Therapeutic potential of ex vivo expanded endothelial progenitor cells formyocardial ischemia

Background-We investigated the therapeutic potential of ex vivo expanded en dothelial progenitor cells (EPCs) for myocardial neovascularization. Methods and Results-Peripheral blood mononuclear cells obtained from health y human adults were cultured in EPC medium and harvested 7 days later. Myoc ardial ischemia was induced by ligating the left anterior descending corona ry artery in male Hsd:RH-mu (athymic nude) rats. A total of 10(6) EPCs labe led with 1,1'-dioctadecyl-1 to 3,3,3',3'-tetramethylindocarbocyanine perchl orate were injected intravenously 3 hours after the induction of myocardial ischemia. Seven days later, fluorescence-conjugated Bandeiraea simplicifol ia lectin I was administered intravenously, and the rats were immediately k illed. Fluorescence microscopy revealed that transplanted EPCs accumulated in the ischemic area and incorporated into foci of myocardial neovasculariz ation. To determine the impact on left ventricular function, 5 rats (EPC gr oup) were injected intravenously with 10(6) EPCs 3 hours after ischemia; 5 other rats (control group) received culture media. Echocardiography, perfor med just before and 28 days after ischemia, disclosed ventricular dimension s that were significantly smaller and fractional shortening that was signif icantly greater in the EPC group than in the control group by day 28. Regio nal wall motion was better preserved in the EPC group. After euthanization on day 28, necropsy examination disclosed that capillary density was signif icantly greater in the EPC group than in the control group. Moreover, the e xtent of left ventricular scarring was significantly less in rats receiving EPCs than in controls. Immunohistochemistry revealed capillaries that were positive for human-specific endothelial cells. Conclusions-Ex vivo expanded EPCs incorporate into foci of myocardial neova scularization and have a favorable impact on the preservation of left ventr icular function.