[Characterization of endothelial progenitor cells and putative strategies to improve their expansion].
Injection of endothelial progenitor cells (EPC) expanded ex vivo has been shown to increase neovascularization in preclinical models of ischemia and in adult patients, but the precise 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 means to find differential phenotypic markers. We have shown that BMP2/4 are specific markers of late EPC and play a key role in EPC commitment and outgrowth during neovascularization. Several authors have attempted to expand EPC ex vivo in order to obtain a homogeneous cell therapy product. One possible mean of expanding EPC ex vivo is to activate the thrombin receptor PAR-1 with the specific peptide SFLLRN. Indeed, PAR-1 activation increases angiogenic properties of EPC through activation of SDF-1, angiopoietin and IL-8 pathways. This review summarizes the characterization of EPC and different methods of ex vivo expansion.
Smadja
David M
DM
Université Paris Descartes Inserm Unité 765, Faculté de Pharmacie AP-HP, Hôpital Européen Georges Pompidou, Service d'Hématologie Biologique, 75000 Paris, France.
Gaussem
Pascale
P
D000328:Adult; D042702:Angiopoietin-2 / Q000502:physiology; D000818:Animals; D015415:Biomarkers; D055396:Bone Morphogenetic Protein 2 / Q000032:analysis; D055415:Bone Morphogenetic Protein 4 / Q000032:analysis; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects; D054377:Chemokine CXCL12 / Q000494:pharmacology / Q000502:physiology; D042783:Endothelial Cells / Q000166:cytology*; D006801:Humans; D016209:Interleukin-8 / Q000502:physiology; D007511:Ischemia / Q000601:surgery; D051379:Mice; D039902:Multipotent Stem Cells / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation; D018919:Neovascularization, Physiologic; D010446:Peptide Fragments / Q000494:pharmacology; D044463:Receptor, PAR-1 / Q000187:drug effects; D054387:Receptors, CXCR / Q000187:drug effects / Q000502:physiology; D013917:Thrombin / Q000502:physiology; D046509:Tissue Culture Techniques
D042702:Angiopoietin-2; C525718:BMP2 protein, human; C525809:BMP4 protein, human; D015415:Biomarkers; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D016209:Interleukin-8; D010446:Peptide Fragments; D044463:Receptor, PAR-1; D054387:Receptors, CXCR; C082835:thrombin receptor peptide (42-47); D013917:Thrombin