The effects of mesenchymal stem cells transduced with Akt in a porcine myocardial infarction model

Objective: This study was designed to examine whether mesenchymal stem cells (MSCs) transduced with Akt enhance cardiac repair after transplantation into the ischemic porcine heart. Methods: MSCs isolated from porcine bone marrow and transduced with myr-Akt were transplanted into porcine hearts after experimental myocardial infarction (MI) using intracoronary injection [Group I, vehicle; Group II, MSCs; Group III, Akt-MSCs]. Myocardial single photon emission tomography (M-SPECT) was performed to assess myocardial function and the infarcted area. Pigs were also sacrificed for immunohistochemical characterization and histologic analysis. In addition, in vitro assays were performed to examine the resistance of Akt-MSCs to H₂O₂ stimulation. Results: Transplantation of MSCs into the ischemic porcine myocardium (Group II) increased the left ventricular ejection fraction (ΔLV EF; - 6.3 ± 15.1% versus 0.5 ± 6.4%, P < 0.001) and decreased the Δarea of MI (6.8 ± 5.6% versus - 5.0 ± 5.3%, P < 0.001) compared with the vehicle control (Group I). Transplantation of MSCs transduced with myr-Akt (Group III) resulted in further improvement in ΔLV EF (- 6.3 ± 15.1% versus 5.8 ± 11.3%, P < 0.001) and in Δarea of MI (6.8 ± 5.6% versus - 17.0 ± 7.6%, P < 0.001). Akt-MSCs were more resistant to apoptosis, and the levels of extracellular signal-regulated protein kinase (ERK) activation and vascular endothelial growth factor (VEGF) were higher in H₂O₂-stimulated Akt-MSCs. Conclusion: Cellular transplantation of Akt-MSCs further enhances the repair of injured myocardium compared to MSC transplantation alone by increasing the number of viable MSCs after cellular transplantation.