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 3

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Differentiation into endothelial cells requires absence of serum and hig...
Differentiation into endothelial cells requires absence of serum and high density of MAPCs. (a) MAPCs (after 65 population doublings; donor age, 22 years) were replated at 2 × 104 cells/cm2 in fibronectin-coated wells in serum-free medium with 10 ng/ml VEGF in the presence or absence of serum (2% FCS). After 9 days, cells were fixed with paraformaldehyde, permeabilized with Triton X-100, and stained with Ab’s against vWF and CD34. Representative example of three experiments, one from each of three different donors. (b) MAPCs (after 65 population doublings; donor age, 22 years) were replated at 2 × 104 cells/cm2 or ≤ 1 × 104 cells/cm2 in fibronectin-coated wells in serum-free defined medium with 10 ng/ml VEGF. After 9 days, cells were fixed with paraformaldehyde, permeabilized with Triton X-100, and stained with Ab’s against vWF and CD34. Representative example of three experiments from three donors. (c) MAPCs (after 45 population doublings; donor age, 28 years) were replated at 2 × 104 cells/cm2 in fibronectin-coated wells in serum-free defined medium with 10 ng/ml VEGF. After 9 days, endothelial cells were further expanded in 10% FCS with 10 ng/ml VEGF for more than 20 population doublings. Representative example of six experiments from six donors.