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Origin of endothelial progenitors in human postnatal bone marrow
Morayma Reyes, … , Paul H. Marker, Catherine M. Verfaillie
Morayma Reyes, … , Paul H. Marker, Catherine M. Verfaillie
Published February 1, 2002
Citation Information: J Clin Invest. 2002;109(3):337-346. https://doi.org/10.1172/JCI14327.
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Article

Origin of endothelial progenitors in human postnatal bone marrow

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Abstract

This study demonstrates that a CD34–, vascular endothelial cadherin– (VE-cadherin–), AC133+, and fetal liver kinase+ (Flk1+) multipotent adult progenitor cell (MAPC) that copurifies with mesenchymal stem cells from postnatal human bone marrow (BM) is a progenitor for angioblasts. In vitro, MAPCs cultured with VEGF differentiate into CD34+, VE-cadherin+, Flk1+ cells — a phenotype that would be expected for angioblasts. They subsequently differentiate into cells that express endothelial markers, function in vitro as mature endothelial cells, and contribute to neoangiogenesis in vivo during tumor angiogenesis and wound healing. This in vitro model of preangioblast-to-endothelium differentiation should prove very useful in studying commitment to the angioblast and beyond. In vivo, MAPCs can differentiate in response to local cues into endothelial cells that contribute to neoangiogenesis in tumors. Because MAPCs can be expanded in culture without obvious senescence for more than 80 population doublings, they may be an important source of endothelial cells for cellular pro- or anti-angiogenic therapies.

Authors

Morayma Reyes, Arkadiusz Dudek, Balkrishna Jahagirdar, Lisa Koodie, Paul H. Marker, Catherine M. Verfaillie

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Figure 5

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Further functional characterization of MAPC-derived endothelial cells. (...
Further functional characterization of MAPC-derived endothelial cells. (a) Hypoxia upregulates Flk1 and Tek expression on MAPC-derived endothelial cells. MAPC-derived endothelial cells (after 30 population doublings; donor age, 33 years) were incubated at 37°C in 20% or 10% O2 for 24 hours. Cells were recovered by trypsinization and stained with Ab’s against Flk 1, Tek, and IgG control, and were analyzed by flow cytometry. Plots show isotype control IgG staining profile (thin line) versus specific Ab staining profile (thick line). Representative example of more than three experiments from three donors. Number above plots shows mean fluorescence intensity (MFI) for the control IgG staining and the specific Ab staining. (b) Hypoxia upregulates VEGF production by MAPC-derived endothelial cells. MAPCs (after 30 population doublings; donor age, 45 years) and MAPC-derived endothelial cells were incubated at 37°C in 20% or 10% O2 for 24 hours. Medium was collected, and VEGF levels were measured by ELISA. Results are shown as mean ± SEM of six experiments from three donors. (c) IL-1α induces expression of HLA-DR, a type of HLAclass II antigens and increases expression of adhesion receptors. MAPC-derived endothelial cells (after 40 population doublings, donor age = 31 years) were incubated with 75 ng/ml IL-1α in serum-free medium for 24 hours. Cells were stained with Ab’s against HLA-class I, HLA class II, β2-microglobulin, vWF, CD31, VCAM, CD62E, CD62P, or control Ab’s, and analyzed using FACS. Plots show isotype control IgG staining profile (thin line) versus specific Ab staining profile (thick line). Representative example of three experiments from three donors. Numbers above each plot show MFI for the control IgG staining and the specific Ab staining. Nl, normal; IL-1 induced populations.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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