Abstract 207: Intracoronary Administration of Cardiac Stem Cells Repairs Infarcted Myocardium and Improves Cardiac Function in Rats with Old Infarction
We have previously shown that in rats with acute myocardial infarction (MI), intracoronary administration of cardiac stem cells (CSCs) at 4 hours after reperfusion is effective in regenerating cardiac myocytes and ameliorating LV function. The clinical applicability of this paradigm, however, is limited by the fact that in patients with acute MI expansion of autologous CSCs from endomyocardial biopsies requires several weeks, by which time the infarct is a scar and inflammation has resolved. We therefore determined whether CSCs are beneficial in the more clinically relevant setting of an old MI (scar). Rats underwent a 2-hour coronary occlusion followed by reperfusion; 1 month later, they received vehicle (control, n = 14) or EGFP-labeled CSCs (n =16) into the aortic root during aortic occlusion. At 35 days after CSC injection, CSC-treated rats exhibited improved LV ejection fraction (echocardiography) and hemodynam-ics (LVEDP, dP/dtmax, end-systolic elastance [Ees] [conductance catheter]) (Figure⇓). The percentage of viable myocardium in the risk region was significantly higher and the thickness of the infarcted wall tended to be greater in CSC-treated rats (morphometry) (Figure⇓). EGFP-positive myocytes (expressing α-sarcomeric actin) were observed in the infarct and border zone of CSC-treated rats (microscopy). We conclude that intracoronary delivery of CSCs promotes regeneration of myocytes and improves LV function even as late as 1 month after MI, when the infarcted tissue has already been replaced by a scar. These results open new therapeutic applications for the use of autologous CSCs in the large population of patients with old MI and chronic ischemic cardiomyopathy.