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Will endothelial progenitor cells represent a cell therapy product for the treatment of cardiovascular diseases?


Hématologie. Volume 16, Number 3, 198-207, mai-juin 2010, Revue

Résumé   Article gratuit  

Author(s) : David M Smadja, Ivan Bieche, Martine Aiach, Pascale Gaussem

Summary : Injection of endothelial progenitor cells (EPC) expanded ex vivo or isolated from bone marrow mononuclear cells improves neovascularization in both preclinical models of ischemia and in human ischemic diseases. However, the origin and identity of the cell population responsible for these clinical benefits are controversial. Given the potential usefulness of EPC as a cell therapy product, their thorough characterization is of major importance. This review describes the two cell populations currently called EPC and the issues to find differential phenotypic markers. We show that BMP2/4 are specific markers of late EPC that play a key role in EPC commitment and outgrowth during neovascularization. Several authors have attempted to expand EPC ex vivo in order to obtain an homogeneous cell therapy product. However methods developed with cord blood cells are not easily applicable to adult EPC. Thus, one of the therapeutic possibilities would be to derive endothelial cells from embryonic cells or from “iPS” (induced pluripotent stem cells). Their use as a cell therapy product for cardiovascular diseases raises some ethical concerns as well as the risk of side effects such as teratoma formation. Finally, the growing knowledge of the factors involved in pluripotency, renewal and differentiation will lead to an optimal use of adult stem cells.

Keywords : endothelial progenitor cells, thrombin, PAR-1, bone morphogenetic proteins, expansion, embryonic stem cells

 

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