Endothelial and cardiac progenitor cells for cardiovascular repair: A controversial paradigm in cell therapy

Stem cells have the potential to differentiate into cardiovascular cell lineages and to stimulate tissue regeneration in a paracrine/autocrine manner; thus, they have been extensively studied as candidate cell sources for cardiovascular regeneration. Several preclinical and clinical studies addressing the therapeutic potential of endothelial progenitor cells (EPCs) and cardiac progenitor cells (CPCs) in cardiovascular diseases have been performed. For instance, autologous EPC transplantation and EPC mobilization through pharmacological agents contributed to vascular repair and neovascularization in different animal models of limb ischemia and myocardial infarction. Also, CPC administration and in situ stimulation of resident CPCs have been shown to improve myocardial survival and function in experimental models of ischemic heart disease. However, clinical studies using EPC- and CPC-based therapeutic approaches have produced mixed results. In this regard, intracoronary, intra-myocardial or intramuscular injection of either bone marrow-derived or peripheral blood progenitor cells has improved pathological features of tissue ischemia in humans, despite modest or no clinical benefit has been observed in most cases. Also, the intriguing scientific background surrounding the potential clinical applications of EPC capture stenting is still waiting for a confirmatory proof. Moreover, clinical findings on the efficacy of CPC-based cell therapy in heart diseases are still very preliminary and based on small-size studies. Despite promising evidence, widespread clinical application of both EPCs and CPCs remains delayed due to several unresolved issues. The present review provides a summary of the different applications of EPCs and CPCs for cardiovascular cell therapy and underlies their advantages and limitations.