Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Multipotent Stem Cells”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,693 records · Page 94Linked to original sources
PubMed1999

Developmental biology and the redirection or replacement of cells.

The aim of developmental biology is to understand how an egg converts itself into a complete organism through the processes of cell differentiation, morphogenesis and size regulation. The principles that have emerged over recent decades include the constancy of the genome in nearly all cells of an individual, the existence of stem cells in many organs and the overwhelming importance of signalling between cells for the determination of their fate. These and other characteristics of development are discussed here in relation to the prospect of achieving cell and tissue correction or replacement with the help of nuclear transplantation and signalling factors. Nuclear transplantation offers a one-step procedure for generating multipotent embryo cells from the cells of an adult tissue such as skin. It should be possible to proliferate the resulting cells as can be done for mouse embryonic stem cells. Embryo cells can be made to differentiate in many directions by exposing them to various agents or to different concentrations of a single factor such as the transforming growth factor beta class signalling molecule activin. The possibility of a cancerous condition being acquired during these experimental manipulations can be guarded against by transfecting cells with a conditional suicide gene. Thus it may be possible to generate replacement cells or tissues from an adult human for transplantation back to the original donor, without the disadvantage of any genetic incompatibility.

Adult↗
PubMed2006

Hepatic stem cells: in search of.

The field of stem cell biology has exploded with the study of a wide range of cellular populations involving endodermal, mesenchymal, and ectodermal organs. One area of extensive study has included the identification of hepatic stem and progenitor cell subpopulations. Liver stem cells provide insights into the potential pathways involving liver regeneration that are independent of mature hepatocytes. Hepatic progenitor cells are either bipotent or multipotent and capable of multiple rounds of replication. They have been identified in fetal as well as adult liver. Various injury models have been used to expand this cellular compartment. The nomenclature, origin, and function of the hepatic progenitor cell populations are areas of ongoing debate. In this review, we will discuss the different definitions and functions of hepatic progenitor cells as well as the current research efforts examining their therapeutic potential.

Animals↗
PubMed1997

Engraftment of embryonic hematopoietic cells in conditioned newborn recipients.

Yolk sac hematopoiesis is characterized by restricted hematopoietic cell differentiation. Although multipotent hematopoietic progenitor cells have been identified in the early yolk sac, long-term multilineage repopulating (LTMR) hematopoietic stem cell (HSC) activity has not been demonstrable before day 11 postcoitus (PC) using standard transplantation assays. In the present study, day-10 PC yolk sac hematopoietic cells were infused into myeloablated congenic newborn pups and donor cell engraftment and multilineage reconstitution of peripheral blood cells for at least 11 months in primary recipients was observed. In contrast, transplantation of day-10 PC yolk sac cells into congenic adult recipients did not result in engraftment despite pretransplant conditioning of the recipients or use of recipients that were genetically deficient in stem cells. Although fresh yolk sac cells were incapable of reconstitution when injected into adult recipient mice, yolk sac donor-derived cells residing in the bone marrow of primary newborn transplant recipients were capable of efficient reconstitution of conditioned secondary recipient adult mice. Primary newborn and secondary adult recipient animals engrafted with yolk sac cells were observed to have normal peripheral blood white blood cell counts. Lymphocyte subsets in peripheral blood, thymus, and spleen were also similar to control animals. The distribution and frequency of lineage-restricted progenitors derived from bone marrow of secondary transplant recipients were normal. These results indicate that day-10 PC yolk sac HSCs are capable of engrafting and reconstituting the hematopoietic system of conditioned newborn but not adult recipient animals. Furthermore, the ability of the yolk sac HSCs to differentiate into all hematopoietic lineages in these recipients strongly suggests that the local cellular microenvironment plays a prominent role in regulating yolk sac HSC differentiation.

Animals↗
PubMed2002

Lung epithelial stem cells.

This review concentrates on recent evidence about lung stem cell origins and plasticity. The range of potential cells which can repopulate the injured lung, classically the basal and mucous secretory cells of the trachea, the Clara cells of the bronchiole, and the type II pneumocyte of the alveolus, has been extended to include the mucus-gland duct cells of the trachea and bronchus. Some evidence suggests that there are variant Clara cells that lack cytochrome P-450 and so are spared toxic activation of xenobiotics, and may aid bronchiolar repopulation after injury, such as with naphthalene. There may even be involvement of the neuroepithelial bodies or cells in this, though the evidence is not yet conclusive. The search for a resident pulmonary multipotent cell for repopulating any lung epithelium has not yet been successful. The picture remains similar to earlier conclusions, in that the local stem or precursor cell is the most likely to contribute to local needs in times of tissue damage. There remains a major challenge for lung cancer treatment, where high-dose chemo- or radio-therapy may be hoped to promote the seeding and repair of lung parenchyma by circulating bone marrow stem cells, as seen in liver models. Patient survival rates do not yet suggest that this occurs to any great extent, but this remains to be shown formally. The effects of prior fibrosis and tumour necrosis are probably confounding factors in this lack of rescue.

Animals↗
PubMed2006

Isolation, cultivation, and differentiation of neural stem cells from adult fish brain.

In contrast to mammals, teleost fish are distinct in their ability to continuously produce a tremendous number of new neurons in many regions of the adult brain. In the present study, we have isolated intrinsic stem cells from the telencephalon, corpus cerebelli, and valvula cerebelli of the teleost Apteronotus leptorhynchus and examined their properties in vitro. After 3-4 days in culture, neurospheres developed that grew through cell proliferation and reached diameters of up to 140 microm within 3 weeks. An increase in the number of developing neurospheres could be promoted by addition of epidermal growth factor or basic fibroblast growth factor, but no additive effect was observed after combined treatment. The number of neurospheres could furthermore be enhanced by seeding brain cells at densities of approximately 1 x 10(6). Differentiation conditions were optimal by exposing neurospheres to 10% fetal bovine serum and laminin as coating substrate. Neurosphere cells gave rise to both neurons, immunopositive for Hu-C/D or MAP2 (2a + 2b), and glial cells, immunopositive for glial fibrillary acidic protein or vimentin. Since, in addition to their multipotency, the cells isolated from the adult teleostean brain exhibited the ability for self-renewal, we hypothesize that they are true stem cells.

Animals↗
PubMed1994

Glial growth factor restricts mammalian neural crest stem cells to a glial fate.

Growth factors and cytokines are thought to influence the development of uncommitted progenitor cell populations, but the issue of how these factors act on individual cells remains controversial. Such factors may act simply as selective mitogens or survival factors for cells that undergo lineage restrictions stochastically. Alternatively, they may instruct or bias multipotent cells to choose one lineage at the expense of others. Here we show that glial growth factor (GGF), previously defined as a Schwann cell mitogen, strongly suppresses neuronal differentiation of rat neural crest stem cells while promoting or allowing glial differentiation. Quantitative clonal analysis suggests that the action of GGF is likely to be instructive rather than selective. Taken together with the expression pattern of GGF, these data suggest a lateral signaling model for the diversification of cell types within developing peripheral ganglia.

Animals↗
PubMed1998

A common neural progenitor for the CNS and PNS.

Cultured spinal cord neuroepithelial (NEP) cells can differentiate into neurons, oligodendrocytes and astrocytes and are morphologically and antigenically distinct from neural crest stem cells (NCSCs) that generate the PNS. NEP cells, however, can generate p75/nestin-immunoreactive cells that are morphologically and antigenically similar to previously characterized NCSCs. NEP-derived p75-immunoreactive cells differentiate into peripheral neurons, smooth muscle, and Schwann cells in mass and clonal culture. Clonal analysis of NEP cells demonstrates that a common NEP progenitor cell generated both CNS and PNS phenotypes. Differentiation into NCSCs was promoted by BMP-2/4 and differentiation did not require cells to divide, indicating that BMP played an instructive role in the differentiation process. Thus, individual NEP cells are multipotent and can differentiate into most major types of cell in the CNS and PNS and that PNS differentiation involves a transition from a NEP stem to another more limited, p75-immunoreactive, neural crest stem cell.

Animals↗
PubMed2004

[Stem cells: biology and possible application to myocardial infarct].

If the heart fails to recover sufficient functionality following an infarct, then heart failure develops, an important cause of death in the western world. One obvious therapy is to create more muscle tissue to supplement the damaged myocardium with new functional contractile cells, together with neovasculogenesis. Stem cells repair recipient tissue by differentiating into tissue-specific cells or by creating an environment that stimulates the process of repair by the body's own cells at the site. In animal studies the heart function stabilised following an injection of stem cells in the infarcted area. In 3 non-randomised trials in humans, bone marrow stem cells were injected via the infarcted artery or round the infarcted area; the results indicated an improved heart function. There is currently still insufficient fundamental knowledge about the behaviour of multipotent cells, about the effects of using them for treatment, and about their long-term risk for these cells to be employed in the treatment of patients with a heart infarct.

Heart↗
PubMed2002

Hematopoietic, vascular and cardiac fates of bone marrow-derived stem cells.

Bone marrow contains many cell types, including stroma, vascular cells, adipocytes, osteoblasts and osteoclasts, as well as mesenchymal stem cells and hematopoietic stem cells. It was previously thought that cells within bone marrow solely functioned to regenerate cells within the marrow, as well as all circulating hematopoietic cells in peripheral blood. Recent reports, however, suggest that marrow-derived cells can also regenerate other cell types, including cardiac muscle, liver cell types, neuronal and non-neuronal cell types of the brain, as well as endothelial cells and osteoblasts. These multiple cell types could have originated from either of the stem cell populations within bone marrow or potentially other precursors. Therefore, it is not entirely clear whether each of these distinct cell lineages has a true progenitor within marrow or whether the marrow contains a multipotent population of cells that has been set aside during embryogenesis for postnatal repair and remodeling of a variety of tissues. It is clear, however, that directing the fate of bone marrow-derived progenitors (ie toward hematopoietic, vascular or cardiac cell fates) can only be accomplished if the phenotype of the stem cells is defined, and their homing and differentiation programs are elucidated. Much work is focused on these issues, wherein lie the key to harnessing the potential of adult stem cells for autologous cell and gene therapy.

Adult↗
PubMed2000

Adult spinal cord stem cells generate neurons after transplantation in the adult dentate gyrus.

The adult rat spinal cord contains cells that can proliferate and differentiate into astrocytes and oligodendroglia in situ. Using clonal and subclonal analyses we demonstrate that, in contrast to progenitors isolated from the adult mouse spinal cord with a combination of growth factors, progenitors isolated from the adult rat spinal cord using basic fibroblast growth factor alone display stem cell properties as defined by their multipotentiality and self-renewal. Clonal cultures derived from single founder cells generate neurons, astrocytes, and oligodendrocytes, confirming the multipotent nature of the parent cell. Subcloning analysis showed that after serial passaging, recloning, and expansion, these cells retained multipotentiality, indicating that they are self-renewing. Transplantation of an in vitro-expanded clonal population of cells into the adult rat spinal cord resulted in their differentiation into glial cells only. However, after heterotopic transplantation into the hippocampus, transplanted cells that integrated in the granular cell layer differentiated into cells characteristic of this region, whereas engraftment into other hippocampal regions resulted in the differentiation of cells with astroglial and oligodendroglial phenotypes. The data indicate that clonally expanded, multipotent adult progenitor cells from a non-neurogenic region are not lineage-restricted to their developmental origin but can generate region-specific neurons in vivo when exposed to the appropriate environmental cues.

Animals↗
PubMed1995

Postmigratory neural crest cells expressing c-RET display restricted developmental and proliferative capacities.

c-RET is an orphan receptor tyrosine kinase essential for enteric neurogenesis in mice and is involved in several human genetic disorders. RET is also one of the earliest surface markers expressed by postmigratory neural crest cells in the gut. We generated anti-RET monoclonal antibodies to isolate such cells. We find that RET+ cells are antigenically and functionally distinct from neural crest stem cells (NCSCs) characterized previously. Unlike NCSCs, which are RET- and MASH1-, most RET+ cells express MASH1. Moreover, unlike NCSCs, which are multipotent and have high proliferative capacity, many RET+ cells generate only neurons following a limited number of divisions. This behavior is observed even in the presence of glial growth factor, a polypeptide that suppresses neuronal and promotes glial differentiation by NCSCs. These data provide direct evidence for the existence of committed neuronal progenitor cells and support a model of neural crest lineage diversification by progressive restriction of developmental potential.

Animals↗
PubMed2003

Expression of BCR/ABL and BCL-2 in myeloid progenitors leads to myeloid leukemias.

Chronic myelogenous leukemia is a myeloproliferative disorder (MPD) that, over time, progresses to acute leukemia. Both processes are closely associated with the t(9;22) chromosomal translocation that creates the BCR/ABL fusion gene in hematopoietic stem cells (HSCs) and their progeny. Chronic myelogenous leukemia is therefore classified as an HSC disorder in which a clone of multipotent HSCs is likely to be malignantly transformed, although direct evidence for malignant t(9;22)+ HSCs is lacking. To test whether HSC malignancy is required, we generated hMRP8p210BCR/ABL transgenic mice in which expression of BCR/ABL is absent in HSCs and targeted exclusively to myeloid progenitors and their myelomonocytic progeny. Four of 13 BCR/ABL transgenic founders developed a chronic MPD, but only one progressed to blast crisis. To address whether additional oncogenic events are required for progression to acute disease, we crossed hMRP8p210BCR/ABL mice to apoptosis-resistant hMRP8BCL-2 mice. Of 18 double-transgenic animals, 9 developed acute myeloid leukemias that were transplantable to wild-type recipients. Taken together, these data indicate that a MPD can arise in mice without expression of BCR/ABL in HSCs and that additional mutations inhibiting programmed cell death may be critical in the transition of this disease to blast-crisis leukemia.

Animals↗
PubMed2006

FGF-2 inhibits osteogenesis in mouse adipose tissue-derived stromal cells and sustains their proliferative and osteogenic potential state.

In addition to adult bone marrow-derived mesenchymal stem cells, more recently, a second large stromal compartment found in adipose tissue has received attention and is believed to contain multipotent cells. In vitro, adipose tissue-derived stromal cells (ADS) can differentiate down osteogenic, chondrogenic, myogenic, adipose, and even neuronal pathways. In this article, we explore the effect of fibroblast growth factors 2 (FGF-2) on ADS cells. Our results demonstrated that FGF-2 inhibits osteogenesis in ADS cells. The osteogenic inhibitory effects is dose-dependent and reversible, thus suggesting that the lack of osteogenesis observed in ADS cells exposed to FGF-2 is not due to a negative selection triggered by this factor on a subpopulation of osteoblast progenitors. Furthermore, either overexpression of FGF-2, or continuous FGF-2 treatment sustain the proliferative and osteogenic potential state of ADS cells. Therefore, FGF-2 appears to be a positive regulator of osteoprogenitor cells and a negative regulator of osteoblast differentiation in ADS cells. These FGF-2 functional characteristics may assist with cell selection and enrichment for the purpose of bone tissue engineering.

Adipose Tissue↗
PubMed2000

Expression of notch receptors, notch ligands, and fringe genes in hematopoiesis.

OBJECTIVE: Hematopoiesis is the process by which mature blood cell types are generated from a small population of pluripotent hematopoietic stem cells. How these cells undergo fate selection, however, is not fully understood. The Notch signaling system is known to mediate cell fate decisions of multipotent precursors in a wide range of complex animals throughout development. As Notch signaling involves cell-cell interactions, we sought to determine the expression of Notch receptors, ligands, and regulators in individual cell populations along the hematopoietic differentiation pathway. MATERIALS: Described here is a single cell RT-PCR analysis of Notch1, Notch3, Notch4, Notch ligands (Dll1 and Jagged1), and Fringe gene expression in cells of the blood system. As previously described, single cell globally amplified cDNA was generated by RT-PCR from various hematopoietic precursor cells whose potential was known from sibling analysis. A precursor hierarchy slot blot was created containing these cDNAs as well as samples from maturing blood cell populations and two fibroblast cell lines. The precursor slot blot was screened with probes for each of the candidate genes. RESULTS: Macrophage precursors expressed high levels of Notch1 transcript, while maturing macrophages expressed high levels of both Notch1 and Notch4. The Jagged 1 ligand transcript was highly expressed in terminally maturing cells including mast cells and megakaryocytes. In contrast, the Manic Fringe gene was highly expressed in uncommitted bi- and tri-potential precursors as well as in committed neutrophil and macrophage precursors. CONCLUSIONS: Distinct expression patterns of Jagged1 and Manic Fringe suggest that their corresponding proteins could regulate cell fate choices during hematopoiesis and may be responsible for regulating communication between lineage compartments during hematopoietic development.

Animals↗
PubMed2000

The homeodomain protein PRH influences the differentiation of haematopoietic cells.

Haematopoiesis involves the differentiation of a self-renewing stem cell into all of the lineages found in circulating blood. Myb-Ets transformed chicken blastoderm cells (MEPs) have many of the characteristics of multipotent haematopoietic cells and represent a useful model system for the study of haematopoiesis. The proline-rich homeodomain protein (PRH) has previously been shown to be expressed in the haematopoietic compartment. In this report we show that PRH mRNA and protein levels are down regulated as MEPs differentiate along the myelomonocytic and erythrocytic lineages. In contrast, PRH mRNA and protein levels remain high as MEPs differentiate toward the thrombocytic lineage. Over-expression of full length PRH in MEPs inhibits their transformation and/or proliferation. However, the over-expression of N-terminally truncated PRH proteins results in normally proliferating cells that are predominantly differentiated along the myelomonocytic and eosinophilic lineages. These results suggest that PRH plays a role in the proliferation and differentiation of haematopoietic cells.

Cell Differentiation↗
PubMed1995

Basic fibroblast growth factor mediates its effects on committed myeloid progenitors by direct action and has no effect on hematopoietic stem cells.

Basic fibroblast growth factor or fibroblast growth factor-2 (FGF) has been shown to affect myeloid cell proliferation and hypothesized to stimulate primitive hematopoietic cells. We sought to evaluate the effect of FGF on hematopoietic stem cells and to determine if FGF mediated its effects on progenitor cells directly or through the induction of other cytokines. To address the direct effects of FGF, we investigated whether FGF induced production of interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha, IL-6, granulocyte colony-stimulating factor, or granulocyte-macrophage colony-stimulating factor by two types of accessory cells, bone marrow (BM) fibroblasts and macrophages. We further evaluated whether antibodies to FGF-induced cytokines affected colony formation. To determine if FGF was capable of stimulating multipotent progenitors, we assessed the output of different colony types after stimulation of BM mononuclear cells (BMMC) or CD34+ BMMC and compared the effects of FGF with the stem cell active cytokine, kit ligand (KL). In addition, a subset of CD34+ BMMC with characteristics of hematopoietic stem cells was isolated by functional selection and their response to FGF was evaluated using proliferation, colony-forming, and single-cell polymerase chain reaction (PCR) assays. We determined that FGF had a stimulatory effect on the production of a single cytokine, IL-6, but that the effects of FGF on colony formation were not attributable to that induction. FGF was more restricted in its in vitro effects on BM progenitors than KL was, having no effect on erythroid colony formation. FGF did not stimulate stem cells and FGF receptors were not detected on stem cells as evaluated by single-cell reverse transcription PCR. In contrast, FGF receptor gene expression was detected in myeloid progenitor populations. These data support a directly mediated effect for FGF that appears to be restricted to lineage-committed myeloid progenitor cells. FGF does not appear to modulate the human hematopoietic stem cell.

Adipose Tissue↗
PubMed2001

High-yield selection and extraction of two promoter-defined phenotypes of neural stem cells from the fetal human brain.

Neural stem and precursor cells reside in the ventricular lining of the fetal forebrain, and may provide a cellular substrate for brain repair. To selectively identify and extract these cells, we infected dissociated fetal human brain cells with adenoviruses bearing the gene for green fluorescence protein (GFP), placed under the control of enhancer/promoters for two genes (nestin and musashi1) that are expressed in uncommitted neuroepithelial cells. The cells were then sorted by fluorescence-activated cell sorting (FACS) on the basis of E/nestin- or P/musashi1-driven GFP expression. Both P/musashi1:hGFP- and E/nestin:EGFP-sorted cells were multipotent: limiting dilution with clonal expansion as neurospheres, in tandem with retroviral lineage analysis and xenograft to E17 and P0-2 rat forebrain, revealed that each phenotype was able to both self-renew and co-generate neurons and glia. Thus, fluorescent genes placed under the control of early neural promoters allow neural stem cells to be specifically targeted, isolated, and substantially enriched from the fetal human brain.

Adenoviridae↗