (blogspot.com)
  • If it is to be brought to birth, the process is usually called "reproductive cloning. (cbc-network.org)
  • But we can only wonder about the ethical propriety of producing the first human child with this technique, knowing that the hoped-for newborn would be a reproductive experiment, one that may end initially in numerous fetal failures. (eppc.org)
  • Agreeing with the premise of an earlier article in the same journal, he agrees that we "must not let our debate get completely derailed by vested interests, whether politically or economically motivated", and that the failure to find global agreement on human cloning at the U.N. could result in "reproductive" human cloning [and all the abuses of women that would entail]. (lifeissues.net)
  • But what is not getting such wide reporting is the use of pluripotent stem cells (as well as many other types of cells and genetic engineering techniques) for reproductive purposes . (lifeissues.net)
  • 3. National regulations of governance of human cloning and embryo research in general adopted so far confirm the convergence of views of the refusal to adopt legislation or guidelines permitting reproductive cloning , while they still show variations on the legitimacy of human cloning carried out as part of research agendas. (lifeissues.net)
  • Reproductive Cloning - Use of a donor cell to create a new human genetically identical to the donor. (schlich.co.uk)
  • Here, we present a comprehensive update of this ontology pertaining to mouse LUT, genital tubercle and associated reproductive structures (E10.5 to adult). (atlas-d2k.org)
  • Ontology changes include new structures, tissue layers and cell types within the LUT, external genitalia and lower reproductive structures. (atlas-d2k.org)
  • Cloning technology, however, is perceived as having the potential for reproductive cloning, which raises serious ethical and moral concerns. (who.int)
  • Reproductive cloning versus germ cell (egg, ovum). (who.int)
  • Research advocates attack President Bush for "banning stem cell research," while pro-life advocates lament a Republican administration and Congress that have banned nothing-not embryo destruction, not human cloning, not fetal farming, not genetic engineering. (eppc.org)
  • Tissue-specific stem cells (also known as Somatic Stem Cells) that appear during fetal development and remain in the body throughout life. (edu.au)
  • The aim of this study was to morphologically examine nephrogenesis in fetal human kidneys from 20 to 41weeks of gestation. (atlas-d2k.org)
  • Daz is found in fetal gonocytes, spermatogonia and spermatocytes of adult testes. (ijbs.com)
  • Stem cells are emerging as an important source of material for diseases in regenerative medicine. (benthamscience.com)
  • The study of biology of stem cells is the hallmark of the recent emerging field of regenerative medicine and medical biotechnology. (benthamscience.com)
  • The holy grail of regenerative medicine-whatever one's ethical beliefs about destroying embryos-is to "reprogram" regular cells from one's own body so that individuals can be the source of their own rejection-proof therapies. (eppc.org)
  • The use of various types of stem cells for research purposes to make disease "models" in the lab for regenerative medicine and for "therapies" to cure sick patients for diseases is constantly in the news. (lifeissues.net)
  • The 29-member Independent Citizens Oversight Committee (ICOC), governing board of the California Institute for Regenerative Medicine (CIRM), today approved 29 Comprehensive Research Grants for approximately $74.6 million over four years, to accomplished stem cell investigators at academic and non-profit research centers throughout the state. (ca.gov)
  • Derivation of autologous induced pluripotent stem cells (iPSCs) through direct reprogramming of easily accessible somatic cells holds the potential to transform the field of regenerative medicine. (biomedcentral.com)
  • Although this technology holds the potential to revolutionize drug discovery and regenerative medicine, important technical issues associated with the derivation of iPSCs still hinder its clinical translation. (biomedcentral.com)
  • Prof. Dr. Micha Drukker is a professor of Stem Cell Biology, Models and Regenerative medicine at the Division of Drug Discovery & Safety. (universiteitleiden.nl)
  • It is the policy of Washington state that research involving the derivation and use of human embryonic stem cells, human embryonic germ cells, and human adult stem cells from any source, including somatic cell nuclear transplantation , is permitted upon full consideration of the ethical and medical implications of this research. (cbc-network.org)
  • Tudor-related proteins TDRD1/MTR-1, TDRD6 and TDRD7/TRAP: domain composition, intracellular localization, and function in male germ cells in mice. (shengsci.com)
  • In mice, nuage that is prominent in postnatal male germ cells is also called intermitochondrial cement or chromatoid bodies. (shengsci.com)
  • Spermatogonial stem cells (SSCs, also called germline stem cells) are self-renewing unipotent stem cells that produce differentiating germ cells in the testis. (molcells.org)
  • These cells are commonly termed embryonic germ (EG) cells because they are derived from primordial germ cells found at the genital ridges in developing fetuses. (biomedcentral.com)
  • This paper outlines the debates prompted through a reproduction mechanism involv- by progress in cloning research, with special ing male and female germ cells. (who.int)
  • DAZ family proteins are found almost exclusively in germ cells in distant animal species. (ijbs.com)
  • Depending on the species, DAZL is expressed in primordial germ cells (PGCs) and/or pre-meiotic and meiotic germ cells of both sexes. (ijbs.com)
  • DAZ family proteins are located in the nucleus and/or in the cytoplasm of male and female germ cells at different developmental stages throughout the gametogenesis. (ijbs.com)
  • Dynamics of male canine germ cell development [6] "Primordial germ cells (PGCs) are precursors of gametes that can generate new individuals throughout life in both males and females. (edu.au)
  • To take human organ generation via BC and transplantation to the next step, we reviewed current emerging organ generation technologies and the associated efficiency of chimera formation in human cells from the standpoint of developmental biology. (frontiersin.org)
  • many are "totipotent" (as the abject fact of naturally occurring human identical twins makes clear). (lifeissues.net)
  • A minority of mouse embryonic stem cells (ESCs) display totipotent features resembling 2-cell stage embryos and are known as 2-cell-like (2C-like) cells. (bvsalud.org)
  • Up to the 2-cell embryo, blastomeres remain totipotent (Garner and McLaren, 1974). (conditionmed.org)
  • A fertilized egg is totipotent, meaning that its potential is total, and as the fertilized egg divides all the cells in the embryo remain totipotent until the fertilized egg has reached the 8/16-cell stage. (biomedcentral.com)
  • Approximately five days after fertilization the totipotent cells have differentiated and started to form a hollow sphere of cells called a blastocyst. (biomedcentral.com)
  • In the case of asexually creating a human, the biotechnologist removes the nucleus from a mature human egg (an oocyte). (cbc-network.org)
  • Generation of genetically modified mice by oocyte injection of androgenetic haploid embryonic stem cells. (nature.com)
  • Somatic cell cloning (cloning or nuclear transfer) is a technique in which the nucleus (DNA) of a somatic cell is transferred into an enucleated metaphase-II oocyte for the generation of a new individual, genetically identical to the somatic cell donor (Figure 1 ). (biomedcentral.com)
  • A matured oocyte (c) is then enucleated (d) and a donor cell is transferred into the enucleated oocyte (e). (biomedcentral.com)
  • Ethically, since eventually all such "research" will be applied to people, he cautions against the abuse of women "egg" donors, and against the premature use of vulnerable sick human patients for testing supposedly "patient-specific" stem cells in supposed "therapies", pointing to the obvious violations of standard international research ethics guidelines such clinical trials would necessarily entail. (lifeissues.net)
  • There are currently no controlled human clinical trials underway for ESC-derived therapies. (robertpgeorge.com)
  • With these new grants, California is continuing on the path of turning the hope and promise of stem cell research into the reality of therapies and cures for millions of Californians and people across the globe. (ca.gov)
  • The potential use of embryonic stem cells (ESCs) for cell replacement therapies is limited by ethical concerns and the technical hurdles associated with their isolation from human embryos. (biomedcentral.com)
  • We now see a patent landscape where stem cell technologies and related therapies can, with very few exceptions, be protected via patents, provided the appropriate form of claim wording is used. (schlich.co.uk)
  • This is junk biology since implanting isn't the act of asexual reproduction: SCNT cloning is. (cbc-network.org)
  • It is quite possible that the advances in human biology in the remainder of the twentieth century will be remembered as the most significant scientific achievement of the animal species known as Homo sapiens . (lifeissues.net)
  • The real experts to ask about the accurate scientific facts of human embryology are the scientific experts in human embryology who are academically credentialed Ph.D. human embryologists - not the "experts" in cell biology, genetics, doctors, nurses, theologians, lawyers or politicians, secretaries, news journalists, etc. (lifeissues.net)
  • We were the first to link Wnt signaling with adult stem cell biology, when we showed that TCF4 gene disruption leads to the abolition of crypts of the small intestine (8), and that TCF1 gene knockout severely disables the stem cell compartment of the thymus (2). (hubrecht.eu)
  • Understanding cell-fate decisions in stem cell populations is a major goal of modern biology. (lu.se)
  • One of the greatest controversies triggered tissue, a stem cell encoding for heart tissue by the rapid pace of evolution in biology, will eventually develop into heart tissue particularly in genomics and biotechnology, and so on. (who.int)
  • The signatories include human-biology research scientists, obstetricians, gynaecologists, professors of a range of disciplines, doctors in general practice and nurses. (blogspot.com)
  • There has been one previous report showing that overexpression of Sirt6 in aged human dermal fibroblasts could improve iPS generation via regulation of miR-766 transcription [ 19 ]. (biomedcentral.com)
  • 2008). Historically, this concept is highlighted by the experi- factors are key intrinsic regulators of these fate decisions and mental phenomenon of lineage reprogramming, for example, that fate choice involves modulating networks of transcription by the conversion of fibroblasts to muscles cells following trans- factors. (lu.se)
  • In cultured primary fibroblasts and cancer cells, the chemotherapeutic drug doxorubicin causes mtDNA damage and release, which leads to cGAS STING dependent ISG activation. (regenerativemedicine.net)
  • But in order to become a part of medical history, parahuman reproduction and human genetic engineering must circumvent the recalcitrance of an antiquated culture. (lifeissues.net)
  • In the real world, there is no such thing scientifically as a "pre-embryo", or "just a genetic individual" as opposed to a "developmental individual. (lifeissues.net)
  • Wutz, A. Haploid mouse embryonic stem cells: rapid genetic screening and germline transmission. (nature.com)
  • Genetic modification and screening in rat using haploid embryonic stem cells. (nature.com)
  • How may genetic information associated with the cell line be accessed? (hpscreg.eu)
  • In addition to these basic issues concerning leukemia pathogenesis, we are devising new diagnostic procedures for detecting and monitoring leukemia patients based on molecular genetic abnormalities in the malignant cells. (stanford.edu)
  • The lab focuses on multifaceted regulation by transcription and epigenetic factors, lncRNAs, membraneless organelles, mechanisms of self-renewal, and extensively uses organoid technology, single cell RNA sequencing, flow cytometry, and CRISPR-Cas9 genetic engineering approaches. (universiteitleiden.nl)
  • Stem cells have been used to repair tissue damaged by disease. (wikipedia.org)
  • The primary legislation in South Africa that deals with embryo research is the Human Tissue Act, which is set to be replaced by Chapter 8 of the National Health Act. (wikipedia.org)
  • Induced pluripotent stem cells, another types of pluripotent stem cells derived from any tissue by reprogramming and are the homologous source of stem cells. (benthamscience.com)
  • XI - embryonic stem cells: embryonic cells that are capable of modifying the cells of any organism tissue. (hinxtongroup.org)
  • The Organoid group, previously Clevers group, studies the molecular mechanisms of tissue development and cancer of various organs using organoids made from adult Lgr5 stem cells. (hubrecht.eu)
  • These cells represent the epithelial stem cells of the small intestine and colon (23), the hair follicle (24), the stomach (28) and many other tissue stem cell types. (hubrecht.eu)
  • Has informed consent been obtained from the donor of the embryo/tissue from which the pluripotent stem cells have been derived? (hpscreg.eu)
  • Does the consent permit uses of donated embryo/tissue or derived cell line intended for clinical treatment or human applications? (hpscreg.eu)
  • Does consent expressly prevent financial gain from any use of the donated embryo/tissue, including any product made from it? (hpscreg.eu)
  • Does consent expressly permit storage of donated embryo/tissue for an unlimited time? (hpscreg.eu)
  • Has the donor consented to receive information discovered during use of donated embryo/tissue that has significant health implications for the donor? (hpscreg.eu)
  • We have previously shown that human kidney tissue can be generated from human pluripotent stem cells. (atlas-d2k.org)
  • In the long term, human kidney tissue generated in this way may be used for drug screening, tissue regeneration or cell therapy. (atlas-d2k.org)
  • International bi-monthly journal of cell signaling, tissue protection, and translational research. (conditionmed.org)
  • The blastocyst comprises the inner cell mass (ICM), which gives rise to the three primary germ layers and consequently the fetus, and the trophectoderm (TE), which gives rise to the extraembryonic and placental tissue. (conditionmed.org)
  • ZO-2 and ZO-3 are ubiquitously expressed within epithelial tight junctions, and unlike ZO-1, which is also expressed at cell junctions of cardiac myocytes, ZO-2 is not expressed in nonepithelial tissue. (thermofisher.com)
  • In 2001, the British Parliament amended the Human Fertilisation and Embryology Act 1990 (since amended by the Human Fertilisation and Embryology Act 2008) to permit the destruction of embryos for hESC harvests but only if the research satisfies one of the following requirements: Increases knowledge about the development of embryos, Increases knowledge about serious disease, or Enables any such knowledge to be applied in developing treatments for serious disease. (wikipedia.org)
  • … "embryo" means a human organism during the first 56 days of its development following fertilization or creation, excluding any time during which its development has been suspended, and includes any cell derived from such an organism that is used for the purpose of creating a human being. (hinxtongroup.org)
  • increased public sensitivity and awareness together with the development of national regulations of governance of human cloning and embryo research in general. (lifeissues.net)
  • The ability to study human post-implantation development remains limited owing to ethical and technical challenges associated with intrauterine development after implantation 1 . (nature.com)
  • This SEM platform will probably enable the experimental investigation of previously inaccessible windows of human early post implantation up to peri-gastrulation development. (nature.com)
  • Implantation of the human embryo leads to a number of changes in organization that are essential for gastrulation and future development 1 . (nature.com)
  • Development of new ways of deriving hESCs and investigating the special capabilities of newly-derived human cell lines. (ca.gov)
  • Recording and contextualizing the science of embryos, development, and reproduction. (asu.edu)
  • These data provide insight into epigenetic errors that may be associated with the poor development of embryos generated from immature spermatozoa. (shengsci.com)
  • In studies initially focused on roles of nonmuscle myosin IIA (NMIIA) in the developing mouse epidermis, we have discovered that a previously described cytokeratin 5 (K5)-Cre gene construct is expressed in early embryo development. (shengsci.com)
  • Revealing cell populations catching the early stages of the human embryo development in naïve pluripotent stem cells. (axonmedchem.com)
  • The study of the new dab2 mutant allele in embryos and embryoid bodies confirms a role for Dab2 in extraembryonic endoderm development and epithelial organization. (biomedcentral.com)
  • Conditional deletion indicates that Dab2 is dispensable for organ development, when the vast majority of the embryonic cells are dab2 null. (biomedcentral.com)
  • Functional analysis further demonstrated that hES lincRNAs were preferentially involved in multiple development processes including embryo development, ribosome biogenesis, and aging. (biomedcentral.com)
  • BACKGROUND: During normal human kidney development, nephrogenesis (the formation of nephrons) is complete by term birth, with the majority of nephrons formed late in gestation. (atlas-d2k.org)
  • The revised ontology will be an important tool for researchers studying urogenital development/malformation in mouse models and will improve our capacity to appropriately interpret these with respect to the human situation. (atlas-d2k.org)
  • We are studying the role that normal chromatin structure plays in gene regulation in hematopoietic cells and how its disruption leads to altered development and cancer. (stanford.edu)
  • Here, we consider the metabolism of the early embryo through development, and look at the nutrient milieu within the developing stem cell niche. (conditionmed.org)
  • 2020). This places metabolism at the forefront of development and cell state decisions. (conditionmed.org)
  • The developing embryo, from which pluripotent stem cells originate, undergoes a series of dynamic metabolic transitions synchronized to its molecular development. (conditionmed.org)
  • There are different types of stem cells that best can be described in the context of normal human development [ 23 ]. (biomedcentral.com)
  • Following cumulus removal, 2i accelerated blastocyst development and increased inner cell mass (ICM) and trophoblast cell numbers by 30% and 27%, respectively. (bioone.org)
  • Many of these developmental abnormalities are common to human development. (edu.au)
  • Keratin 5-Cre-driven excision of nonmuscle myosin IIA in early embryo trophectoderm leads to placenta defects and embryonic lethality. (shengsci.com)
  • Stem cell laws are the law rules, and policy governance concerning the sources, research, and uses in treatment of stem cells in humans. (wikipedia.org)
  • The European Union has yet to issue consistent regulations with respect to stem cell research in member states. (wikipedia.org)
  • Whereas Germany, Austria, Italy, Finland, Portugal and the Netherlands prohibit or severely restrict the use of embryonic stem cells, Greece, Sweden, Spain and the United Kingdom have created the legal basis to support this research. (wikipedia.org)
  • Germany has restrictive policies for stem cell research, but a 2008 law authorizes "the use of imported stem cell lines produced before May 1, 2007. (wikipedia.org)
  • According to modern stem cell researchers, Spain is one of the leaders in stem cell research and currently has one of the most progressive legislations worldwide with respect to human embryonic stem cell (hESC) research. (wikipedia.org)
  • The new Spanish law allows existing frozen embryos - of which there are estimated to be tens of thousands in Spain - to be kept for patient's future use, donated for another infertile couple, or used in research. (wikipedia.org)
  • In 2003, Spain's laws state that embryos left over from IVF and donated by the couple that created them can be used in research, including ES cell research, if they have been frozen for more than five years. (wikipedia.org)
  • The United Kingdom is one of the leaders in stem cell research, in the opinion of Lord Sainsbury, Science and Innovation Minister for the UK. (wikipedia.org)
  • A new £10 million stem cell research centre has been announced at the University of Cambridge. (wikipedia.org)
  • The bill purports to promote stem-cell research, while outlawing the cloning of a human being. (cbc-network.org)
  • While stem-cell research holds enormous potential for treating or even curing some diseases, the cloning of a human being is morally and ethically unacceptable…Any attempt to clone a human being is in direct conflict with the public policies of this state. (cbc-network.org)
  • But they are also less equipped to produce every cell type of the body and less able to reproduce themselves indefinitely, which makes them less appealing to scientists interested in basic research. (eppc.org)
  • These moral perils are surely not a reason to oppose adult stem cell research, which deserves vigorous and expanded public support. (eppc.org)
  • Since 1995, Congress has annually reauthorized a law-called the "Dickey Amendment"-prohibiting federal funding for research "in which" embryos are destroyed while leaving embryo destruction in the private sector entirely unregulated. (eppc.org)
  • Before leaving office, President Clinton sought to get around the existing law without actually changing it, by funding research on embryonic stem cells so long as the actual embryo destruction was paid for with private dollars. (eppc.org)
  • The recent desperation to clone human embryos may be seriously undermining accepted ethical principles of medical research, with potentially profound wider consequences. (lifeissues.net)
  • And he also agrees that if we don't find global agreement on human cloning, "we can probably expect dire consequences for the future of biomedical research and its impact on society at large. (lifeissues.net)
  • As he has questioned the HFEA before, would not the use of vulnerable human patients in clinical trials be premature, dangerous, and unethical given the already acquired knowledge in the research community that such supposed "patient-specific" stem cells would most probably cause serious immune rejection reactions in these patients? (lifeissues.net)
  • Americans are divided over the question of whether it is morally acceptable to authorize by law, and fund with taxpayer dollars, research in which human embryos are destroyed. (robertpgeorge.com)
  • Stating that such research "crosses a moral boundary that our decent society needs to respect," President Bush vetoed legislation last summer that would have expanded federal funding of human embryonic stem cell (ESC) research. (robertpgeorge.com)
  • There is no "ban" on human embryonic stem cell research in the United States. (robertpgeorge.com)
  • Out of all peer-reviewed research papers published from 1998 through 2005 on original human ESC research, scientists from the U.S. published by far the most, 125 of the 315. (robertpgeorge.com)
  • The committee was willing to support the use of "excess" embryos from assisted reproduction clinics, but only if their use was necessary to advance life-saving research. (robertpgeorge.com)
  • It did not endorse the creation of embryos by cloning or other methods for use in research involving their destruction. (robertpgeorge.com)
  • It is increasingly clear that there are non-embryo destructive research alternatives that hold out the promise of providing sources of stem cells with properties equivalent to, or nearly equivalent to, embryonic cells. (robertpgeorge.com)
  • You don't need religion to tremble at the thought of unrestricted embryo research. (robertpgeorge.com)
  • An in-depth analysis aiming at re-defining this terminology according to the new developments in human embryo research would be highly beneficial . (lifeissues.net)
  • Stem cell research has the potential to provide treatments for a host of debilitating diseases including Alzheimer's, Parkinson's, diabetes, multiple sclerosis, heart disease, and spinal cord injury. (gc.ca)
  • In recognition of this and because of the complex ethical issues that it raises, the President of CIHR convened the Ad Hoc Working Group on Stem Cell Research in the fall of 2000. (gc.ca)
  • Its mandate was to advise CIHR as to whether human embryonic stem cell and human embryonic germ cell research should be considered eligible for CIHR funding. (gc.ca)
  • While research on human adult stem cells was not included in the Working Group's mandate, recent scientific research has confirmed the possibility of generating human pluripotent stem cells with properties similar to embryonic stem cells from adult cells (e.g., induced pluripotent stem cells). (gc.ca)
  • In January 2002, after a year of discussion and consultation, the group produced a report to CIHR's Governing Council, which was unanimously accepted and formed the basis of human pluripotent stem cell research guidelines that were publicly announced in March 2002. (gc.ca)
  • Until then, Canada had no laws to govern human pluripotent stem cell research, nor were there any guidelines for researchers, research ethics boards, or funding agencies on how human pluripotent stem cells may be derived and used. (gc.ca)
  • The guidelines provided for the review of human stem cell research applications by a Stem Cell Oversight Committee (SCOC). (gc.ca)
  • In March 2004, an Act Respecting Assisted Human Reproduction and Related Research , became law. (gc.ca)
  • The Act applies to the derivation of human pluripotent stem cells from human embryos, but does not apply to research using human embryonic stem cell lines that have already been derived. (gc.ca)
  • In 2014, the guidelines were integrated into the 2nd Edition of the Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans (TCPS 2) . (gc.ca)
  • The former CIHR Guidelines for Human Pluripotent Stem Cell Research (2002, 2005, 2006, 2007, and 2010), the Report of the ad hoc working group (2002) and Discussion paper (2001) are available in electronic format on request. (gc.ca)
  • LOS ANGELES, March 16, 2007 - Just a month after approving nearly $45 million for embryonic stem cell research, California's stem cell agency authorized another $75.7 million in additional funds for established scientists at 12 non-profit and academic institutions. (ca.gov)
  • The California spirit - the perseverance, creativity and resourcefulness that has made us a leader on everything from gold mining in the 19th Century to fighting global warming in this one - is fully present in our stem cell research teams. (ca.gov)
  • As of today, California is the largest and most stable source of funding for human embryonic stem cell research in the world," Klein said. (ca.gov)
  • These grants provide substantial support to a pool of very distinguished researchers in human embryonic stem cell research," declared Zach W. Hall, Ph.D., CIRM's President and Chief Scientific Officer. (ca.gov)
  • Combined with our training and SEED grants, the CIRM is now funding embryonic stem cell research in more than 100 California laboratories. (ca.gov)
  • We focused our initial grants on human embryonic stem cells specifically," Klein said, "because human embryonic stem cell research receives minimal funding from the federal government, and even those funds are restricted to lines of questionable value. (ca.gov)
  • Going forward, we will support a diverse range of stem cell research projects. (ca.gov)
  • Since the discovery of induced pluripotent stem (iPS) cells, the molecular mechanism underlying the reprogramming process has been an active area of research. (biomedcentral.com)
  • Developmental defects, including abnormalities in cloned fetuses and placentas, in addition to high rates of pregnancy loss and neonatal death have been encountered by every research team studying somatic cloning. (biomedcentral.com)
  • Does the consent anticipate that the donor will be notified of results or outcomes of any research involving the donated samples or derived cells? (hpscreg.eu)
  • Stem cells and organoids Hans Clevers became famous with his stem-cell research into healthy and sick intestines. (maquisadeoccidente.com)
  • Chief among these are the legalisation of abortion and approval for research that harms or destroys human embryos. (blogspot.com)
  • Nor do only the cells of the inner cell mass of the blastocyst become the later adult and none of the cells from the inner cell mass become part of the placenta, umbilical cord, etc. (lifeissues.net)
  • Multipotent stem cells are present in the adult individual as well as the fetus and umbilical cord. (biomedcentral.com)
  • The second way to reproduce is a strictly human invention - known as "asexual" reproduction - or more commonly, cloning. (cbc-network.org)
  • Cloning of a human being" means asexual reproduction by implanting or attempting to implant the product of nuclear transplantation [e.g., an embryo] into a uterus or substitute for a uterus with the purpose of producing a human being. (cbc-network.org)
  • your supposed cloning ban actually authorizes human cloning, implantation, and gestation through the ninth month. (cbc-network.org)
  • That is what New Jersey legislators did when they passed and then Governor James McGreevey signed S-1909 last year, a law that was sold to the public as outlawing human cloning but which actually permits the creation of cloned human life, and its implantation and gestation up to and including the very moment prior to the emergence of the cloned baby from the birth canal. (cbc-network.org)
  • Or to put it the other way around, cloning, not implantation, is what produces a new and distinct human organism. (cbc-network.org)
  • Nor is the embryo just a "fertilized egg", or just a "clump of cells", or appear only when the zygote is formed, or appear later after the zygote is formed, or appear after implantation - or even a week after that at 14-days. (lifeissues.net)
  • Such human fully integrated and complete SEMs recapitulate the organization of nearly all known lineages and compartments of post-implantation human embryos, including the epiblast, the hypoblast, the extra-embryonic mesoderm and the trophoblast layer surrounding the latter compartments. (nature.com)
  • These human complete SEMs demonstrated developmental growth dynamics that resemble key hallmarks of post-implantation stage embryogenesis up to 13-14 days after fertilization (Carnegie stage 6a). (nature.com)
  • and (3) evidence of developmental dynamism relating to ability to progress, in a structurally organized manner, through morphologically characterized developmental milestones of the early post-implantation human embryo following initial aggregate formation 3 . (nature.com)
  • Cells derived from the BLASTOCYST INNER CELL MASS which forms before implantation in the uterine wall. (edu.au)
  • And now Washington joins the infamous list with Senate Bill 5594, a thoroughly disingenuous piece of legislation that purports to outlaw the cloning of human beings, but by manipulating language and redefining terms, actually permits human cloning and gestation of the resulting cloned embryos through the ninth month. (cbc-network.org)
  • The blastocyst can then be transferred to a recipient (h) and cloned animals are born after completion of gestation (i). (biomedcentral.com)
  • The proportions of podocytes, endothelial and non-epithelial cells within mature glomeruli were stable throughout gestation. (atlas-d2k.org)
  • In January 2007, researchers at Wake Forest University reported that "stem cells drawn from amniotic fluid donated by pregnant women hold much of the same promise as embryonic stem cells. (wikipedia.org)
  • However, the derivation of human NT-ESCs goes with the destruction of clone embryos, leading to fierce ethical disputes. (benthamscience.com)
  • That is to say, we risk turning developed cells into developing embryos, and thus risk engaging in the very activities of embryo destruction and human cloning that we seek to avoid. (eppc.org)
  • Concerns about embryo destruction are not only religious. (robertpgeorge.com)
  • 1995) and subsequently in primary cells (Heyworth et al. (lu.se)
  • In this regard, emerging technologies of chimeric human organ production via blastocyst complementation (BC) holds great promise. (frontiersin.org)
  • In the mouse, a transporting epithelium is established around the 8-16-cell stage through a process known as compaction where cell definition is lost and the outer cells of the embryo form tight junctions, giving rise to the blastocyst. (conditionmed.org)
  • Compared to vehicle controls, 2i conditions increased the abundance of cumulus cells in bovine IVF cultures, which compromised blastocyst formation. (bioone.org)
  • The primary cloning technique is called "somatic cell nuclear transfer" (SCNT). (cbc-network.org)
  • If the authors of this bill really meant what they appear to have written, their legislation would ban all human cloning, since as we have seen, biologically, a new human organism, that is, a new human being, comes into existence with the completion of SCNT. (cbc-network.org)
  • What is more, by deriving NT-ESCs from patient cells, the problem of immune rejection may be avoided. (benthamscience.com)
  • Here, we report that the overexpression of negative elongation factor A (Nelfa), a maternally provided factor, enhances the conversion of ESCs into 2C-like cells in chemically defined conditions, while the deletion of endogenous Nelfa does not block this transition. (bvsalud.org)
  • Interestingly, we found that the co-overexpression of Nelfa and Bcl2 robustly activates the 2C-like state in ESCs and endows the cells with dual cell fate potential. (bvsalud.org)
  • The Act also prohibits certain activities such as cloning humans or creating chimeras. (gc.ca)
  • The non-embryonic stem cells like adult stem cells are in clinical use for many years and embryonic stem cells are now emerging as an alternative source for the same purpose with huge potentials in drug discovery and toxicological studies. (benthamscience.com)
  • By contrast, there are currently some 1200 clinical trials underway associated with human adult stem cells (ASCs). (robertpgeorge.com)
  • The biological properties and clinical potential of stem cells elicit that are generated must not be unduly sensitive to small fluctu- continued scientific, commercial, and public interest. (lu.se)
  • The Tcf4-driven target gene program in colorectal cancer cells is the malignant counterpart of a physiological gene program in selfrenewing crypts (13, 14). (hubrecht.eu)
  • Amongst the intestinal Wnt target genes (13), we found the Gpr49/Lgr5 gene to be unique in that it marks small cycling cells at crypt bottoms. (hubrecht.eu)
  • The Wnt target gene encoding the transcription factor Achaete scute-like 2 controls intestinal stem cell state (26). (hubrecht.eu)
  • Similarly, GATA-1 has been shown to induce lineage switching expression values even if, for simplicity, we assume only ``on'' of committed cells in hematopoiesis, first in cell lines (Kulessa and ``off'' states for each gene. (lu.se)
  • In reality, gene somatic cells to a pluripotent cell state by a handful of transcrip- expression is graded, making the potential gene expression tion factors (Takahashi and Yamanaka, 2006). (lu.se)
  • A fragment of the Dab2 human cDNA was also isolated based on its frequent loss of expression in ovarian cancer, and was termed DOC-2 (Differentially expressed in ovarian carcinoma gene 2) [ 2 ]. (biomedcentral.com)
  • Deletion of DAZ gene is the most common causes of infertility in humans. (ijbs.com)
  • To varying degrees, these fates also extend to the Such state stability is required in stem and progenitor cells to immediate progeny of stem cells, known as progenitor or support self-renewal and maintenance of the uncommitted transit-amplifying cells. (lu.se)
  • Progenitor cells from which all blood cells derived. (edu.au)
  • These developmental defects have been attributed to incomplete reprogramming of the somatic nuclei by the cloning process. (biomedcentral.com)
  • Ontology changes were based on recently published insights into the cellular and gross anatomy of these structures, and on new analyses of epithelial cell types present in the pelvic urethra and regions of the bladder. (atlas-d2k.org)
  • Although it is possible to culture structures derived from human blastocysts ex vivo, these cultures do not recapitulate the events and structural organization of the in vivo embryos 6 ( Supplementary Information ). (nature.com)
  • Modulation of LDL receptor endocytosis by Dab2 has also been studied in cultured cells [ 36 ], though a role in vivo has not yet been established. (biomedcentral.com)
  • In addition, mtDNA stress in TFAM-deficient mouse melanoma cells produces tumours that are more resistant to doxorubicin in vivo. (regenerativemedicine.net)
  • There are now two ways to create new mammalian life, including humans. (cbc-network.org)
  • Cloning by nuclear transfer using mammalian somatic cells has enormous potential application. (biomedcentral.com)
  • Growing self-organizing mini-guts from a single intestinal stem cell: mechanism and applications. (maquisadeoccidente.com)
  • Furthermore, the functionality of feeder-free cultured SSCs was confirmed by their transplantation into germ cell-depleted mice. (molcells.org)
  • in 1956 and Till and McCulloch in 1961, demonstrating that lethally irradiated mice could be rescued with cells from freshly isolated bone marrow [ 10 ] and that BM cells formed spleen clonies (CFU-S) following transplantation to irradiated recipients [ 30 ], respectively. (biomedcentral.com)
  • Stem cell treatments are a type of cell therapy that introduce new cells into adult bodies for possible treatment of cancer, somatic cell nuclear transfer, diabetes, and other medical conditions. (wikipedia.org)
  • Although exciting results have been achieved by means of somatic cell nuclear transfer, cell fusion, and culture-induced reprogramming [ 1 ], these procedures are technically demanding and inefficient and therefore unlikely to become a common approach for producing patient-specific pluripotent cells. (biomedcentral.com)
  • Because cattle are a species widely used for nuclear transfer studies, and more laboratories have succeeded in cloning cattle than any other specie, this review will be focused on somatic cell cloning of cattle. (biomedcentral.com)
  • Currently, the efficiency for nuclear transfer is between 0-10%, i.e., 0-10 live births after transfer of 100 cloned embryos. (biomedcentral.com)
  • Various strategies have been employed to modify donor cells and the nuclear transfer procedure in attempts to improve the efficiency of nuclear transfer. (biomedcentral.com)
  • Although the efficiency of nuclear transfer has been dramatically improved from the initial success rate of one live clone born from 277 embryo transfers [ 1 ], none of the aforementioned efforts abolished the common problems associated with nuclear transfer. (biomedcentral.com)
  • These include embryonic disc and bilaminar disc formation, epiblast lumenogenesis, polarized amniogenesis, anterior-posterior symmetry breaking, primordial germ-cell specification, polarized yolk sac with visceral and parietal endoderm formation, extra-embryonic mesoderm expansion that defines a chorionic cavity and a connecting stalk, and a trophoblast-surrounding compartment demonstrating syncytium and lacunae formation. (nature.com)
  • The genetically modified egg now has 46 chromosomes, the full human compliment. (cbc-network.org)
  • Here we extend those findings to humans using only genetically unmodified human naive embryonic stem cells (cultured in human enhanced naive stem cell medium conditions) 4 . (nature.com)
  • James Thomson, the first scientist to derive stem cells from a human embryo, made this point clearly just a few weeks ago: "I don't want to sound too pessimistic because this is all doable, but it's going to be very hard. (robertpgeorge.com)
  • To circumvent these obstacles, considerable effort has been invested in attempting to derive ESC-like cells by reprogramming somatic cells to an embryonic state. (biomedcentral.com)
  • In July 2005, for example, scientists announced that they had engineered adult mouse stem cells into usable mouse eggs, a technique that might one day allow for the creation of human eggs from ordinary human cells. (eppc.org)
  • Mouse naive embryonic stem cells have recently been shown to give rise to embryonic and extra-embryonic stem cells capable of self-assembling into post-gastrulation structured stem-cell-based embryo models with spatially organized morphogenesis (called SEMs) 3 . (nature.com)
  • Leeb, M. & Wutz, A. Derivation of haploid embryonic stem cells from mouse embryos. (nature.com)
  • Forward and reverse genetics through derivation of haploid mouse embryonic stem cells. (nature.com)
  • Based on these combined insights, we have established Lgr5/R-spondin-based culture systems that allow the outgrowth of single mouse or human Lgr5 stem cells into ever-expanding organoids. (hubrecht.eu)
  • However, human anatomical terms do not always superimpose on the mouse, and the lack of accurate and standardised nomenclature is hampering the utility of such animal models. (atlas-d2k.org)
  • The nucleus of a body cell from the DNA donor is removed, and put into the place formerly occupied by the egg's nucleus. (cbc-network.org)
  • However, though BC is emerging as a potential organ transplant option, challenges regarding organ size scalability, immune system incompatibilities, long-term maintenance, potential evolutionary distance, or unveiled mechanisms between donor and host cells remain. (frontiersin.org)
  • Most of these efforts are focused on donor cells. (biomedcentral.com)
  • Has the donor been informed that their donated biosample or derived cells may be tested for the presence of microbiological agents / pathogens? (hpscreg.eu)
  • We explore the recently described metabolic surge event that occurs as pluripotency is lost and stem cells commit to differentiate. (conditionmed.org)
  • Until recently it was considered a fact that, for example, hematopoietic stem cells did not have the potential to differentiate into cells of other types than the cells constituting the blood system. (biomedcentral.com)
  • The have been applied to both the plant and ani- stem cells possess pluripotential charac- mal kingdoms without even stirring a ripple teristics, and can differentiate into various of concern in international conscience [ 2 ]. (who.int)