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  • 1
    Publication Date: 2001-04-01
    Description: It is shown that the tetraspanin CD9 has a complex pattern of distribution in hematopoietic cells and is heterogeneously expressed on human bone marrow CD34+ cells. CD34highCD38lowThy1+ primitive progenitors are contained in the population with intermediate CD9 expression, thus suggesting that CD9 expression may precede CD38 appearance. Cell sorting shows that colony-forming unit (CFU)-GEMM and CFU-GM are present in high proportions in this fraction and in the fraction with the lowest CD9 expression. Cells with the highest level of CD9 are committed to the B-lymphoid or megakaryocytic (MK) lineages, as shown by the co-expression of either CD19 or CD41/GPIIb and by their strong potential to give rise to CFU-MK. In liquid cultures, CD9highCD41neg cells give rise to cells with high CD41 expression as early as 2 days, and this was delayed by at least 3 to 4 days for the CD9mid cells; few CD41high cells could be detected in the CD9lowcell culture, even after 6 days. Antibody ligation of cell surface CD9 increased the number of human CFU-MK progenitors and reduced the production of CD41+ megakaryocytic cells in liquid culture. This was associated with a decreased expression of MK differentiation antigens and with an alteration of the membrane structure of MK cells. Altogether these data show a precise regulation of CD9 during hematopoiesis and suggest a role for this molecule in megakaryocytic differentiation, possibly by participation in membrane remodeling.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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  • 2
    Publication Date: 2003-04-15
    Description: Liver becomes the predominant site of hematopoiesis by 11.5 dpc (days after coitus) in the mouse and 15 gestational weeks in humans and stays so until the end of gestation. The reason the liver is the major hematopoietic site during fetal life is not clear. In this work, we tried to define which of the fetal liver microenvironmental cell populations would be associated with the development of hematopoiesis and found that a population of cells with mixed endodermal and mesodermal features corresponded to hematopoietic-supportive fetal liver stroma. Stromal cells generated from primary cultures or stromal lines from mouse or human fetal liver in the hematopoietic florid phase expressed both mesenchymal markers (vimentin, osteopontin, collagen I, α smooth muscle actin, thrombospondin-1, EDa fibronectin, calponin, Stro-1 antigens, myocyte-enhancer factor 2C) and epithelial (α-fetoprotein, cytokeratins 8 and 18, albumin, E-cadherin, hepatocyte nuclear factor 3 α) markers. Such a cell population fits with the description of cells in epithelial-to-mesenchymal transition (EMT), often observed during development, including that of the liver. The hematopoietic supportive capacity of EMT cells was lost after hepatocytic maturation, induced by oncostatin M in the cell line AFT024. EMT cells were observed in the fetal liver microenvironment during the hematopoietic phase but not in nonhematopoietic liver by the end of gestation and in the adult. EMT cells represent a novel stromal cell type that may be generated from hepatic endodermal or mesenchymal stem cells or even from circulating hematopoietic stem cells (HSCs) seeding the liver rudiment.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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  • 3
    Publication Date: 2004-04-01
    Description: Endothelial progenitor cells (EPCs) were shown to be present in systemic circulation and cord blood. We investigated whether EPCs display specific properties compared with mature endothelial cells. Human cord blood CD34+ cells were isolated and adherent cells were amplified under endothelial conditions. Expression of specific markers identified them as endothelial cells, also called endothelial progenitor-derived cells (EPDCs). When compared to mature endothelial cells, human umbilical vein endothelial cells (HUVECs) and human bone marrow endothelial cells (HBMECs), endothelial markers, were expressed to the same extent except for KDR, which is expressed more in EPDCs. They display a higher proliferation potential. Functional studies demonstrated that EPDCs were more sensitive to angiogenic factors, which afford these cells greater protection against cell death compared with HUVECs. Moreover, EPDCs exhibit more hematopoietic supportive activity than HUVECs. Finally, studies in nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice demonstrated that human circulating EPCs are able to colonize a Matrigel plug. EPDCs display the morphology and phenotype of endothelial cells. Their functional features indicate, however, that although these cells have undergone some differentiation steps, they still have the properties of immature cells, suggesting greater tissue repair capabilities. Future use of in vitro amplified peripheral blood EPDCs may constitute a challenging strategy for cell therapy.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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