Transplantation with survivin-engineered mesenchymal stem cells results in better prognosis in a rat model of myocardial infarction

To investigate the effect of survivin (SVV)-engineered mesenchymal stem cells (MSCs) on post-infarction cardiac performance and remodelling in rats. 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 mu L 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. Transplantation with SVV-engineered MSCs by lentiviral vector leads to better prognosis for MI by enhancing cellular survival.