Department of Cardiology, Union Hospital, Fujian Provincial Institute of Coronary Disease, Fujian Medical University, Fuzhou 350001, People's Republic of China.
Eur J Heart Fail. 2009 Nov;11(11):1023-30. doi: 10.1093/eurjhf/hfp135.
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 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.
Transplantation with SVV-engineered MSCs by lentiviral vector leads to better prognosis for MI by enhancing cellular survival.
研究 Survivin（SVV）工程化间充质干细胞（MSCs）对大鼠梗死心脏后心功能和重塑的影响。
雄性 Sprague-Dawley 大鼠骨髓间充质干细胞用携带绿色荧光蛋白（GFP）基因和 SVV 重组载体（GCFU-SVV）的自我失活慢病毒载体 GFP-wre-CMV/LTR 和 Flap-Ubiqutin 启动子（GCFU）感染。体外，SVV 修饰使缺氧条件下血管内皮生长因子（VEGF）的分泌增加 1.28 倍。在体内，永久性左前降支闭塞后，大鼠随机（每组 18 只）接受 100 μL 无细胞磷酸盐缓冲液（对照组）或含 200 万个 MSC（GFP）（MSC（GFP）组）或 MSC（SVV）（MSC（SVV）组）细胞的心肌内注射。逆转录聚合酶链反应检测 GFP 发现，MSC（SVV）组细胞在移植后 7 天和 28 天的存活率分别比 MSC（GFP）组高 2.5 倍和 4.3 倍。与 MSC（GFP）移植相比，MSC（SVV）移植进一步上调了心肌梗死后 7 天和 28 天的 VEGF 表达，增加了 38%的毛细血管密度，使梗死面积减少了 12.7%，显著抑制了胶原沉积，并进一步改善了心肌梗死后 28 天的心脏功能。
通过慢病毒载体转染 SVV 工程化 MSCs 可提高细胞存活率，改善心肌梗死后的预后。
