Background: Mesenchymal stem cells (MSCs) derived from bone marrow are self-renewing, clonal precursors of non-hematopoietic tissues and can differentiate into cardiac muscle in vitro and in vivo. But, it has been observed that transplantation of MSCs into infarcted porcine hearts yield only marginal improvement in cardiac function. This study was designed to elucidate the Akt (a serine threonine kinase and powerful survival signal in many systems)-engineered bone marrow derived MSCs are more resistant to apoptosis and MSCs can enhance cardiac repair after transplantation into the ischemic porcine heart. Methods and Materials:We separated MSCs from hematopoietic cells based on their preferential attachment to polystyrene surfaces. We genetically engineered MSCs using ex-vivo myr Akt-adenoviral trasnduction. The MSCs were delivered by intracoronary injection to porcine myocardial infarction (MI) model [group I (control; n=5), media only; group II (n=5), MSCs only; group III (n=5), MSCs modified with Akt]. Myocardial SPECT was performed before and 4 weeks after the MSC implantation and pigs were sacrified for immunocytochemical characterization using CD34 (ICO115), integrin 慣���, Vimentin, and 慣-sarcomeric actin. Results: Mean LV ejection fraction (EF) was 44.8짹16.6% in group I vs. 30.0짹7.6% in group II at first (each n=5), and changed to 29.8짹8.5% vs. 39.0짹9.5% at 4 weeks after the MSC implantation. Mean MI area was 17.5짹9.2% vs. 35.0짹11.9% at first, and changed to 19.6짹10.1% vs. 27.2짹13.9%, in group I and II respectively. Transplantation of ~10⁷ cells into the ischemic porcine myocardium in group II increased the ���LV EF (-14.9짹15.3% vs. 9.0짹8.6%, n=5 in each, p=0.016) and decreased the ���area of MI (-2.1짹1.3% vs. 7.9짹9.0%, n=5 in each, p=0.04) compared with control group. Conclusion: MSCs may repair infarcted area, prevent remodeling, and restore systolic performance of infarcted hearts. Final histopathologic findings and the results of MSCs modified with Akt will be presented in October.