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Results for “Multipotent Stem Cells”

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At least 433 records · Page 24Linked to original sources

PubMed2005

Derivation of multipotent mesenchymal precursors from human embryonic stem cells.

BACKGROUND: Human embryonic stem cells provide access to the earliest stages of human development and may serve as a source of specialized cells for regenerative medicine. Thus, it becomes crucial to develop protocols for the directed differentiation of embryonic stem cells into tissue-restricted precursors. METHODS AND FINDINGS: Here, we present culture conditions for the derivation of unlimited numbers of pure mesenchymal precursors from human embryonic stem cells and demonstrate multilineage differentiation into fat, cartilage, bone, and skeletal muscle cells. CONCLUSION: Our findings will help to elucidate the mechanism of mesoderm specification during embryonic stem cell differentiation and provide a platform to efficiently generate specialized human mesenchymal cell types for future clinical applications.

Adipocytes↗

PubMed2002

[Culture and pluripotentiality of human marrow mesenchymal stem cells].

OBJECTIVE: To cultivate human mesenchymal stem cells (MSC) derived from fetal bone marrow and examine their pluripotentiality. METHODS: Bone marrow mononuclear cells from human fetal femur were collected by Percoll gradient centrifugation. The low density cells including MSCs were cultivated and expanded in MSCGM media. The characteristics of the multipotent MSCs were observed by implanting them into nude mice for 4 weeks. RESULTS: Human fetal marrow MSCs were successfully cultivated and differentiated in vivo into many kinds of tissues such as bone, cartilage, adipose, skeletal muscle and tendon-like tissue. CONCLUSION: Human fetal marrow MSCs were multipotent stem cells.

Animals↗

PubMed2005

Cellular and molecular control of neurogenesis in the mammalian telencephalon.

The mammalian telencephalon exhibits an amazing diversity of neuronal types. The generation of this diversity relies on multiple developmental strategies, including the regional patterning of progenitors, their temporal specification, and the generation of intermediate progenitor populations. Progress has recently been made in characterizing some of the mechanisms involved. In particular, intermediate progenitors have been shown to play important roles in the generation of neurons in the cerebral cortex, and the properties and lineage relationships between radial glial cells and these intermediate progenitors have recently been examined by elegant time-lapse microscopic studies. Multiple pathways control the progression of neural lineages from multipotent stem cells to intermediate progenitors, postmitotic precursors and finally mature neurons. The regulation of two essential steps, neuronal commitment and specification of subtype identities, is increasingly well understood. These two steps are clearly distinct but co-ordinately regulated by common transcription factors such as neurogenins and Pax6. As our knowledge of the mechanisms of subtype specification of telencephalic neurons progresses, it will become possible to direct stem cells into generating particular telencephalic neuronal populations, opening the way to efficient neuronal replacement therapies.

Animals↗

PubMed1983

Essential thrombocythemia: a clonal disorder of hematopoietic stem cell.

We studied 5 patients with essential thrombocythemia utilizing glucose-6-phosphate dehydrogenase (G-6-PD) enzyme as a cell marker for determining clonality. One of the patients was found to be heterozygous for isoenzymes B and A in the nonhaemopoietic tissues such as fibroblasts, but manifested only isoenzyme type B in the erythrocytes, neutrophils, and platelets. Our studies support the concept that essential thrombocythemia is a clonal disorder arising in a multipotent stem cell.

Blood Platelets↗

PubMed1988

The role of ultrastructural cytochemistry and monoclonal antibodies in clarifying the nature of undifferentiated cells in acute leukaemia.

The nature of the cells in 21 cases of acute leukaemia with blasts which were undifferentiated by light microscopy criteria was investigated by immunophenotyping, ultrastructural cytochemistry and DNA analysis. Two groups of cases were recognized. Fourteen cases were negative with B and T lymphoid markers and expressed one or two myeloid antigens detected by the monoclonal antibodies (McAb) MCS2 (CD13) and MY9 (CD33). Peroxidase activity was demonstrated at ultrastructural level by the method of Roels on unfixed cells in eight out of 10 cases; rearrangement of the immunoglobulin (Ig) genes was demonstrated in one of the three cases investigated. These cases are proliferations of early, MO, myeloblasts which can only be recognized by immunological and ultrastructural cytochemical methods. The remaining seven cases revealed a complex phenotype with expression of myeloid and lymphoid antigens. Peroxidase activity was detected in blasts from two cases with rearrangement of the Ig-heavy chain gene; in one of them the T cell receptor beta and gamma chain genes were also found in rearranged configuration. This group comprises cases of biphenotypic and mixed acute leukaemia which probably involve multipotent stem cells. This study demonstrates that the expression of myeloid antigens on blast cells parallels closely the presence of peroxidase activity and that lymphoid markers correlate with gene rearrangements at DNA level. Our findings are reassuring with respect to the specificity of the antimyeloid McAb for the diagnosis of cases which are unclassifiable by conventional methods.

Acute Disease↗

PubMed1995

Glycosylphosphatidylinositol (GPI)-anchored membrane proteins in clinical pathophysiology of paroxysmal nocturnal hemoglobinuria (PNH).

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hemolytic anemia in which abnormal red blood cells with enhanced susceptibility to complement undergo intravascular hemolysis when complement is activated in vivo, resulting in hemoglobinuria. This enhancement of complement susceptibility appears to involve multipotent stem cells and, in this respect, is thought to closely resemble myelodysplastic syndrome. Recently, it has been reported that the increased susceptibility of PNH cells to complement-mediated lysis is related to a deficiency of complement regulatory membrane proteins, especially CD55 and CD59. Both proteins are glycosylphosphatidylinositol (GPI)-anchored membrane proteins. It was found that a deficiency of GPI-anchored membrane proteins in PNH cells is due to the faulty synthesis of the GPI-anchor which may occur during early synthesis. Moreover, it is suggested that an abnormality of the PIG-A (phosphatidylinositol glycan-class A) gene, which is related to the early stage of GPI-anchor synthesis, is responsible for the pathogenesis of PNH. In conclusion, the clinical expression of PNH is dependent on two factors, complement susceptibility of PNH blood cells and changes in bone marrow function. The search for the ideal treatment of this disease may be aided by resolving the relationship between the two.

Complement Activation↗

PubMed2002

Molecular characterization of mouse gastric epithelial progenitor cells.

The adult mouse gastric epithelium undergoes continuous renewal in discrete anatomic units. Lineage tracing studies have previously disclosed the morphologic features of gastric epithelial lineage progenitors (GEPs), including those of the presumptive multipotent stem cell. However, their molecular features have not been defined. Here, we present the results of an analysis of genes and pathways expressed in these cells. One hundred forty-seven transcripts enriched in GEPs were identified using an approach that did not require physical disruption of the stem cell niche. Real-time quantitative RT-PCR studies of laser capture microdissected cells retrieved from this niche confirmed enriched expression of a selected set of genes from the GEP list. An algorithm that allows quantitative comparisons of the functional relatedness of automatically annotated expression profiles showed that the GEP profile is similar to a dataset of genes that defines mouse hematopoietic stem cells, and distinct from the profiles of two differentiated GEP descendant lineages (parietal and zymogenic cell). Overall, our analysis revealed that growth factor response pathways are prominent in GEPs, with insulin-like growth factor appearing to play a key role. A substantial fraction of GEP transcripts encode products required for mRNA processing and cytoplasmic localization, including numerous homologs of Drosophila genes (e.g., Y14, staufen, mago nashi) needed for axis formation during oogenesis. mRNA targeting proteins may help these epithelial progenitors establish differential communications with neighboring cells in their niche.

Adenosine Triphosphate↗

PubMed2000

Complex organization in multicellularity as a necessity in evolution.

By introducing a dynamical system model of a multicellular system, it is shown that an organism with a variety of differentiated cell types and a complex pattern emerges through cell-cell interactions even without postulating any elaborate control mechanism. Such an organism is found to maintain a larger growth speed as an ensemble, by achieving a cooperative use of resources, than do simple homogeneous cells, which behave "selfishly." This suggests that the emergence of multicellular organisms with complex organization is a necessity in evolution. According to our theoretical model, there initially appear multipotent stem cells, which undergo stochastic differentiation to other cell types. With development and differentiation, both the chemical diversity and the complexity of intra-cellular dynamics are decreased, as a general consequence of our system. Robustness of the developmental process is also confirmed.

Biological Evolution↗

PubMed1984

Segregation and characterization of lymphohematopoietic stromal elements.

In the mouse, long-term maintenance of multipotent hematopoietic stem cells in vitro currently requires the establishment of an appropriate adherent layer. When established employing culture medium supplemented with 20% horse serum and 10(-6) M hydrocortisone, the initial adherent layer contains primitive stem cells that are the major contributor of multipotent stem cells (CFUs) assayed subsequently in the supernatant regardless of the addition of fresh bone marrow cells. In contrast, when the adherent layer is established employing 25% fetal calf serum without hydrocortisone, few if any stem cells survive in the adherent layer. Such cultures are dependent upon a recharge with fresh bone marrow as a source of CFUs. A comparison of the latter stem cell-depleted system with the former intact system permits an evaluation of the relative contributions of the adherent layer and stem cells to the long-term maintenance of hematopoiesis in vitro. Studies of the effects of irradiation of the donor animal for the adherent layer and using the intact system demonstrated a reduction in the supernatant CFUs production that was dose- and time-related and evident at doses of 100 and 500 rads. If the adherent layer itself was irradiated immediately before refeeding, a reduction in supernatant CFUs was evident at a dose of 5 rads. These effects, both in vivo and in vitro, cannot be explained solely on the basis of cell killing. Rather, we propose that such doses inactivate, render impotent, or reduce the self-renewal capacity of stem cells that occupy a limited number of "niches" in the adherent layer. Although they are not killed, these impotent stem cells occupy stem cell niches but do not provide an effective contribution of CFUs to the supernatant cells. The adherent layer consists primarily of fibroblasts with significant numbers of macrophages and endothelial cells. The cellular composition of the adherent layer differs between the intact and stem cell-depleted systems in that the latter has a relatively larger proportion of endothelial cells. The composition of the adherent layer influences the type of differentiated cells in the supernatant. The stem cell-depleted adherent layer cultures had a greater proportion of granulocytes among the supernatant cells than macrophages that eventually predominate in the intact system. We have cloned stromal cells from the intact cultures and obtained several stromal cell lines by spontaneous transformation. One of these stromal cell lines (MC1) transfers at least a partial hematopoietic "microenvironment" (granulocytes, macrophages, erythroid cells) to ectopic sites on transplantation to syngeneic recipients.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1986

A variant of the congenital dyserythropoietic anaemia type II with structural abnormalities in the granulocytic series.

Typical features of congenital dyserythropoietic anaemia (CDA) were found in a 13-year-old girl admitted for chronic recurrent multifocal osteomyelitis. The findings on light microscopy were in agreement with those described in CDA type II, whereas on electron microscopy, the ultrastructure findings were compatible with both types I and II. The acidified serum lysis test (Ham test) performed with eight normal sera was negative. The patient's red blood cells showed an increased agglutinability with anti-i antibodies. Morphological changes were also shown in the mature neutrophilic granulocyte suggesting that the primary disorder exists already in the multipotent stem cell.

Adolescent↗

PubMed2005

Conditional telomerase induction causes proliferation of hair follicle stem cells.

TERT, the protein component of telomerase, serves to maintain telomere function through the de novo addition of telomere repeats to chromosome ends, and is reactivated in 90% of human cancers. In normal tissues, TERT is expressed in stem cells and in progenitor cells, but its role in these compartments is not fully understood. Here we show that conditional transgenic induction of TERT in mouse skin epithelium causes a rapid transition from telogen (the resting phase of the hair follicle cycle) to anagen (the active phase), thereby facilitating robust hair growth. TERT overexpression promotes this developmental transition by causing proliferation of quiescent, multipotent stem cells in the hair follicle bulge region. This new function for TERT does not require the telomerase RNA component, which encodes the template for telomere addition, and therefore operates through a mechanism independent of its activity in synthesizing telomere repeats. These data indicate that, in addition to its established role in extending telomeres, TERT can promote proliferation of resting stem cells through a non-canonical pathway.

Animals↗

PubMed1996

[Polycythemia vera progressing to acute lymphoblastic leukemia after 13 years].

A 54-year-old woman with leukocytosis, was referred to our clinic in February 1982. Based on findings of pancytosis, high NAP score, high serum vitamin B12, increase in total red cell volume and splenomegaly, she was diagnosed as having polycythemia vera (PV). Since then, she has been treated with pipobroman, hydroxycarbamide and phlebotomy. Leukocytosis with increase in blastic cells and thrombocytopenia was noted in August 1995, and she was admitted to our hospital. Since the blastic cells were CD10(+)19(+)20(+), she was diagnosed as having acute lymphoblastic leukemia and treated with vincristine and prednisolone, resulting in remission. This case suggests that PV is a disease of multipotent stem cells including those with a lymphoid lineage.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2006

In vitro differentiation of human placenta-derived multipotent cells into hepatocyte-like cells.

Multipotent cells isolated from human term placenta (placenta-derived multipotent cells [PDMCs]) have been known to be able to differentiate into mesodermal lineage cells, including adipocytes and osteoclasts. The low infection rate and young age of placenta compared with other tissue origins of adult stem cells make theses cells attractive target for cell-based therapy. However, the differentiation potential of PDMCs toward hepatic cells has not been evaluated yet. In this study, we cultivated PDMCs with hepatic differentiation medium to evaluate the ability of these cells in differentiating toward hepatic cells. After treatment, the morphologies of differentiated PDMCs changed to polygonal epithelial cell-like. The differentiated cells not only show the hepatocyte-like morphologies but also express hepatocyte-specific markers, including albumin and cytokeratin 18. The bioactivity assays revealed that these hepatocyte-like cells could uptake lipoprotein and store glycogen. Furthermore, the addition of rifampicin increased the gene expression of CYP3A4, which is similar with the activities of human liver cells. According to our previous results, PDMCs were capable of differentiating into mesodermal and ectodermal lineage cells. Our results indicate that PDMCs can differentiate into three germ layer cells, which is similar to embryonic stem cells. In conclusion, placenta might be an easily accessible source for progenitor cells that are capable of differentiating toward hepatocyte-like cells in vitro.

Albumins↗

PubMed2002

Changes in the proteome associated with the action of Bcr-Abl tyrosine kinase are not related to transcriptional regulation.

Chronic myeloid leukemia (CML) is a hematopoietic stem cell disease, the hallmark of which is the Bcr-Abl protein tyrosine kinase (PTK). Without intervention the disease progresses from a benign chronic phase to a rapidly fatal blast crisis. To identify the molecular mechanisms underlying disease progression we used two-dimensional gel electrophoresis on a model we have previously described using the expression of a conditional mutant of Bcr-Abl PTK in a multipotent stem cell line, FDCP-Mix. Long term exposure of FDCP-Mix cells to Bcr-Abl mimics disease progression in CML. Four major differences were observed as a consequence of long term exposure to the Bcr-Abl PTK compared with cells exposed short term. The proteins were identified using matrix-assisted laser desorption ionization-time of flight mass spectrometry-generated peptide mass fingerprint data and liquid chromatography-tandem mass spectrometry-generated sequence information. Leukotriene A4 hydrolase, an enzyme known to be deregulated in CML, was found to be up-regulated. Annexin VI, vacuolar ATP synthase catalytic subunit A, and mortalin were found to be down-regulated. Poly(A) PCR cDNA analysis showed there was no correlation between the protein expression changes and mRNA levels. Western blot analysis also indicated no change in the levels of mortalin or leukotriene A4 hydrolase, indicating that post-translational events may modify protein content of the specific spots. Leukotriene B4 levels (product of leukotriene A4 hydrolase) were, however, reduced in cells exposed long term to Bcr-Abl activity. This study demonstrates the potential of proteomic analysis to define novel effects of oncogenes.

Animals↗

PubMed1987

Facilitation of allogeneic bone marrow transplantation by a T cell-specific immunotoxin containing daunomycin.

Daunomycin coupled via an acid-sensitive spacer to monoclonal Thy-1.2-specific antibody was used to purge T lymphocytes from a 1:1 mixture of murine C57BL/6J bone marrow and spleen cells prior to engraftment in fully allogeneic, irradiated BALB/c recipients. Treatment of bone marrow with the immunotoxin at a concentration used for purging had no effect on the viability of committed hematopoietic progenitor or multipotent stem cells. All of the recipients of purged bone marrow were at least 80% chimeric for donor peripheral blood cells and none developed graft-versus-host disease. Out of 50 chimeras, 49 were still alive more than 200 days posttransplantation. The chimeras were shown to be tolerant to donor tissue as tested by mixed lymphocyte reactivity, cell-mediated cytotoxicity, and skin grafting. The same tests revealed full immunocompetence of chimeras to third-party alloantigens. In vivo IgM and IgG antibody responses to sheep red blood cells were similar in magnitude in allogeneically and syngeneically reconstituted mice.

Animals↗

PubMed1988

Multipotent hemopoietic progenitor cells in patients with systemic lupus erythematosus.

Hematologic abnormalities in patients with systemic lupus erythematosus (SLE) were studied before treatment, using an in vitro bone marrow progenitor cell assay. In 10 patients with SLE, there was a decrease in the number of multipotent hemopoietic colonies. Multipotent colony formation was suppressed by the addition of T cells from the patients with SLE. The culture supernatant of phytohemagglutinin stimulated SLE leukocytes had diminished activity to support the multipotent colony formation. These results suggest that the hematologic abnormalities in SLE occur at the multipotent stem cell level. The T cell mediated suppression of hemopoietic progenitor cells and the diminished activity of humoral factors released from SLE leukocytes may play some role in the pathogenesis of hematologic abnormalities in SLE.

Bone Marrow↗

PubMed2005

Mll fusions generated by Cre-loxP-mediated de novo translocations can induce lineage reassignment in tumorigenesis.

Chromosomal translocations are primary events in tumorigenesis. Those involving the mixed lineage leukaemia (MLL) gene are found in various guises and it is unclear whether MLL fusions can affect haematopoietic differentiation. We have used a model in which chromosomal translocations are generated in mice de novo by Cre-loxP-mediated recombination (translocator mice) to compare the functionally relevant haematopoietic cell contexts for Mll fusions, namely pluripotent stem cells, semicommitted progenitors or committed cells. Translocations between Mll and Enl or Af9 cause myeloid neoplasias, initiating in pluripotent stem cells or multipotent myeloid progenitors. However, while Mll-Enl translocations can also cause leukaemia from T-cell progenitors, no tumours arose with Mll-Af9 translocations in the T-cell compartment. Furthermore, Mll-Enl translocations in T-cell progenitors can cause lineage reassignment into myeloid tumours. Therefore, a permissive cellular environment is required for oncogenicity of Mll-associated translocations and Mll fusions can influence haematopoietic lineage commitment.

Animals↗

PubMed1991

[Myelodysplastic syndrome with neoplastic angioendotheliosis: report of a case].

A 62-year-old woman was admitted to our hospital because of general malaise in May, 1987. No hepatosplenomegary, skin eruption or lymphadenopathy was detected. Laboratory examinations showed mild anemia, thrombocytopenia, normal leukocyte count with no lymphocyte abnormality, hypogranular neutrophils, elevated serum lactic dehydrogenase, increased C-reactive protein and hypoxia. Bone marrow aspirate was normocellular with dysplastic changes in erythroid and megakaryocytic lines which agree with a diagnosis of myelodysplastic syndrome (MDS). She was treated with prednisolone which relieved her symptom but she developed high fever, hemiplegia and disturbance of consciousness and died in August, 1987. Necropsy of the kidney revealed large mononuclear cells within the lumen of small blood vessels. Immunohistochemical study of these malignant cells showed positive reaction to the anti-LCA and anti-L26 antibodies. And electron microscopy showed no azure granules in these cells. Then we diagnosed as neoplastic angioendotheliosis (NAE). To our knowledge, this is the first report of NAE with abnormalities in myeloid, erythroid and megakaryocytic lineages. These results suggest that NAE with MDS originate from a multipotent stem cell.

Female↗