Insulin-like growth factor-1 enhances the efficacy of myoblast transplantation with its multiple functions in the chronic myocardial infarction rat model

Background: Myoblast transplantation (Tx) is promising for the improvement of cardiac function in ischemic cardiomyopathy. Insulin-like growth factor-1 (IGF-1) has anti-apoptotic and angiogenic effects, and induces myocyte hypertrophy. Our hypothesis is that topical and slow-release IGF-1 enhances the efficacy of Tx through its multiple functions. Methods: Four weeks after coronary artery ligation, Lewis rats were divided into four groups: (1) IGF-1+Tx, injection of 6 x 10(6) myoblasts into the infarcted area with placement of an IGF-1-impregnated sheet on the left ventricular (LV) free wall; (2) Tx, Tx alone; (3) IGF-1, IGF-1 sheet alone; and (4) control. We measured cardiac function and performed immunohistochemical examinations. Results: At 4 weeks after treatment, LV diastolic dimension was the smallest, end-systolic elastance was the highest, and T was the smallest in the IGF-1+Tx group. The graft volume in the IGF-1+Tx group was 3-fold larger than in the Tx group. One day after transplantation, TUNEL-positive donor cells were fewer in the IGF-1+Tx than in the Tx group. Western blot analysis demonstrated that the phosphorylation of Akt increased and the expression of Bax decreased in the transplanted area of IGF-1+Tx rats compared with Tx rats. The vascular density in the peri-infarcted area was larger in IGF-1+Tx than in Tx rats. The mean diameter of graft-derived myotubes was larger in IGF-1+Tx than in Tx animals. Conclusions: IGF-1 increases the graft volume and enhances the efficacy of Tx in the chronic myocardial infarction model due to its multiple effects of preventing apoptosis, inducing angiogenesis, and promoting rnyoblast growth.