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 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.
Conclusion: Transplantation with SVV-engineered MSCs by lentiviral vector leads to better prognosis for MI by enhancing cellular survival.