Endothelial progenitor cells: characterization, in vitro expansion, and prospects for autologous cell therapy.
Injection of hematopoietic stem cells or endothelial progenitor cells (EPCs) expanded ex vivo has been shown to augment neovascularization in adult patients, but the precise origin and identity of the cell population responsible for these clinical benefits are controversial. The limited quantity of EPCs in the circulation has been the main obstacle to clinical trials. Several authors have therefore attempted to expand these cells ex vivo in order to obtain a homogeneous cell therapy product. One possible means of expanding EPCs ex vivo is to activate the thrombin receptor PAR-1 with the specific peptide SFLLRN. Indeed, PAR-1 activation promotes cell proliferation and C-X-C chemokine receptor type 4 (CXCR4) dependent migration and differentiation, with an overall angiogenic effect. This review summarizes the results and rationale of clinical trials of angiogenic therapy, the nature of EPCs, the different methods of ex vivo expansion, and current methods of quantification.
Smadja
D M
DM
INSERM Unité 765, Paris, France.
Cornet
A
A
Emmerich
J
J
Aiach
M
M
Gaussem
P
P
D043925:Angiogenesis Inducing Agents / Q000494:pharmacology; D000826:Animal Testing Alternatives; D000818:Animals; D016026:Bone Marrow Transplantation / Q000379:methods*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002986:Clinical Trials as Topic; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000502:physiology; D006801:Humans; D007511:Ischemia / Q000628:therapy; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology; D044463:Receptor, PAR-1 / Q000187:drug effects / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000187:drug effects / Q000378:metabolism; D014182:Transplantation, Autologous
D043925:Angiogenesis Inducing Agents; D010446:Peptide Fragments; D044463:Receptor, PAR-1; D019718:Receptors, CXCR4; C082835:thrombin receptor peptide (42-47)