PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Multipotent Stem Cells”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

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

At least 541 records · Page 30Linked to original sources
PubMed2006

The order of expression of transcription factors directs hierarchical specification of hematopoietic lineages.

The mechanism of lineage specification in multipotent stem cells has not been fully understood. We recently isolated progenitors with the eosinophil, basophil, or mast cell lineage potential, all of which originate from granulocyte/monocyte progenitors (GMPs). By using these prospectively purified progenitors, we show here that the expression timing of GATA-2 and CCAAT enhancer-binding protein alpha (C/EBPalpha) can differentially control their lineage commitment. The expression of GATA-2 instructed C/EBPalpha-expressing GMPs to commit exclusively into the eosinophil lineage, while it induced basophil and/or mast cell lineage commitment if C/EBPalpha was suppressed at the GMP stage. Furthermore, simply by switching the order of C/EBPalpha and GATA-2 transduction, even lymphoid-committed progenitors recaptured these developmental processes to be reprogrammed into each of these lineages. We propose that the order of expression of key transcription factors is critical for their interplay to selectively drive lineage specification programs, by which stem cells could generate multiple lineage cells in a hierarchical manner.

Animals↗
PubMed2004

Decrease of nuclear reactivity to growth-regulatory galectin-1 in senescent human keratinocytes and detection of non-uniform staining profile alterations upon prolonged culture for galectin-1 and -3.

Summary Multipotent stem cells (source for interfollicular epidermis, hairs and sebaceous glands) are localized in the bulge region of the outer root sheath of hair follicles, while stem cells giving rise to interfollicular epidermis reside in its basal. Using the multifunctional lectin galectin-1 as a marker to localize accessible binding sites in situ as a step to figure out galectin functionality in stem cells, we studied hair follicle-derived keratinocytes. Specific nuclear binding of galectin-1 associated with expression of DeltaNp63alpha, a potential marker of epidermal stem cells, was detected. Binding of chimera-type galectin-3 to a nuclear site was not found in parallel assays. During the process of ageing in culture when cells acquire properties of senescence, disappearance of the nuclear signal for galectin-1 binding was accompanied by a similar decrease of nuclear DeltaNp63alpha expression and increased binding of galectin-3 to the cell membrane, namely in regions of intercellular contacts. Expression of cytokeratin 10, a marker of the terminal differentiation was seen only in a small fraction of the cell population. These data extend the evidence for nuclear sites with galectin-1 reactivity in squamous epithelial cells, the expression of which is modulated upon senescence. Moreover, the results document the divergence of galectin-1 and -3 on the level of ligand selection in this cell type, underscoring the importance of the technical aspect to employ tissue lectins as probe and to perform a fingerprinting with several markers of the galectin family in parallel.

Aging↗
PubMedDate not supplied

Somatic stem cell research for neural repair: current evidence and emerging perspectives.

Recent evidence supports the existence of adult mammalian stem cell subpopulations, particularly within the bone marrow, that may be able to "transdifferentiate" across tissue lineage boundaries, thus offering an accessible source for therapeutic applications even for neural tissue repair. However, the difficulties in reproducing some experimental data, the rarity of the transdifferentiation events and observations that cell fusion may be an alternative explanation argue against the idea of stem cell plasticity. Investigations going beyond descriptive experiments and more mechanicistic approaches may provide a more solid foundation to adult stem cell therapeutic potential.

Animals↗
PubMed2007

The leading edge of stem cell therapeutics.

Stem cells, by virtue of their defining property of self-renewal, represent an unlimited source of potentially functional human cells for basic research and regenerative medicine. Having validated the feasibility of cell-based therapeutic strategies over the past decade, mostly through the use of rodent cells, the stem cell field has now embarked upon a detailed characterization of human cells. Recent progress has included improved cell culture conditions, long-term propagation, directed differentiation, and transplantation of both human embryonic and somatic stem cells. Continued progress in understanding basic human stem cell biology, combined with a better handle on the fundamental pathophysiology of human diseases one wishes to target (including the use of human stem cells in primate and other large animal models of human disease), should help to move this technology closer to clinical application.

Brain Diseases↗
PubMed1994

Essential thrombocythemia terminating in acute leukemia with minimal myeloid differentiation--a brief review of recent literature.

Essential thrombocythemia (ET), one of the chronic myeloproliferative disorders, is a clonal disorder of multipotent stem cells. Although most patients with ET have a prolonged benign course, a minority of patients may develop a blastic crisis similar to chronic myelogenous leukemia (CML). A case of ET terminating in blastic crisis 8 years after the initial diagnosis is presented. The blast cells were cytochemically and immunophenotypically consistent with the acute myelogenous leukemia with minimal myeloid differentiation subtype of the FAB classification. From the review of the literature on blastic transformation of ET, acute leukemia with an M4 or M7 phenotype occurred more frequently. In addition, three valuable factors to predict the leukemic transformation of ET appear to be karyotypic abnormalities, such as involvement of chromosome 21, previous therapies with a mutagenic potential, and the capability of bone marrow cells to form in vitro spontaneous colonies as in CML.

Acute Disease↗
PubMed2002

IL-3-induced enhancement of retinoic acid receptor activity is mediated through Stat5, which physically associates with retinoic acid receptors in an IL-3-dependent manner.

The regulation of hematopoiesis involves the interaction of specific hematopoietic cytokines with lineage-specific transcription factors, but little is known about how these cytokines might regulate the expression/activity of these different transcription factors. Here we identify the critical signal transduction pathways that mediate the interleukin 3 (IL-3)-induced enhancement of retinoic acid receptor (RAR) transcriptional activity that accompanies the IL-3-mediated commitment of the multipotent, stem cell factor (SCF)-dependent EML cell line to granulocyte/monocyte progenitors. We observe that the addition of IL-3 to EML cells induces activation of the phosphatidylinositol-3 kinase, mitogen-activated protein kinase, and Jak/Stat pathways and that Jak2 activation is the critical "proximal" mediator of the IL-3-induced enhancement of RAR activity. Constitutively active Stat5 constructs enhance both the transcriptional activity of RARs in EML cells and the commitment of these cells to granulocyte/monocyte progenitors, whereas dominant-negative Stat5 constructs inhibit this IL-3-induced enhancement of RAR transcriptional activity. We observe that the retinoic acid response element (RARE) used in our RA responsive reporter harbors overlapping Stat/RAR-binding sites. Moreover, coimmunoprecipitation studies indicate an interaction between Stat5 and RARs that is IL-3 dependent. Thus, Stat5 is an important mediator of the IL-3-induced enhancement of RAR transcriptional activity that accompanies the commitment of immature EML cells to the granulocyte/monocyte lineage. Cytokine-mediated physical and functional interactions between Stat5 and RARs may play critical roles in regulating different stages of hematopoiesis.

Animals↗
PubMed2003

Plasticity of marrow-derived stem cells.

Bone marrow (BM) contains hematopoietic stem cells (HSCs), which differentiate into every type of mature blood cell; endothelial cell progenitors; and marrow stromal cells, also called mesenchymal stem cells (MSCs), which can differentiate into mature cells of multiple mesenchymal tissues including fat, bone, and cartilage. Recent findings indicate that adult BM also contains cells that can differentiate into additional mature, nonhematopoietic cells of multiple tissues including epithelial cells of the liver, kidney, lung, skin, gastrointestinal (GI) tract, and myocytes of heart and skeletal muscle. Experimental results obtained in vitro and in vivo are the subject of this review. The emphasis is on how these experiments were performed and under what conditions differentiation from bone marrow to epithelial and neural cells occurs. Questions arise regarding whether tissue injury is necessary for this differentiation and the mechanisms by which it occurs. We also consider which bone marrow subpopulations are capable of this differentiation. Only after we have a better understanding of the mechanisms involved and of the cells required for this differentiation will we be able to fully harness adult stem cell plasticity for clinical purposes.

Animals↗
PubMed2006

Nonhematopoietic/endothelial SSEA-1+ cells define the most primitive progenitors in the adult murine bone marrow mesenchymal compartment.

It is believed that a primitive cell type that maintains the mesenchymal compartment exists in the bone marrow. However, this putative mesenchymal stem/progenitor cell is yet to be identified and isolated. We are reporting the identification, isolation, and detailed characterization of the most primitive mesenchymal progenitor cells in the adult murine bone marrow, based on the expression of stage-specific embryonic antigen-1 (SSEA-1). This primitive subset can be identified in mesenchymal cell cultures and also directly in the bone marrow, thus ascertaining for the first time their existence in an adult organism. Characterization of SSEA-1+ mesenchymal cells revealed that upon purification these cells gave rise to SSEA-1- mesenchymal cells, whereas the reverse could not be observed. Also, these SSEA-1+ cells have a much higher capacity to differentiate than their negative counterparts, not only to several mesenchymal cell types but also to unconventional cell types such as astrocyte-, endothelial-, and hepatocyte-like cells in vitro. Most importantly, a single-cell-derived population was capable of differentiating abundantly into different mesenchymal cell types in vivo. Altogether we are proposing a hierarchical organization of the mesenchymal compartment, placing SSEA-1+ cells at the apex of this hierarchy.

Animals↗
PubMed2001

Tramtrack controls glial number and identity in the Drosophila embryonic CNS.

Neurons and glia are often derived from common multipotent stem cells. In Drosophila, neural identity appears to be the default fate of these precursors. Stem cells that generate either neurons or glia transiently express neural stem cell-specific markers. Further development as glia requires the activation of glial-specific regulators. However, this must be accompanied by simultaneous repression of the alternate neural fate. I show that the Drosophila transcriptional repressor Tramtrack is a key repressor of neuronal fates. It is expressed at high levels in all mature glia of the embryonic central nervous system. Analysis of the temporal profile of Tramtrack expression in glia shows that it follows that of existing glial markers. When expressed ectopically before neural stem cell formation, Tramtrack represses the neural stem cell-specific genes asense and deadpan. Surprisingly, Tramtrack protein levels oscillate in a cell cycle-dependent manner in proliferating glia, with expression dropping before replication, but re-initiating after S phase. Overexpression of Tramtrack blocks glial development by inhibiting S-phase and repressing expression of the S-phase cyclin, cyclin E. Conversely, in tramtrack mutant embryos, glia are disrupted and undergo additional rounds of replication. I propose that Tramtrack ensures stable mature glial identity by both repressing neuroblast-specific genes and controlling glial cell proliferation.

Animals↗
PubMed2006

The use of adult stem cells in rebuilding the human face.

BACKGROUND: Stem cells have been isolated from a variety of embryonic and postnatal (adult) tissues, including bone marrow. Bone marrow stromal cells (BMSCs), which are non-blood-forming cells in marrow, contain a subset of skeletal stem cells (SSCs) that are able to regenerate all types of skeletal tissue: bone, cartilage, blood-supportive stromal cells and marrow fat cells. METHODS: Bone marrow suspensions are placed into culture for analysis of their biological character and for expansion of their number. The resulting populations of cells are used in a variety of assays to establish the existence of an adult SSC, and the ability of BMSC populations to regenerate hard tissues in the craniofacial region, in conjunction with appropriate scaffolds. RESULTS: Single-cell analysis established the existence of a true adult SSC in bone marrow. Populations of ex vivo expanded BMSCs (a subset of which are SSCs) are able to regenerate a bone/marrow organ. In conjunction with appropriate scaffolds, these cells can be used to regenerate bone in a variety of applications. CONCLUSIONS: BMSCs have the potential to re-create tissues of the craniofacial region to restore normal structure and function in reconstructing the hard tissues of a face. Ex vivo expanded BMSCs with scaffolds have been used in a limited number of patients to date, but likely will be used more extensively in the near future.

Adult↗
PubMed2005

Regulation and function of neurogenesis in the adult vertebrate brain.

Most adult tissues retain a reservoir of self-renewing, multipotent stem cells that can generate differentiated tissue components. Until recently, the brain was thought to be an exception to this rule and for many years the pervasive dogma of neurobiology relegated neurogenesis to the embryonic and earlier postnatal stages of development. The discovery of constant neuronal replacement in the adult brain has changed the way we think about neurological diseases and about the exploration of new strategies for brain repair. In this review we will explore the potential of adult neural stem cells and we will present some of our own work on this subject. We will also discuss the possibility that adult neurogenesis and neuronal replacement may also play a role in therapies aimed at restoring impaired brain function. A better understanding of the various aspects of spontaneous neuronal replacement may also be used to increase the success of procedures with cell therapies.

Animals↗
PubMed2005

Human bone marrow mesenchymal stem cells can express insulin and key transcription factors of the endocrine pancreas developmental pathway upon genetic and/or microenvironmental manipulation in vitro.

Multipotential stem cells can be selected from the bone marrow by plastic adhesion, expanded, and cultured. They are able to differentiate not only into multiple cell types, including cartilage, bone, adipose and fibrous tissues, and myelosupportive stroma, but also into mesodermal (endothelium), neuroectodermal, or endodermal (hepatocytes) lineages. Our goal was to characterize the multipotential capacities of human mesenchymal stem cells (hMSCs) and to evaluate their ability to differentiate into insulin-secreting cells in vitro. hMSCs were obtained from healthy donors, selected by plastic adhesion, and phenotyped by fluorescence-activated cell sorter and reverse transcription-polymerase chain reaction analysis before and after infection with adenoviruses coding for mouse IPF1, HLXB9, and FOXA2 transcription factors involved early in the endocrine developmental pathway. We found that native hMSCs have a pluripotent phenotype (OCT4 expression and high telomere length) and constitutively express NKX6-1 at a low level but lack all other transcription factors implicated in beta-cell differentiation. In all hMSCs, we detected mRNA of cytokeratin 18 and 19, epithelial markers present in pancreatic ductal cells, whereas proconvertase 1/3 mRNA expression was detected only in some hMSCs. Ectopic expression of IPF1, HLXB9, and FOXA2 with or without islet coculture or islet-conditioned medium results in insulin gene expression. In conclusion, our results demonstrated that in vitro human bone marrow stem cells are able to differentiate into insulin-expressing cells by a mechanism involving several transcription factors of the beta-cell developmental pathway when cultured in an appropriate microenvironment.

Adenoviridae↗
PubMed2005

The involvement of multipotential progenitor cells in Mooren's ulcer.

The aim of this study was to assess the involvement of multipotential progenitor cells in the pathogenesis of Mooren's ulcer using immunohistochemical staining techniques. Tissue specimens were collected from 3 Mooren's ulcer patients who underwent lamellar keratectomy. Immunohistochemical staining patterns were analyzed using antibodies: CD34, c-kit, STRO-1, CD45RO, VEGF and a-SMA. Strong positive CD34, c-kit and STRO-1 cells were revealed in Mooren's ulcer specimens, especially in the superficial stroma. A few weakly expressed CD34 stroma cells were seen in normal limbal cornea but no immunoreactivity for c-kit and STRO-1 could be found. CD45RO positive T cells were found to have infiltrated in Mooren's ulcer. The immunostaining pattern of VEGF and a- SMA was closely correlated with the degree of expression and the number of CD34 positive cells. Bone marrow-derived multipotential progenitor cells may be involved in the pathogenesis of Mooren's ulcer by synergizing with other factors to amplify autoimmune destructive reactions and to contribute to the regeneration process. Specific therapeutic strategies that target the role of these cells in the disease are warranted.

Cornea↗
PubMed2003

Evidence for transdifferentiation of human bone marrow-derived stem cells: recent progress and controversies.

Adult bone marrow-derived stem cells have traditionally been known as tissue-specific stem cells capable of producing blood cells. This concept is being challenged by a series of recent discoveries. It has been demonstrated that there are heterogeneous stem cell populations in adult bone marrow compartment. Under appropriate experimental conditions, a certain type of bone marrow stem cells appears to differentiate (or transdifferentiate) into a variety of non-haemopoietic cells of ectodermal, mesodermal and endodermal origins (such as myocytes, neural cells and hepatocytes). The plasticity, that is, the ability to regenerate cells belonging to different organs and tissues of adult (postnatal) stem cells, has raised the therapeutic possibility of using these stem cells for tissue repair and regeneration. Presently, definitive evidence for plasticity or transdifferentiation of bone marrow stem cells is lacking. Despite controversies concerning the plasticity of bone marrow-derived stem cells, early clinical trials are being conducted in patients suffering from myocardial infarct, arthritic and neurological diseases using autologous bone marrow stem cells. This review summarises recent progresses and controversies in transdifferentiation of adult bone marrow-derived stem cells to non-haemopoietic tissues.

Adult↗
PubMed2004

[Influence of ganciclovir and astragalus membranaceus on proliferation of hematopoietic progenitor cells of cord blood after cytomegalovirus infection in vitro].

OBJECTIVE: Cytomegalovirus (CMV) infection was greatly common in the world. CMV infection produces usually mild or asymptomatic infections in individuals with normal immune responses, whereas it may cause serious disease in immunosuppressive patients. Clinical manifestations include suppression of myelopoiesis, a mononucleosis like syndrome, hepatosplenomegaly, lymphadenopathy, thrombocytopenia, and hemolytic anemia. In patients undergoing bone marrow transplantation CMV remains the most common infectious causes of morbidity and mortality. But the treatment drugs with specific effect for CMV was fewer at the present. This study was to investigate the effect of CMV on proliferation of colony forming unit granulocyte-macrophage (CFU-GM), CFU-erythroid (CFU-E), brust forming unit-erythroid (BFU-E), CFU-multipotential (CFU-Mix) and CFU-megakaryocyte (CFU-Mk) progenitor cells of cord blood (CB) with the presence of ganciclovir (GCV) and astragalus membranaceus in vitro. METHODS: Twenty CB samples were collected from fetal umbilical vein of normal term spontaneous delivery neonates. The colony forming unit-assay was applied to observe the suppression effect of CMV-AD169 strain on CFU-GM, CFU-E, BFU-E, CFU-Mix and CFU-Mk of CB with the presence of GCV and astragalus membranaceus in vitro. The technique of PCR was used to demonstrate the existence of CMV-AD169 DNA in the colony cells of cultured CFU-GM, CFU-E, BFU-E, CFU-Mix and CFU-Mk. RESULTS: (1) The numbers of CFU-GM, CFU-E, BFU-E, CFU-Mix and CFU-Mk colonies in CMV infection groups were significantly less than those in blank and mock group, respectively. The last time of colonies in groups with CMV infection was significantly shorten compared with the blank and mock group. (2) CMV-DNA was positively detected in the colony cells of CMV infection groups by PCR, while negative in the control groups. (3) The lasting time of CFU-GM, CFU-E, BFU-E, CFU-Mix and CFU-Mk colonies infected with CMV extended significantly with the presence of astragalus membranaceus and GCV, and the numbers of those increased significantly compared with the CMV infection group, respectively. The increasing rate of colonies was 27.2%, 45.2%, 49.1%, 39.0% and 11.9% with astragalus membranaceus group, 37.4%, 74.2%, 71.7%, 67.4% and 38.9% with GCV group, 53.6%, 83.8%, 88.7%, 87.8% and 61.5% with astragalus membranaceus and GCV group, respectively. CONCLUSIONS: The differentiation and proliferation of CFU-GM, CFU-E, BFU-E, CFU-Mix and CFU-Mk were significantly inhibited after infected with CMV-AD169 strain. The suppression effect of CMV-AD169 on CFU-GM, CFU-E, BFU-E, CFU-Mix and CFU-Mk was inhibited with the presence of GCV and astragalus membranaceus in vitro. This suggested that CMV-AD169 may be inhibited or killed by GCV and Astragalus Membranaceus in vitro.

Antiviral Agents↗
PubMed2005

Adipose-derived mesenchymal cells as a potential cell source for skeletal regeneration.

Recent studies suggest that adipose tissue contains pluripotent cells that are similar to those derived from other tissues, such as bone marrow. Mesenchymal cells isolated from adipose tissue are capable of differentiating along osteogenic, chondrogenic, myogenic, adipogenic and possibly neuronal lineages. Current knowledge of adipose-derived mesenchymal cells is reviewed, with a particular focus on efforts to direct these cells towards bone formation. Cell-based therapies using adipose tissue are anticipated to be of great clinical interest for skeletal tissue repair and regeneration.

Adipose Tissue↗