89 Review www.expert-reviews.com ISSN 1473-7159 © 2010 Expert Reviews Ltd 10.1586/ERM.09.80 The endothelial monolayer represent a dynamic physiological border between circulating blood and the surrounding tissue, but also produces a variety of important vasoregulatory factors that bestow on it antithrombotic proper- ties [1] . Acute or chronic injuries lead to the loss of this protective role and to the acquisi- tion of vasoconstraining and prothrombotic properties. This pathological vessel remodel- ing gradually results in the development of atherosclerotic plaques [2] . It is noteworthy that the endothelium has the ability to repair itself [3] : endothelial cells (ECs) at the edges of the lesion proliferate and migrate toward the center owing to lost contact inhibition. If the endothelium is young and healthy, the local repair process is complete and the intimal layer is reconstituted; on the contrary, if the endo- thelium receives the assaults of more than one risk factor (e.g., hypertension, smoking, hyper- cholesterolemia or hyperglycemia), local repair is defective and a plaque may develop as result of an infammatory process elicited mainly by macrophage accumulation [4] . Furthermore, mature ECs are terminally differentiated, with a low proliferative potential, and their capac- ity to substitute damaged endothelium is lim- ited. Therefore, the endothelial repair needs the support of other cells types that have the potential to differentiate into mature ECs and have, therefore, been termed endothelial pro- genitor cells (EPCs) [2] . Although some EPCs in circulating blood are of non-bone marrow (BM) origin (from fat tissue, spleen, liver, intestine and vessel wall) [5] , the majority of these cells originate from the hematopoietic stem cells of the BM. Under steady-state con- ditions, these cells are maintained inactive and contact the BM stroma; specifc signals stimulate the stem cells to differentiate and to shift from the quiescent stromal niche into the systemic circulation [6,7] , contributing to the neoangiogenic process and repair of the damaged endothelial monolayer. EPC defnition & characterization Despite many published data, the exact origin and functional de fnition of EPCs remains rather controversial. This is related to many factors, some of which are related to the varia- tion in the research protocols utilized but oth- ers are out of the control of the investigator, such as the wide heterogeneity of the vascular bed throughout the body, which may deter- mine a different response of the endothelium to injuries, also involving EPC recruitment from the peripheral blood [8] . Therefore, many authors agree that the main feature of EPCs is the ability to directly participate in vessel growth by differentiation into ECs in vivo. Carlo Foresta † , Luca De Toni, Alberto Ferlin and Antonella Di Mambro † Author for correspondence University of Padova, Department of Histology, Microbiology and Medical Biotechnologies, Centre for Male Gamete Cryopreservation, Via Gabelli 63, 35121 Padova, Italy Tel.: +39 049 821 8517 Fax: +39 049 821 3222 carlo.foresta@unipd.it The exact origin and functional defnition of endothelial progenitor cells (EPCs) remains rather controversial, but many authors agree that the main feature of EPCs is the ability to directly participate in vessel growth by differentiation into endothelial cells in vivo. The majority of these cells originate from the hematopoietic stem cells of the bone marrow and, under specifc signals, differentiate and shift into the systemic circulation, contributing to the neoangiogenic process and repair of the damaged endothelial monolayer. Recently, it has been demonstrated that the number and function of EPCs is positively linked with an improved endothelial function or regeneration but inversely correlated with cardiovascular risk factors: a reduced number of EPCs is an independent predictor of morbidity and mortality of cardiovascular diseases and of atherosclerotic disease progression. Owing to their role in endogenous maintenance and repair of damaged endothelium, EPCs have been examined for therapeutic potential in ischemic diseases and there are evidence-based perspectives regarding their use for vascular regenerative medicine. KEYWORDS: cardiovascular risk factor • endothelial function • endothelial progenitor cell • neovascularization Clinical implication of endothelial progenitor cells Expert Rev. Mol. Diagn. 10(1), 89–105 (2010) For reprint orders, please contact reprints@expert-reviews.com