Transplantation with survivin-engineered mesenchymal stem cells results in better prognosis in a rat model of myocardial infarction.
OBJECTIVE
To investigate the effect of survivin (SVV)-engineered mesenchymal stem cells (MSCs) on post-infarction cardiac performance and remodelling in rats.


RESULTS
Mesenchymal stem cells from male Sprague-Dawley rat bone marrow were infected with the self-inactive lentiviral vector GFP-wre-CMV/LTR and Flap-Ubiqutin promoter (GCFU) carrying green fluorescent protein (GFP) gene and SVV recombinant vector (GCFU-SVV). In vitro, modification with SVV increased the secretion of vascular endothelial growth factor (VEGF) by 1.28-fold under hypoxic conditions. In vivo, after permanent left anterior descending artery occlusion, rats were randomized (n = 18 per group) to receive intra-myocardial injections of 100 microL of phosphate-buffered saline without cells (group vehicle) or containing 2 million MSC(GFP) (group MSC(GFP)) or MSC(SVV) (group MSC(SVV)) cells. Cellular survival assessed by reverse transcriptase-polymerase chain reaction for GFP in the MSC(SVV) group was 2.5-fold higher at 7 days and 4.3-fold higher at 28 days after transplantation than in the MSC(GFP) group. When compared with transplantation with MSC(GFP), transplantation with MSC(SVV) further upregulated VEGF expression at 7 and 28 days after myocardial infarction (MI), increased capillary density by 38%, reduced the infarct size by 12.7%, significantly inhibited collagen deposition, and further improved cardiac function at 28 days after MI.


CONCLUSIONS
Transplantation with SVV-engineered MSCs by lentiviral vector leads to better prognosis for MI by enhancing cellular survival.
Fan
Lin
L
Department of Cardiology, Union Hospital, Fujian Provincial Institute of Coronary Disease, Fujian Medical University, Fuzhou 350001, People's Republic of China.
Lin
Chaogui
C
Zhuo
Shuangmu
S
Chen
Lianglong
L
Liu
Nan
N
Luo
Yukun
Y
Fang
Jun
J
Huang
Zhengrong
Z
Lin
Yunling
Y
Chen
Jianxin
J
D000818:Animals; D002470:Cell Survival; D003094:Collagen / Q000378:metabolism; D005822:Genetic Vectors / Q000235:genetics; D006085:Graft Survival; D049452:Green Fluorescent Proteins / Q000378:metabolism; D016086:Lentivirus / Q000235:genetics; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D032383:Myocytes, Cardiac / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077022:Survivin; D014161:Transduction, Genetic / Q000379:methods; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
C516989:Birc5 protein, rat; D008869:Microtubule-Associated Proteins; D000077022:Survivin; D042461:Vascular Endothelial Growth Factor A; D049452:Green Fluorescent Proteins; D003094:Collagen