Abstract 1449: Neovascularization and Left Ventricular Function after Myocardial Infarction in Rats are Improved by Transplantation of Endothelial Progenitor Cells
As a novel therapy for heart failure and ischemic heart disease cell transplantation has emerged as a promising future treatment. Recent reports suggest that local or systemic administration of endothelial progenitor cells (EPC) enhances ischemic neovascularization and improves function of ischemic tissues in animals with hindlimb- or myocardial ischemia. This study investigated the effect of intramyocardial transfer of human EPCs and SDF-1 (an EPC attractant chemokine) on left-ventriclur function after an acute myocardial infarction in a rat model. Human BrdU labelled EPCs (1 x 106, n=10), SDF-1 (10 μg, n=6) and medium (n=10) were injected directly into border zones of infarcted myocardium of rats, that had undergone ligation of left anterior descending artery 4 weeks before. Eight weeks after transplantation isolated heart studies according to Langendorff and echocardiography revealed a significant improvement of left ventricular function after injection of EPCs (LVDP: 83,2 ± 10,7 mmHg; FS pre TX: 27,66 ± 6,57%, FS post TX: 40,8 ± 10,9%) in contrast to injection of medium (LVDP: 68,7 ± 11,2 mmHg; FS pre TX: 31,9 ± 9,75%, FS post TX: 29,5 ± 5,42%, p<0,05). No significant functional improvement was observed in SDF-1 injected hearts. BrdU positive signals could be detected in infarcted areas with partial integration into host myocardium. The density of CD 31 positive vessels (356,25 ± 69,35 cells/mm2) and coronary flow (11,3 ± 1,6 ml/min) were significantly increased after transplantation of EPCs in contrast to medium injected hearts (CD31 pos. vessels: 246,1 ± 41,1 cells/mm2, p<0,05; coronary flow: 8,7 ± 2,4 ml/min, p<0,05). Furthermore, apoptotic cells in infarcted areas were more abundant after medium injection (263,95 ± 19,06 cells/mm2) compared to EPC-injected hearts (171,23 ± 15,14 cells/mm2) with no significant differences detected after SDF injection. In conclusion, transplantation of EPC leads to functional improvement after myocardial infarction, while SDF-1 injection alone did not affect cardiac function. Augmented coronary flow, higher density of CD 31 positive vessels and lower number of apoptotic cells suggest that the underlying mechanism of improved left ventricular function is based on enhanced neovascularization.