4.7 Article

Bone Morphogenetic Proteins 2 and 4 Are Selectively Expressed by Late Outgrowth Endothelial Progenitor Cells and Promote Neoangiogenesis

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LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/ATVBAHA.108.168815

关键词

endothelial progenitor cells; bone morphogenetic protein; critical leg ischemia; cell therapy; neovascularization

资金

  1. INSERM
  2. Programme Hospitalier de Recherche Clinique OPTIPEC [PHRC AOM 03 034]
  3. Leducq TransAtlantic Network of Excellence on Atherothrombosis Research [04CVD01]

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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/B16 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. Conclusion - BMP2/4 are a marker of ECFCs and play a key role in ECFC commitment and outgrowth during neovascularization. (Arterioscler Thromb Vasc Biol. 2008;28:2137-2143.)

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