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  • Title: Bone morphogenetic proteins 2 and 4 are selectively expressed by late outgrowth endothelial progenitor cells and promote neoangiogenesis.
    Author: Smadja DM, Bièche I, Silvestre JS, Germain S, Cornet A, Laurendeau I, Duong-Van-Huyen JP, Emmerich J, Vidaud M, Aiach M, Gaussem P.
    Journal: Arterioscler Thromb Vasc Biol; 2008 Dec; 28(12):2137-43. PubMed ID: 18818419.
    Abstract:
    OBJECTIVE: Endothelial progenitor cells are currently identified either by their surface antigen expression or by their generation of early colonies in culture (CFU-Hill). Another population, endothelial colony-forming cells (ECFCs), has strong vessel-forming capacity but is less well characterized. Given the potential usefulness of CFU-Hill and ECFCs as cell therapy products, their thorough characterization is of major importance. METHODS AND RESULTS: CFU-Hill and ECFCs were expanded from human cord and adult blood. Bone morphogenetic proteins 2 and 4 (BMP2/4) were selectively expressed by ECFCs but not by CFU-Hill. The BMP pathway was involved in ECFC commitment and angiogenic potential in vitro. In vivo, BMP inhibition strongly reduced plug vascularization in bFGF-containing Matrigel plugs implanted in C57/Bl6 mice. Moreover, ECFC exposure to BMP increased their therapeutic potential in a nude mouse model of hindlimb ischemia. In amputation specimens from patients with critical leg ischemia who had received a local therapeutic injection of bone marrow mononuclear cells, newly formed vessels were strongly positive for BMP2/4, suggesting that endothelial cells involved in neovascularization have an ECFC-like phenotype. CONCLUSIONS: BMP2/4 are a marker of ECFCs and play a key role in ECFC commitment and outgrowth during neovascularization.
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