Transplantation of angiogenin-overexpressing mesenchymal stem cells synergistically augments cardiac function in a porcine model of chronic ischemia

Objective: Accumulated evidence suggests that myogenesis and angiogenesis induced by implanted cells play important roles in restoring cardiac function after a myocardial infarction. The current study investigated the effects of transplanted autologous mesenchymal stem cells overexpressing angiogenin on myocardial perfusion and cardiac function in the porcine chronic ischemic model. Methods: Chronic ischemia was generated in Yorkshire pigs by placing an ameroid constrictor around the left circumflex artery. Four weeks after occlusion, the animals were randomly separated into 4 groups: pigs in the MSCAdAng or MSCAdNull groups were implanted with 6 X 10(8) mesenchymal stem cells infected with adenovirus containing angiogenin gene or null adenovirus, respectively; pigs in the AdAng or AdNull groups were injected intramyocardially with adenovirus (5 X 10(9) plaque forming unit/pig) containing angiogenin gene or null adenovirus, respectively. Four weeks after implantation, mesenchymal stem cells prelabeled with DiI were observed within the implanted area in both cell transplantation groups. Results: Angiogenin protein levels were significantly greater in the MSCAdAng and AdAng groups than in the other 2 groups and were associated with greater neovessel formation than in the other 2 groups. Mesenchymal stem cell transplantation decreased scar size and increased scar thickness. Both the AdAng and MSCAdNull groups experienced improved cardiac function compared with that seen in the AdNull group. However, a synergistic effect of mesenchymal stem cells and angiogenin was observed in the MSCAdAng group because myocardial perfusion and cardiac function increased significantly (P < .05 for all groups) in this group compared with all the others. Conclusions: Transplantation of autologous mesenchymal stem cells transfected with the angiogenin gene revealed a synergistic effect on the improvement of heart perfusion and function after ameroid occlusion.