Erythropoietin improves the efficiency of endothelial progenitor cell therapy after myocardial infarction in mice: Effects on transplanted cell survival and autologous endothelial progenitor cell mobilization

Background: Endothelial progenitor cells (EPCs) participate in vascular repair and angiogenesis. Thus, EPC transplantation into ischemic myocardium might improve cardiac function; however, the vast majority of cells die within a short period. The present study was designed to investigate whether exogenous erythropoietin (EPO) delivery could improve the survival of transplanted EPCs and enhance the efficiency of EPC-based cell therapy. Methods: Myocardial infarction was induced in wild-type mice by ligating the left anterior descending coronary artery. Enhanced green fluorescent protein-EPCs with or without EPO were transplanted into peri-infarct myocardium. Enhanced green fluorescent protein-EPCs were detected 7 and 28 d after surgery. The amount of circulating EPCs was analyzed 3 and 28 d after surgery. The stromal cell-derived factor-1 alpha and vascular endothelial growth factor concentrations, microvessel density, apoptosis, fibrosis in the peri-infarct myocardium, and cardiac function were compared among the groups. Results: More enhanced green fluorescent protein-EPCs were found in the hearts treated with EPC + EPO than in those treated with EPC alone. The circulating EPC level was markedly elevated after EPC + EPO treatment compared with EPC application alone. Stromal cell-derived factor-1 alpha and vascular endothelial growth factor were increased accordingly, along with increased microvessel density, decreased apoptosis, and reduced fibrosis in the peri-infarct myocardium. Left ventricular fractional shortening was greater and the interventricular septum was thicker after EPC + EPO treatment compared with EPC treatment alone. Conclusions: EPO improved the efficiency of EPC therapy in mice with myocardial infarction. This effect was associated with enhanced transplanted EPC survival and autologous EPC mobilization. (C) 2012 Elsevier Inc. All rights reserved.