Abstract 1267: Intracoronary Administration of Cardiac Stem Cells Improves Cardiac Function in Pigs with Old Infarction
Previous studies have shown that intracoronary administration of cardiac stem cells (CSCs) ameliorates left ventricular (LV) remodeling in rodents with acute myocardial infarction (MI). The present study was undertaken to determine whether intracoronary CSCs are beneficial in the setting of an old MI in a large, clinically-relevant animal species. Pigs underwent a 90-min coronary artery occlusion followed by reperfusion. At the time of coronary occlusion, the right atrial appendage was harvested for isolation and expansion of c-kit+ CSCs. At an average of 96 days after MI, either autologous CSCs (n=11) or vehicle (n=10) were infused into the infarct-related artery using a balloon catheter. At this time, LV ejection fraction and systolic thickening fraction (echocardiography) and LVEDP and LV dP/dt (Millar catheter) were similar in control and CSC-treated pigs, indicating that the extent of damage inflicted by the infarction was similar in the two groups. One month later, however, CSC-treated pigs exhibited increased LV ejection fraction (51.7 ± 2.0 % vs. 42.9 ± 2.3 %, P<0.01) and greater systolic thickening fraction in the infarcted LV wall relative to control pigs (31.7 ± 2.4 % vs. 21.1 ± 2.4 % in controls, P<0.01), as well as lower LVEDP (11.8 ± 1.0 mmHg vs. 15.1 ± 1.3 mmHg in controls, P<0.01) and increased max LV dP/dt (1,251 ± 74 mmHg/s vs. 976 ± 88, P<0.02). Confocal microscopy showed that clusters of small alpha-sarcomeric actin positive cells expressing Ki67 (a marker of cell division) were present in the scar of treated pigs, consistent with cardiac regeneration. The origin of these cycling myocytes from the injected cells was confirmed in four pigs that received EGFP-labeled CSCs. In conclusion, intracoronary infusion of autologous CSCs improves regional and global LV function and promotes cardiac regeneration in pigs with chronic MI. These findings lay the groundwork for clinical trials of CSCs in patients undergoing CABG surgery.