MATERIALS AND METHODS: The MSCs were separated and genetically engineered using ex-vivo myr-Akt-adenoviral gene transfer. The MSCs were delivered by intracoronary injection into infarcted porcine myocardium [group I (control: n=8), media only; group II (n=8), MSCs only; group III (n=8), MSCs modified with Akt]. Myocardial SPECT was performed before and 4 weeks after the MSC transplantation, with the pigs sacrificed for immunocytochemical staining and histological analyses for apoptosis and fibrosis.

RESULTS: The left ventricular ejection fractions (LVEF) were 44.7±16.6, 35.9±10.0 and 41.1±7.9% at first (each n=8), which changed to 29.7±8.5, 39.0±9.5 and 60.4±16.6% at 4 weeks after the MSC implantation in groups I, II and III, respectively. The myocardial infarction (MI) area changed from 17.6±9.2, 35.0±11.8 and 24.3±11.2% to 19.6±10.1, 27.2±13.9 and 7.4±5.3% in groups I, II and III, respectively. Transplantation of 1X10(7) cells into group II increased the deltaLVEF (-15.0±15.3 vs. 3.0±4.3%, n=8 in each, p=0.016) and decreased the deltaMI area (2.1±0.9 vs. 5.6±3.1%, n=8 in each, p=0.04) compared to those of the control group, and these changes were more significant in the deltaLVEF (19.3±15.7%, p=0.006) and deltaMI area (-16.4±6.1%, p=0.037) of group III.

CONCLUSION: MSCs transduced with Akt enhance the repair of the injured area, prevent remodeling and restore systolic performance in infarcted porcine myocardium.