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Results for “Multipotent Stem Cells”

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At least 361 records · Page 20Linked to original sources

PubMed2007

Simultaneous generation of CD34+ primitive hematopoietic cells and CD73+ mesenchymal stem cells from human embryonic stem cells cocultured with murine OP9 stromal cells.

OBJECTIVE: Human embryonic stem cells (hESCs) have been shown to generate CD34(+) primitive hematopoietic cells after several days of coculturing with the OP9 murine stromal cell line. CD73(+) multipotent mesenchymal cells have also been isolated from hESC/OP9 cocultures after several weeks. We hypothesized that generation of CD34(+) hematopoietic cells and CD73(+) mesenchymal stem cells (MSCs) may follow similar kinetics, so we investigated the generation of CD73(+) cells in the first 2 weeks of hESC/OP9 cocultures, at a time when CD34(+) cells are generated. MATERIALS AND METHODS: We cocultured hESCs with OP9 cells and examined the time course of appearance of human CD34(+) and CD73(+) cells using flow cytometry. We tested the hematopoietic progenitor potentials of CD34(+) cells generated using hematopoietic colony-forming assays, and the multipotent mesenchymal properties of CD73(+) cells generated using in vitro differentiation assays. RESULTS: We observed that in the first 2 weeks of the hESC/OP9 coculture system CD34(+) hematopoietic and CD73(+) MSC generation follows a similar pattern. We sorted the CD34(+) cells and showed that they can generate hematopoietic progenitor colonies. Starting with cocultured cells on day 8, and through an enrichment procedure, we also could generate a pure population of MSCs. These hESC-derived MSCs had typical morphological and cell surface marker characteristics of adult bone marrow-derived MSCs, and could be differentiated toward osteogenic, adipogenic, and chondrogenic cells in vitro, a hallmark property of MSCs. CONCLUSIONS: OP9 cells when cocultured with hESCs support simultaneous generation of CD34(+) primitive hematopoietic cells and CD73(+) MSCs from hESCs.

5'-Nucleotidase↗

PubMed2005

A tumorigenic subpopulation with stem cell properties in melanomas.

Recent studies suggest that cancer can arise from a cancer stem cell (CSC), a tumor-initiating cell that has properties similar to those of stem cells. CSCs have been identified in several malignancies, including those of blood, brain, and breast. Here, we test whether stem cell-like populations exist in human melanomas. In approximately 20% of the metastatic melanomas cultured in growth medium suitable for human embryonic stem cells, we found a subpopulation of cells propagating as nonadherent spheres, whereas in standard medium, adherent monolayer cultures were established. Individual cells from melanoma spheres (melanoma spheroid cells) could differentiate under appropriate conditions into multiple cell lineages, such as melanocytic, adipocytic, osteocytic, and chondrocytic lineages, which recapitulates the plasticity of neural crest stem cells. Multipotent melanoma spheroid cells persisted after serial cloning in vitro and transplantation in vivo, indicating their ability to self-renew. Furthermore, they were more tumorigenic than adherent cells when grafted to mice. We identified similar multipotent spheroid cells in melanoma cell lines and found that the stem cell population was enriched in a CD20+ fraction of melanoma cells. Based on these findings, we propose that melanomas can contain a subpopulation of stem cells that contribute to heterogeneity and tumorigenesis. Targeting this population may lead to effective treatments for melanomas.

Animals↗

PubMed2003

Are adult cardiocytes still able to proliferate?

In all mammals including humans, adult cardiocytes become post mitotic cells, while cardiac non muscle cells still have the capacity to proliferate, and cardiac hypertrophy in adults is known to be due to cardiocyte hypertrophy and non muscle cell hyperplasia. Such a dogma was supported by several, rather ancient, observations, and has been recently challenged by two different groups. Several new paradigms in cell biology have modified these views: the entire determinants of the cell cycle are now entirely known; apoptosis, and cardiac apoptosis, is central in the process of cell division, and has a rather complicated significance; telomeres are specialized DNA-protein structures that prevent end-to-end chromosome fusion, and are rather characteristic of germ and stem cells, these structures are maintained by telomerase. Using several markers, including telomerase activity, endogenous self-renewing, clonogenic and multipotent stem cells were identified in the adult myocardium in human, mice and rat. These cells are activated during cardiac overload or ischemia to produce new cardiocytes. New endothelial cells also appeared, and are likely to have a circulatory origin. The physiological importance of these new cells is debatable at the moment. Nevertheless, these findings provide an important new basis for cell cardiomyoplasty. It is also possible to envisage stimulation of the production and activity of these new cells to compensate for the lack of substance after myocardial infarction.

Animals↗

PubMed1999

Identification of a neural stem cell in the adult mammalian central nervous system.

New neurons are continuously added in specific regions of the adult mammalian central nervous system. These neurons are derived from multipotent stem cells whose identity has been enigmatic. In this work, we present evidence that ependymal cells are neural stem cells. Ependymal cells give rise to a rapidly proliferating cell type that generates neurons that migrate to the olfactory bulb. In response to spinal cord injury, ependymal cell proliferation increases dramatically to generate migratory cells that differentiate to astrocytes and participate in scar formation. These data demonstrate that ependymal cells are neural stem cells and identify a novel process in the response to central nervous system injury.

Animals↗

PubMed2005

Isolation of two human fibroblastic cell populations with multiple but distinct potential of mesenchymal differentiation by ceiling culture of mature fat cells from subcutaneous adipose tissue.

Adipose tissue is a source of adult multipotent stem cells that can differentiate along mesenchymal lineage. When mature fat cells obtained from human subcutaneous adipose tissue were maintained with attachment to the ceiling surface of culture flasks filled with medium, two fibroblastic cell populations appeared at the ceiling and the bottom surface. Both populations were positive to CD13, CD90, and CD105, moderately positive to CD9, CD166, and CD54, negative to CD31. CD34, CD66b, CD106, and CD117, exhibited potential of unlimited proliferation, and differentiated along mesenchymal lineage to produce adipocytes, osteoblasts, and chondrocytes. The population that appeared at the ceiling surface showed higher potential of adipogenic differentiation. These observations showed that the cells tightly attached to mature fat cells can generate two fibroblastic cell populations with multiple but distinct potential of differentiation. Since enough number of both populations for clinical transplantation can be easily obtained by maintaining fat cells from a small amount of subcutaneous adipose tissue, this method has an advantage in preparing autologous cells for patients needing repair of damaged tissues by reconstructive therapy.

Adipose Tissue↗

PubMed1998

Stem cells in the embryonic cerebral cortex: their role in histogenesis and patterning.

The cytoarchitectural simplicity of the cerebral cortex makes it an attractive system to study central nervous system (CNS) histogenesis--the process whereby diverse cells are generated in the right numbers at the appropriate place and time. Recently, multipotent stem cells have been implicated in this process, as progenitor cells for diverse types of cortical neurons and glia. Continuous analysis of stem cell clone development reveals stereotyped division patterns within their lineage trees, highly reminiscent of neural lineage trees in arthropods and Caenorhabditis elegans. Given that these division patterns play a critical part in generating diverse neural types in invertebrates, we speculate that they play a similar role in the cortex. Because stereotyped lineage trees can be observed from cells growing at clonal density, cell-intrinsic factors are likely to have a key role in stem cell behavior. Cortical stem cells also respond to environmental signals to alter the types of cells they generate, providing the means for feedback regulation on the germinal zone. Evidence is accumulating that cortical stem cells, influenced by intrinsic programs and environmental signals, actually change with development-for example, by reducing the number and types of neurons they produce. Age-related changes in the stem cell population may have a critical role in orchestrating development; whether these cells truly self-renew is a point of discussion. In summary, we propose that cortical stem cells are the focus of regulatory mechanisms central to the development of the cortical cytoarchitecture.

Animals↗

PubMed2003

Self-renewal and differentiation of hematopoietic stem cells: a molecular approach (a review).

Two characteristics define a hematopoietic stem cell: the ability to differentiate into all hematopoietic lineages, and the ability to maintain hematopoiesis over a life span by a self-renewal process. The mechanisms that regulate the fate of blood-forming cells in vivo, however, are poorly understood. Despite the ability to culture hematopoietic progenitor cells (committed to particular lineages), in vitro culture of self-renewing multipotent stem cells has not yet been achieved. What is clear that both intrinsic and extrinsic signals regulate hematopoietic stem cell fate and some of these signals have now been identified. which will be highlighted in this review.

Animals↗

PubMed2004

Prognosis in childhood and adult acute lymphoblastic leukaemia: a question of maturation?

Acute lymphoblastic leukaemia (ALL) is a disease diagnosed in children as well as adults. Progress in the treatment of ALL has led to better survival rates, however, children have benefited more from improved treatment modalities than adults. Recent evidence has underscored that the difference in characteristics and biology of adult versus childhood ALL might be the result of a different origin. According to the two-hit paradigm of Knudson, to develop cancer two genetic events are necessary. It has been suggested, that in childhood ALL the first genetic event happens in the more mature lymphoid committed progenitor cells, whereas in adult ALL the first hit occurs in multipotent stem cells. This review compares patient characteristics, the extent of the disease, leukaemic cell characteristics and treatment between childhood and adult ALL. This is discussed in relation to the hypothesis that the maturation stage of the cells, from which the leukaemia arises, is responsible for the differential behaviour of adult and childhood ALL.

Adolescent↗

PubMed2006

Basic science for the clinician 38: B cells, factories, and immunomodulators.

In a previous article in this series, we explored how developing pre-T cells learn how to be well-behaved T cells that recognize and honor the "self versus nonself" dichotomy of the universe. B cells do much of the same sort of thing, with multipotent stem cells becoming committed to ultimately becoming B cells within the bone marrow and then, after judicious culling of the flock, going off to the spleen to learn the final lessons needed to become "well-behaved" B cells. Like with T cells, there are a large number of things that can, and do, go wrong. If there is a failure of the system and B cells do not develop properly, hypogammaglobulinemia may develop as a result of a number of immune deficiency syndromes that can be quite devastating. If autoreactive cells survive to emerge into the periphery, autoimmunity, either organ-specific or more global, may occur. If B cells in the periphery proliferate in an uncontrolled fashion, a variety of B cell lymphoproliferative syndromes may develop, recognizable by the phenotypic markers of their originating B cell lineage level of differentiation. The full details of how autoreactive B cells survive and thrive, only to cause disease, are not yet clear, but identification of many of the phenotypic surface markers and circulating growth factors identified to this point have borne therapeutic fruit.

Animals↗

PubMed1998

Cell lineage relationship in the stomach of normal and genetically manipulated mice.

The oxyntic mucosa of the mouse stomach is lined with a heterogeneous population of cells that form numerous short pits continuous with long tubular glands. Tritiated thymidine radioautography has made it possible to pinpoint the origin of all cell types and to follow the differentiation/migration of different cell lineages along the pit-gland unit. The proliferating multipotent stem cells functionally anchored in the upper glandular region, the isthmus, give rise to three main lineage precursors: 1) pre-pit cells, which migrate upward to the pit while differentiating into mucus-producing pit cells; 2) pre-neck cells, which migrate downward to the glandular neck while differentiating into mucus-producing neck cells that, by approaching the glandular base, gradually change their phenotype into pepsinogen- and intrinsic factor-producing zymogenic cells; 3) pre-parietal cells, which differentiate into acid-producing parietal cells in the isthmus and then undergo bipolar migration towards the pit and the glandular base. Thus, parietal cells are the only cells that complete their differentiation in the isthmus and then migrate to be scattered throughout the pit-gland unit. To determine whether parietal cells play a role in controlling decisions about cell fate within the pit-gland unit, the gastric epithelium has been examined in transgenic mice expressing the H,K-ATPase beta-subunit-1035 to +24/simian virus 40 large T antigen fusion gene. The blockade in parietal cell differentiation in these mice produces an amplification of lineage precursors, a marked depletion of zymogenic cells and an increase in pit cell census. Ablation of parietal cells in another transgenic mouse model expressing the H,K-ATPase beta-subunit-1035 to +24/diphtheria toxin fragment A fusion gene also produces amplification of lineage precursors, and similar effects on zymogenic and pit cell census. These findings strongly suggest that parietal cells produce regulatory signals that control the cellular differentiation program of both pit and zymogenic cell lineages, and would hopefully improve our ability to identify the cellular pathways leading to malignant transformation.

Animals↗

PubMed2004

[Use of stem cells for myocardial regeneration].

Remodelling of the left ventricle after myocardial infarction is a major cause of the heart failure development with possible death. Despite application of pharmacological, catheter and surgical interventions and the use of new mechanical devices, the myocardium lost during myocardial infarction cannot be regenerated. Implantation of bone-marrow stem cells into the heart might be a new method to restore myocardial viability. In animal experiments, attempts to replace fibrotic zone by transplanting stem cells have regularly succeeded in reconstituting myocardial structure--cardiomyocytes and capillary vessels. Repair of myocardium using bone-marrow derived multipotent stem cells was shown in experimental and in the first few clinical studies. Current status of our knowledge about the use of stem cells in the myocardial regeneration is described in this article, as well as the cautions, which are necessary during early period of this mode of treatment in humans.

Animals↗

PubMed1991

Developmental potential of the earliest precursor cells from the adult mouse thymus.

A new, numerically minute population of cells representing the earliest T precursor cells in the adult mouse thymus has recently been isolated. This population has been shown to be similar to bone marrow hemopoietic stem cells in surface antigenic phenotype and to express moderate levels of CD4. We now show, by fluorescence-activated cell sorting and intrathymic transfer to irradiated mice, that this apparently homogeneous population differs from multipotent stem cells in expressing the surface stem cell antigen 2 (Sca-2), that it differs from most early B lineage cells in lacking B220 and class II major histocompatibility complex expression, and that it binds rhodamine 123 like an activated rather than a quiescent cell. Irradiated recipient mice differing at the Ly 5 locus were used to compare the developmental potential of these early intrathymic precursors with bone marrow stem cells. Only T lineage product cells were detected when the intrathymic precursor population was transferred back into an irradiated thymus. However, when the intrathymic precursor population was transferred intravenously, it displayed the capacity to develop into both B and T lymphoid cells in recipient bone marrow, spleen, and lymph nodes, but no donor-derived myeloid cells were detected. The absence of myeloid and erythroid precursor activity was confirmed by showing that the intrathymic precursor population was unable to develop into myeloid or erythroid spleen colonies on intravenous transfer or to form colonies in an agar culture. These findings indicate that this earliest intrathymic precursor population has become restricted (or strongly biased) to lymphoid lineage development, but not exclusively to T lymphocytes.

Agar↗

PubMed2003

The multifaceted adult epidermal stem cell.

Adult epidermal stem cells renew the epithelial compartment of the skin throughout life and are the most accessible of all adult stem cells. Most importantly, epidermal stem cells can be efficiently cultivated and transplanted, a significant advantage for cell and gene therapy. Recent work has pointed to the hair follicle as the main repository of multipotent stem cells in skin. Hair follicles, which are often affected in the mouse by spontaneous or man-made mutations, have become superb model systems to study the cellular and molecular factors that regulate the proliferation, migration and fate of adult stem cells.

Adult↗

PubMed1998

Ectopic interleukin-5 receptor expression promotes proliferation without development in a multipotent hematopoietic cell line.

The interleukin-5 (IL-5) receptor is a heterodimer that consists of an IL-5 specific alpha subunit and a common ssc chain that is shared with the receptors for granulocyte macrophage colony stimulating factor (GM-CSF) and interleukin-3 (IL-3). In contrast to IL-5, which acts mainly as an eosinophil lineage specific factor in vivo, IL-3 and GM-CSF stimulate the survival, proliferation and development of various hematopoietic cell lineages and also multipotent progenitor cells. IL-5 has little effect on the survival or proliferation of the multipotent stem cell line FDCP-Mix A4 but does promote some eosinophil development. To investigate whether the lineage specificity of IL-5 is due to the restricted expression of the IL-5 receptor alpha subunit we transfected the FDCP-Mix A4 cells with a retroviral vector containing this alpha subunit. The ectopic expression of the IL-5 receptor alpha subunit in the FDCP-Mix cells did not increase the observed eosinophilic development but did stimulate survival and proliferation of the transfected cells when IL-5 was added. IL-5 thus acts like IL-3 in these cells, promoting proliferation and survival. The results suggest that IL-5, whilst having a capacity to promote proliferation, does not influence eosinophilic lineage commitment in these multipotent cells. The results further argue that the observed lineage specificity of IL-5 is probably due to factors in addition to the restricted expression of the IL-5 receptor alpha subunit.

Animals↗

PubMed2003

Haematopoietic stem cells retain long-term repopulating activity and multipotency in the absence of stem-cell leukaemia SCL/tal-1 gene.

The production of blood cells is sustained throughout the lifetime of an individual by haematopoietic stem cells (HSCs). Specification of HSCs from mesoderm during embryonic development requires the stem cell leukaemia SCL/tal-1 gene product. Forced expression of SCL/tal-1 strongly induces blood formation in embryos, indicating that this gene has a dominant role in commitment to haematopoiesis. In the adult haematopoietic system, expression of SCL/tal-1 is enriched in HSCs and multipotent progenitors, and in erythroid and megakaryocytic lineages, consistent with roles for this factor in adult haematopoiesis. Here we assess by conditional gene targeting whether SCL/tal-1 is required continuously for the identity and function of HSCs. We find that SCL/tal-1 is dispensable for HSC engraftment, self-renewal and differentiation into myeloid and lymphoid lineages; however, the proper differentiation of erythroid and megakaryocytic precursors is dependent on SCL/tal-1. Thus, SCL/tal-1 is essential for the genesis of HSCs, but its continued expression is not essential for HSC functions. These findings contrast with lineage choice mechanisms, in which the identity of haematopoietic lineages requires continuous transcription factor expression.

Animals↗

PubMed2005

Plasticity of epidermal stem cells: survival in various environments.

The keratinocyte cell compartment in the continuously renewing epidermis of the skin is maintained by undifferentiated, self-renewing stem cells. We show that a small subpopulation of epidermal stem cells (EpiSCs) have the capacity to integrate into multiple tissues. These EpiSCs can change their phenotype in direct response of changes in cytokines in vitro, changes in cocultured cells, after injection into damaged environments in vivo. These changes appear to be unrelated to the age of the EpiSC. Even though we can isolate these cells and show that the age of thses cells appears to be irrelevant to this multipotent function, we still do not know how such cells are defined within a tissue or what the life span of a multipotent stem cell is.

Animals↗

PubMed2000

Proliferative populations in intestinal metaplasia: evidence of deregulation in Paneth and goblet cells, but not endocrine cells.

In the small intestinal mucosa, four principal epithelial cell lineages are found - the Paneth, goblet, enterocytic, and endocrine cell lineages. These cell lineages are terminally differentiated, non-proliferative, and derive from multipotent stem cells near the bases of the crypts of Lieberkühn. Intestinal metaplasia of the stomach is considered to be a premalignant condition. Since proliferative populations in this condition are not well studied, this feature was examined using double-labelling immunohistochemical and histochemical methods; 20 paraffin blocks of small intestinal mucosa and 24 paraffin blocks of intestinal metaplasia of the human stomach were studied. Double-staining was carried out with MIB-1 as a proliferation marker, with Alcian blue for goblet cells, anti-chromogranin A for endocrine cells, and p-dimethylaminobenzaldehyde-nitrite for Paneth cells. Double-labelling showed that numerous Paneth cells and goblet cells in intestinal metaplasia were in the cell cycle, but endocrine cells appeared non-proliferative. Double-labelled Paneth or endocrine cells were not seen in the control small intestinal mucosa but scanty double-labelled goblet cells were observed in normal intestinal mucosa. In intestinal metaplasia of the stomach, there is evidence of cell-cycle deregulation in the goblet and Paneth cell lineages. These observations have considerable implications for the biology and histogenesis of Paneth cells, goblet cells, and endocrine cells, and the nature of intestinal metaplasia in the gastric mucosa.

Cell Division↗

PubMed2006

The contribution of the neural crest to the vertebrate body.

As a transitory structure providing adult tissues of the vertebrates with very diverse cell types, the neural crest (NC) has attracted for long the interest of developmental biologists and is still the subject of ongoing research in a variety of animal models. Here we review a number of data from in vivo cell tracing and in vitro single cell culture experiments, which gained new insights on the mechanisms of cell migration, proliferation and differentiation during NC ontogeny. We put emphasis on the role of Hox genes, morphogens and interactions with neighbouring tissues in specifying and patterning the skeletogenic NC cells in the head. We also include advances made towards characterizing multipotent stem cells in the early NC as well as in various NC derivatives in embryos and even in adult.

Animals↗