Transplanted Skeletal Myoblasts Can Fully Replace the Infarcted Myocardium When They Survive in the Host in Large Numbers

Abstract

BACKGROUND: It is not clear how many skeletal myoblasts (SM) can survive and exert beneficial effects in the host myocardial infarction (MI) area. We assessed the hypothesis that a large number of SM can replace the MI area with reverse left ventricular (LV) remodeling. METHODS AND RESULTS: MI was created by left coronary artery ligation in male Lewis rats. Four weeks after ligation, 45 rats had skeletal myoblast transplantation in the MI area. They were randomized into 3 groups according to the number of SM: group I (n=15), 5 x 10(7); group II (n=15), 5 x 10(6); and group III (n=15), 5 x 10(5) cells. Donor SM were obtained from neonatal Lewis rats and directly used without expansion. Another four weeks later, all rats were sacrificed following hemodynamic assessment. All heart sections were stained with anti-fast skeletal myosin heavy chain (FSMHC) antibody to determine the spacial extent of donor myocytes. RESULTS: Four weeks after transplantation, LV diastolic dimension was decreased, fractional area change was increased, and MI size was decreased maximally in group I. Histological study showed that donor cells positive for FSMHC occupied the MI area with nearly normal wall thickness in group I, in which estimated volume of donor-derived muscle tissue was 40 mm3. In the other groups, FSMHC-positive cells were found only partly in the MI area. CONCLUSIONS: A large number of freshly isolated neonatal SM can survive in the host and fully replace the infarcted myocardium with reverse LV remodeling in rats with MI.