Transplantation with survivin-engineered mesenchymal stem cells results in better prognosis in a rat model of myocardial infarction
1 Department of Cardiology, Union Hospital, Fujian Provincial Institute of Coronary Disease, Fujian Medical University, Fuzhou 350001, P.R. China
2 Key Laboratory of Optoelectronic Science and Technology for Medicine, Ministry of Education, Fujian Normal University, Fuzhou 350007, P.R. China
3 Department of Neurology, Union Hospital, Fujian Medical University, Fuzhou 350001, P.R. China
4 Department of Cardiology, 1st Hospital of Xiamen, Fujian Medical University, Xiamen 362000, P.R. China
* Corresponding author. Tel: +86 591 83357896, Fax: +86 591 83308713, Email: lianglongchen{at}126.com
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Abstract |
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Aims: To investigate the effect of survivin (SVV)-engineered mesenchymal stem cells (MSCs) on post-infarction cardiac performance and remodelling in rats.
Methods and 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 µL of phosphate-buffered saline without cells (group vehicle) or containing 2 million MSCGFP (group MSCGFP) or MSCSVV (group MSCSVV) cells. Cellular survival assessed by reverse transcriptase–polymerase chain reaction for GFP in the MSCSVV group was 2.5-fold higher at 7 days and 4.3-fold higher at 28 days after transplantation than in the MSCGFP group. When compared with transplantation with MSCGFP, transplantation with MSCSVV 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.
Conclusion: Transplantation with SVV-engineered MSCs by lentiviral vector leads to better prognosis for MI by enhancing cellular survival.
Key Words: Myocardial infarction • Mesenchymal stem cells • Gene therapy • Survivin • Lentiviral vector
Received April 1, 2009; Revised August 14, 2009; Accepted August 26, 2009
The first three authors contributed equally to this paper.