The Effects of Mesenchymal Stem Cells Transduced with Akt in a Porcine Myocardial Infarction Model

ABSTRACT

BACKGROUND AND OBJECTIVES: This study was designed to examine whether mesenchymal stem cells (MSCs) transduced with Akt are more resistant to apoptosis, and enhance cardiac repair, following the transplantation into infarcted porcine myocardium. 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.