Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “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 73 records · Page 4Linked to original sources
PubMed2006

Melanoma, a tumor based on a mutant stem cell?

Stem cells play a critical role in normal tissue maintenance, and mutations in these stem cells may give rise to cancer. We hypothesize that melanoma develops from a mutated stem cell and therefore residual stem cell characteristics should be able to be identified in melanoma cell lines. We studied three metastatic melanoma cell lines that exhibited multiple morphologic forms in culture and demonstrated the capacity to pigment. We used the ability to efflux Hoechst 33342 dye, a technique known to enrich for stem cells in many tissues, to segregate cell populations. The cells with the greatest ability to efflux the dye were (1) small in size, (2) had the capacity to give rise to larger cell forms, and (3) had the greatest ability to expand in culture. The small cells were found to have a decreased proliferative rate and were less melanized. Large dendritic cells that appeared to be nonproliferative were identified in cultures. Treatment with cytosine beta-D-arabinofuranoside hydrochloride (Ara-C) expanded the large cell population but the residual proliferative capacity, both in vitro and in vivo, remained concentrated in the smaller cell fraction. Antigenic staining patterns were variable and heterogeneous. Nestin (a neural stem cell marker) and gp100 (premelanosomal marker) favored the smaller cell population, while nerve growth factor receptor often labeled larger cells. Morphologic and antigenic heterogeneity remained intact after clonal purification. These findings are consistent with the behavior expected for a tumor based on stem cell biology; this finding has diagnostic and therapeutic implications for melanocytic neoplasias.

Antigens, Neoplasm↗
PubMed2004

The clinical potential of stem cells.

Stem cells are defined by their capacity for self-renewal and multilineage differentiation, making them uniquely situated to treat a broad spectrum of human diseases. For example, because hematopoietic stem cells can reconstitute the entire blood system, bone marrow transplantation has long been used in the clinic to treat various diseases. Similarly, the transplantation of other tissue-specific stem cells, such as stem cells isolated from epithelial and neural tissues, can treat mouse disease models and human patients in which epithelial and neural cells are damaged. An alternative to tissue-specific stem cell therapy takes advantage of embryonic stem cells, which are capable of differentiating into any tissue type. Furthermore, nuclear transfer, the transfer of a post-mitotic somatic cell nucleus into an enucleated oocyte, creates a limitless source of autologous cells that, when combined with gene therapy, can serve as a powerful therapeutic tool.

Animals↗
PubMedDate not supplied

Stem cells.

Stem cells derived from adult and embryonic sources have great therapeutic potential, but much research is still needed before their clinical use becomes commonplace. There is debate about whether adult stem cells can be used instead of those derived from embryos. Rationalisation is needed but can be exercised only once the various cells have been carefully compared and contrasted under appropriate experimental conditions. Some characteristics that might help resolve the issue of cell source can already be applied to the debate. Accessibility is important; some adult cells, such as neural stem cells, are difficult to obtain, at least from living donors. Other factors include the frequency and abundance of adult stem cells and their numbers and potency, which might decline with age or be affected by disease. For embryonic stem cells, ethical concerns have been raised, and the proposed practice of therapeutic cloning tends to be misrepresented in the lay media. For both adult and embryonic stem cells, stability, potential to transmit harmful pathogens or genetic mutations, and risk of forming unwanted tissues or even teratocarcinomas have yet to be fully assessed.

Cell Differentiation↗
PubMed2004

Local environmental factors determine hematopoietic differentiation of neural stem cells.

Stem cells exhibit unique properties and hold high therapeutic promise, but factors influencing their differentiation after transplantation need to be recognized and defined for this promise to be fully met. Here, we demonstrate that endogenous colony-forming unit spleen (CFU-S) colonies are not generated in lethally irradiated mice transplanted with neural stem cells obtained from brain tissue of syngeneic donors. We investigated the proportion of transplanted neural stem cells that contributed to hematopoietic reconstitution and compared the distribution of transplanted cells in nonsplenectomized to that of splenectomized mice following sublethal whole-body irradiation. We also used clonogenic assays, colony assays, and histochemical analyses to explore conditions under which transplanted, beta-galactosidase-tagged neural stem cells underwent hematopoietic differentiation. Our results suggest that neural stem cells do undergo extramedullary hematopoiesis, even while no endogenous hematopoietic colonies develop in the spleen. Furthermore, we found that neural stem cells effectively colonized the bone marrow of splectomized recipients. We conclude that the hematopoietic differentiation of neural stem cells is highly dependent on the extramedullary environment. We also conclude that the bone marrow does not provide an environment supportive of hematopoietic differentiation by neural stem cells.

Animals↗
PubMedDate not supplied

Physical and physiological plasticity of hematopoietic stem cells.

Stem cells from a variety of tissues have recently been shown to be capable of differentiating into cells characteristic of a separate tissue, apparently in response to microenvironmental signals. This is hierarchical plasticity. We have shown that both human and murine neurosphere cells with potential for differentiating into neurons, oligodendrocytes, and astrocytes can produce hematopoietic stem cells when engrafted into fetal sheep or murine day 3.5 blastocysts, respectively. We have also demonstrated an alternative form of stem cell plasticity: functional plasticity at different points in cell cycle transit and at different phases of a circadian rhythm. We have shown that long-term engraftment varies reversibly as primitive murine stem cells (lineage-negative rhodamine(low) Hoechst(low)) transit the cell cycle under stimulation by interleukin-3 (IL-3), IL-6, IL-11, and steel factor, with engraftment being defective in late S/early G2. Engraftment also varies markedly with circadian time. Presumptive mechanisms for these phenotypic shifts include alteration in adhesion protein expression with consequent changes in marrow homing. Most recently, we have also demonstrated that stem cell differentiation varies markedly with cell cycle transit. There are other features of the hematopoietic stem cell which suggest that it is a highly plastic cell with the ability to rapidly change its membrane phenotype, while exhibiting extraordinary directed motility. These data suggest that cell cycle and circadian plasticity should be considered additional major features of the hematopoietic stem cell phenotype.

Animals↗
PubMed2005

Generation of insulin-producing cells from stem cells.

Islet transplantation as a potential treatment for diabetes will always be limited mainly because of the difficulty in obtaining sufficiently large numbers of purified islets from cadaveric donors. One alternative to organ or tissue transplantation is the use of a renewable source of cells. Stem cells are clonogenic cells capable of both self-renewal and multilineage differentiation. Therefore, these cells have the potential to proliferate and differentiate into any type of cell and to be genetically modified in vitro, thus providing cells which can be isolated and used for transplantation. Moreover, these derived cells have proven to be useful in different animal models. In this regard, insulin-secreting cells derived from mouse embryonic stem cells normalize blood glucose when transplanted into streptozotocin-induced diabetic animals. Using a combination of several differentiation methods and a 'cell trapping' system, we have obtained insulin-secreting cells from undifferentiated embryonic stem cells. The construct used allows the expression of a neomycin selection system under the control of the regulatory regions of insulin gene and other beta cell genes, such as Nkx6.1. Transplanted animals correct hyperglycaemia within 1 week and restore body weight in four weeks. Graft removal rescued the diabetic condition. Glucose tolerance test (IPGTT) and blood glucose normalization after a challenge meal was similar in control and in transplanted animals. This approach opens new possibilities for tissue transplantation in the treatment of type 1 and 2 diabetes.

Animals↗
PubMed2004

Regulation of intestinal stem cells.

Stem cells are essential for maintaining the tissue integrity of all adult tissues. The manipulation of adult stem cells has the potential for cell regeneration and in curing diseases; however, the intestinal stem cell remains enigmatic. Although much work has focused on characterization of the intestinal stem cell within its in vivo niche, the lack of reliable markers complicates its isolation and therefore its in vitro manipulation. Understanding what regulates the intestinal stem cell within its niche will provide valuable insight into how these cells can be manipulated in culture. Comparing the regulation of this niche in the developing and mature intestine is a valuable untapped resource. A small number of signaling pathways are functionally conserved during development. These pathways are beginning to emerge as critical regulators of the stem cell niche. This review focuses on the regulation of the intestinal stem cell niche.

Animals↗
PubMed2002

Plasticity, niches, and the use of stem cells.

Stem cells possess the ability to self-renew and generate multiple cell types of the tissues in which they reside. Several studies have reported transdifferentiation events between different somatic stem cells. These properties have created tremendous excitement about the prospect of using stem cells from easily accessible sources for tissue engineering. However, recently, the plasticity of stem cells has met with several strong challenges. In this meeting review, we will discuss issues surrounding reports of transdifferentiation, the molecular mechanisms that govern stem cell states, and progress toward putting stem cells to use.

Animals↗
PubMed1988

Multiparameter analysis of transplantable hemopoietic stem cells. II. Stem cells of long-term bone marrow-reconstituted recipients.

Marrow obtained from mice (referred to as [X + BM] mice) 3 months after gamma-irradiation (9 Gy) and bone marrow inoculation (0.1 femur equivalents) showed a reduced capacity to reconstitute hemopoiesis of irradiated mice and an increased sensitivity to 5-fluorouracil. Sorting of marrow from (X + BM) mice on the basis of low angle and 90 degrees scatter, and low rhodamine 123 fluorescence, showed that the set of cells that in normal mice is enriched for cells efficient at hemopoietic reconstitution manifested the greatest reduction in hemopoietic reconstituting ability. In spite of this reduction this fraction contained as many 13-day spleen colony-forming units (CFU-S13) and high proliferative potential colony-forming cells (HPP-CFC) as the equivalent fraction from normal littermate mice. This could be explained by postulating that neither CFU-S13 nor HPP-CFC are responsible for hemopoietic reconstitution, but that this is dependent on an earlier, pre-CFU-S13 cell. Alternatively only a subset of either CFU-S13 or HPP-CFC is responsible for long-term hemopoietic reconstitution after lethal irradiation. It would appear that at present there is no adequate method of predicting the hemopoietic reconstituting ability of a given marrow, other than to test it by injection into lethally irradiated hosts.

Animals↗
PubMed2005

The molecular repertoire of the 'almighty' stem cell.

Stem cells share the defining characteristics of self-renewal, which maintains or expands the stem-cell pool, and multi-lineage differentiation, which generates and regenerates tissues. Stem-cell self-renewal and differentiation are influenced by the convergence of intrinsic cellular signals and extrinsic microenvironmental cues from the surrounding stem-cell niche, but the specific signals involved are poorly understood. Recently, several studies have sought to identify the genetic mechanisms that underlie the stem-cell phenotype. Such a molecular road map of stem-cell function should lead to an understanding of the true potential of stem cells.

Animals↗
PubMed2005

Multipotent adult progenitor cell and stem cell plasticity.

Stem cells are defined by their biological function. A stem cell is an undifferentiated cell that self-renews to maintain the stem cell pool and at the single-cell level differentiates into more than one mature, functional cell. In addition, when transplanted, a stem cell should be capable of replacing a damaged organ or tissue for the lifetime of the recipient. Some would argue that stem cells should also be capable of functionally integrating into nondamaged tissues. Stem cells are critical to both embryogenesis and postnatal life.

Adult↗
PubMed2003

An empty Drosophila stem cell niche reactivates the proliferation of ectopic cells.

Stem cells are thought to reside in regulatory microenvironments ("niches") generated by stable stromal neighbors. To investigate the significance of empty niches vacated by stem cell loss, we studied Drosophila ovarioles, which maintain two to three germ-line stem cells in a niche requiring adhesive stromal cap cells and Decapentaplegic signals. After experimentally emptying the germ-line stem cell niche, cap cell activity persists for several weeks. Initially, somatic inner germarium sheath cells enter the empty niche, respond to Dpp, but fail to divide. Subsequently, follicle cell progenitors, including somatic stem cells enter the niche, respond to Dpp, and proliferate as long as cap cells remain. Proliferation requires the normal hedgehog signal of the somatic stem cells as well as proximity to the niche. Thus, empty niches can persist, signal incoming cells, and support ectopic proliferation. Similar events may underlie some disease states.

Animals↗
PubMed2006

Bone marrow mesenchymal stem cells are progenitors in vitro for inner ear hair cells.

Stem cells have been demonstrated in the inner ear but they do not spontaneously divide to replace damaged sensory cells. Mesenchymal stem cells (MSC) from bone marrow have been reported to differentiate into multiple lineages including neurons, and we therefore asked whether MSCs could generate sensory cells. Overexpression of the prosensory transcription factor, Math1, in sensory epithelial precursor cells induced expression of myosin VIIa, espin, Brn3c, p27Kip, and jagged2, indicating differentiation to inner ear sensory cells. Some of the cells displayed F-actin positive protrusions in the morphology characteristic of hair cell stereociliary bundles. Hair cell markers were also induced by culture of mouse MSC-derived cells in contact with embryonic chick inner ear cells, and this induction was not due to a cell fusion event, because the chick hair cells could be identified with a chick-specific antibody and chick and mouse antigens were never found in the same cell.

Actins↗
PubMed2006

Dynamic changes of gangliosides expression during the differentiation of embryonic and mesenchymal stem cells into neural cells.

Stem cells are used for the investigation of developmental processes at both cellular and organism levels and offer tremendous potentials for clinical applications as an unlimited source for transplantation. Gangliosides, sialic acid-conjugated glycosphingolipids, play important regulatory roles in cell proliferation and differentiation. However, their expression patterns in stem cells and during neuronal differentiation are not known. Here, we investigated expression of gangliosides during the growth of mouse embryonic stem cells (mESCs), mesenchymal stem cells (MSCs) and differentiated neuronal cells by using high-performance thin-layer chromatography (HPTLC). Monosialoganglioside 1 (GM1) was expressed in mESCs and MSCs, while GM3 and GD3 were expressed in embryonic bodies. In the 9-day old differentiated neuronal cells from mESCs cells and MSCs, GM1 and GT1b were expressed. Results from immunostaining were consistent with those observed by HPTLC assay. These suggest that gangliosides are specifically expressed according to differentiation of mESCs and MSCs into neuronal cells and expressional difference of gangliosides may be a useful marker to identify differentiation of mESCs and MSCs into neuronal cells.

Animals↗
PubMed2005

Normal and neoplastic stem cells.

Stem cells are cells that at the single cell level both self-renew and give rise to differentiated progeny. Self renewal is the property that distinguishes stem cells and progenitors, and in the blood-forming system explains why haematopoietic stem cells (HSCs), not progenitors, are the only cells capable of providing rapid and sustained regeneration of the blood-forming system after ablation by cancer chemo- and radiotherapies. Cancer-free prospectively purified HSCs regenerate the haematopoietic system of patients as rapidly as a marrow or mobilized blood transplant, but without the risk of re-seeding the body with cancer cells. Further, purified allogeneic HSCs can establish donor-specific tolerance to subsequent tissue grafts. However, in contrast to widely-publicized reports of HSC plasticity, we have not been able to show transdifferentiation of HSC to muscle, heart, brain or gut, and conclude that rare cell fusions and incomplete purifications are likely explanations for the other published results. The ability to self-renew is also potentially dangerous, as poorly regulated self renewal is, we believe, a central lesion in all cancers. We have recently shown that myeloid leukaemias in mouse and human are often driven by rare leukaemia (cancer) stem cells which are at the progenitor stage of differentiation, but have activated the self-renewing cell division pathway normally used only by HSCs. Similar cancer stem cells have been isolated in other tumours.

Animals↗
PubMed1999

Studies on the phenotype of migrant thymic stem cells.

Stem cells first enter the thymus around the 11th to 12th days of gestation in BALB/c mouse embryos. The phenotype of these stem cells has been difficult to determine because their entry occurs when the thymic primordium is very small and involves too few stem cells to allow studies by flow cytometry. We have been able to microdissect the thymus from embryos during this stage and immunophenotype cells in sections using a sensitive tyramide amplification system. Our results show that migrant stem cells express CD45, c-kit, CD44, CD34 and alpha4 integrin, but other markers such as CD62L, CD25, Thy-1.2, CD3epsilon, alpha5 integrin and RAG-1 expression are detected only after stem cell entry. These results should help to improve the isolation and characterization of migrant thymic stem cells.

Animals↗