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

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 1

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FACS analysis of undifferentiated MAPCs and MAPCs cultured with VEGF. MA...
FACS analysis of undifferentiated MAPCs and MAPCs cultured with VEGF. MAPCs (after 40 population doublings; donor age, 28 years) were replated at 2 × 104 cells/cm2 in fibronectin-coated wells in serum-free defined medium without EGF or PDGF-BB, but with 10 ng/ml VEGF. Undifferentiated MAPCs at day 0, or VEGF-induced cells recovered after short trypsinization after 3, 9, or 14 days of culture, were stained with Ab’s against β2-microglobulin, HLA class I, MUC18, Flk1, Flt1, VCAM, CD62P, CD62E, vWF, CD31, CD34, CD36, AC133, VE-cadherin, or control IgG. Cells were analyzed by FACS. Plots show isotype control IgG staining profile (thin line) versus specific Ab staining profile (thick line). Each analysis shown is one representative example from a total of three donors. Values on x axes indicate intensity log. (a) Phenotype of undifferentiated MAPCs. MAPCs express low levels of β2-microglobulin, Flk1, Flt1, and AC133, but do not stain with any of the other anti-endothelial markers. (b) Phenotype of MAPCs cultured for 14 days with 10 ng/ml VEGF. MAPCs express high levels of most endothelial markers associated with endothelial cells, but lose expression of AC133. (c) Phenotype of MAPCs cultured for 3–9 days with 10 ng/ml VEGF. MAPCs lose expression of AC133 by day 3 of culture with VEGF, and acquire expression of Tek by day 3, and vWF, CD34, and MUC18 by day 9. β2-mic, β2-microglobulin; VE-cad, VE-cadherin.