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

Abstract

AimsTo investigate the effect of survivin (SVV)-engineered mesenchymal stem cells (MSCs) on post-infarction cardiac performance and remodelling in rats. Methods and resultsMesenchymal 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 ¼ 18 per group) to receive intra-myocardial injections of 100 mL of phosphatebuffered 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. ConclusionTransplantation with SVV-engineered MSCs by lentiviral vector leads to better prognosis for MI by enhancing cellular survival.--

Umbilical cord mesenchymal stem cell transplantation in severe and refractory systemic lupus erythematosus

“…Recent studies have indicated that these pluripotent cells also differentiate into endoderm and neuroectoderm lineages, including neurons, hepatocytes, and cardiocytes (8)(9)(10)). An important function of MSCs for autoimmune diseases is their immunomodulatory effect on various activated lymphoid cells, such as T cells, B cells, natural killer cells, and dendritic cells (11)(12)(13).…”

Mutation detection in the promoter region of survivin gene on N-methyl-N-nitrosourea induced colon tumor model in experiment

“…In a similar study Lin Fan et al showed that overexpression of survivin promoted mesenchymal stem cell (MSCs) survival in the infarcted myocardium and also enhanced the secretion effect of MSCs for vascular endothelium growth factor in vitro and in vivo in a rat model. This led to angiogenesis in the infarcted myocardium and ultimately reduced the infarct size, inhibited myocardial remodeling, and resulted in substantial recovery of cardiac function after myocardial infarction (16). In another study, Chen et al investigated the protein and mRNA expression of survivin, as well as the methylation status of the CpG sites in exon 1 of the survivin gene for 7,12 dimethylbenz[a]anthracene (DMBA)-induced hamster buccal-pouch squamous-cell carcinomas.…”

Myocardial Regeneration for Humans ― Modifying Biology and Manipulating Evolution ―

“…Primates date back 75 M years, while the genus Homo is 2.5 M years old and our within stem cells intended to increase repair and the regenerative response after adoptive transfer. Improvement of cellular survival and/or proliferation after injection into the damaged myocardium has been effected with MSCs engineered to overexpress Bcl-2, 33 AKT 34 or survivin, 35 whereas CPCs have been engineered with AKT, 36 as well as with Pim-1, a pro-survival serine/threonine kinase downstream of AKT. 37-39 Vascularization of the infarcted and border zone regions of damaged myocardium was increased using MSCs enhanced with VEGF and Ang1, 40 and CPCs have been enhanced with Notch, 41 and EPCs have been enhanced with endothelial nitric oxide synthase and heme oxygenase-1.…”