Endothelial progenitor cells and cardiovascular cell-based therapies

Since their initial discovery more than a decade ago, bone marrow (BM)-derived circulating endothelial progenitor cells (EPC) have been reported to play a role in postnatal vasculogenesis through vessel regeneration and remodeling. These cells have been reported to mobilize into the blood stream in response to vascular injury, and differentiate into cells expressing a host of endothelial cell (EC) markers in vitro. Because of demonstrable regenerative capacity in animal models of human disease, EPC are thought to represent a novel treatment option for problematic cardiovascular conditions such as myocardial infarction (MI) and peripheral vascular disease (PVD). Various studies have been performed to test the clinical efficacy of EPC in patients with cardiovascular disease (CVD), including the mobilization of EPC with pharmacologic agents in patients with heart disease, and harvesting of cells from the circulation and BM for autologous reinfusion in affected patients. The outcomes of these trials have been mixed and not as robust as predicted from the animal models, partly because of the variation in the definition of human EPC and the resulting heterogeneity in cell populations used in the treatments. This review will decipher a number of published studies that have been conducted to examine cell therapies for treatment of CVD, will attempt to explain why efficacy of treatment with putative EPC has been inconsistent, and predict which aspects of these trials may need to be redesigned for future successful treatment of CVD.