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 MSC(AdAng) or MSC(AdNull) 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 MSC(AdAng) 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 MSC(AdNull) 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 MSC(AdAng) 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.
Huang
Sheng-Dong
SD
Institute of Thoracic Cardiac Surgery, Changhai Hospital Second Military Medical University, Shanghai, People's Republic of China.
Lu
Fang-Lin
FL
Xu
Xun-Yu
XY
Liu
Xiao-Hong
XH
Zhao
Xian-Xian
XX
Zhao
Bao-Zhen
BZ
Wang
Li
L
Gong
De-Jun
DJ
Yuan
Yang
Y
Xu
Zhi-Yun
ZY
D000818:Animals; D002478:Cells, Cultured; D002908:Chronic Disease; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000503:physiopathology*; D012259:Ribonuclease, Pancreatic / Q000096:biosynthesis* / Q000235:genetics; D033581:Stem Cell Transplantation; D013552:Swine
C046366:angiogenin; D012259:Ribonuclease, Pancreatic