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J Thorac Cardiovasc Surg 2006;132:1329-1338
© 2006 The American Association for Thoracic Surgery

Cardiopulmonary Support and Physiology

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

Sheng-Dong Huang, MD, PhDa, Fang-Lin Lu, MD, PhDa, Xun-Yu Xu, MD, PhDa, Xiao-Hong Liu, MD, PhDa, Xian-Xian Zhao, MD, PhDb, Bao-Zhen Zhao, MD, PhDc, Li Wang, MD, PhDd, De-Jun Gong, MD, PhDa, Yang Yuan, MD, PhDa, Zhi-Yun Xu, MD, PhDa,*

a Institute of Thoracic Cardiac Surgery, Changhai Hospital Second Military Medical University, Shanghai, People’s Republic of China
b Department of Cardiology, Changhai Hospital Second Military Medical University, Shanghai, People’s Republic of China
c Department of Ultrasound, Changhai Hospital Second Military Medical University, Shanghai, People’s Republic of China
d Department of Radiology, Changhai Hospital Second Military Medical University, Shanghai, People’s Republic of China

Received for publication May 12, 2006; revisions received July 7, 2006; * Address for reprints: Zhi-Yun Xu, MD, PhD, Institute of Thoracic Cardiac Surgery, Changhai Hospital, 174 Changhai Rd, Shanghai, 200433, People’s Republic of China (Email: zhiyunxu{at}smmu.edu.cn).

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 108 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 109 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.

Abbreviations and Acronyms AdAng group = pigs injected with adenovirus containing angiogenin; AdNull group = pigs injected with null adenovirus; DiI = 1,1'-Dioctadecyl-3,3,3',3'-tetramethylindecarboxyanino; FAC = fractional area change; LV = left ventricular; LVEF = left ventricular ejection fraction; MRI = magnetic resonance imaging; MSC = mesenchymal stem cell; MSCAdAng group = pigs implanted with angiogenin-transfected MSCs; MSCAdNull group = pigs implanted with null adenovirus-transfected MSCs; PFU = plaque forming unit






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