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Arterioscler Thromb Vasc Biol. 2008 Dec;28(12):2137-43. doi: 10.1161/ATVBAHA.108.168815. Epub 2008 Sep 25.

Bone morphogenetic proteins 2 and 4 are selectively expressed by late outgrowth endothelial progenitor cells and promote neoangiogenesis.

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  • 1Université Paris Descartes, Faculté de Pharmacie, INSERM UMRS 765, 4 Avenue de l'observatoire, F-75006 Paris, France.

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.

PMID:
18818419
[PubMed - indexed for MEDLINE]
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