title: Enhancement of the survival of engrafted mesenchymal stem cells in the ischemic heart by TNFR gene transfection.
abstract: Autologous or allogeneic mesenchymal stem cells (MSCs) have been used as one of the potential cell sources for cellular cardiomyoplasty. The adverse microenvironment in acute myocardial infarction, however, is considered a deleterious factor for MSC transplantation and cell survival. Tumor necrosis factor (TNF)-alpha is an inflammatory mediator produced during ischemia that may affect the survival of MSCs. In this study, we investigated the enhancement of MSC survival by transfecting cells with the TNF receptor (TNFR) gene, leading to the overproduction of TNFR and the binding of TNF-alpha. Rats with acute myocardial infarction, induced by the occlusion of the left coronary artery, were transplanted with MSC or MSC-TNFR. After 2 weeks of acute myocardial infarction, cardiac function was assessed. Engrafted MSC survival and localization of TNF-alpha protein in infarction myocardium were evaluated. The levels of TNF-alpha and TNFR in the infarction zone were assessed. The results indicate that MSC-TNFR transplantation (1) improved left ventricular function; (2) enhanced engrafted MSC survival in the infarcted myocardium; (3) attenuated the level of TNF-alpha in serum and cardiac tissue; and (4) increased TNFR protein production in the infarcted myocardium. Our results showed that MSC modified by the TNFR gene improved cell viability and thereby has the potential to improve the efficiency of MSC transplantation therapy in the ischemic heart.
authors.affiliation: Cardiovascular Research Institute, Xianning College, Xianning, P.R. China. bcy_tiaopi@126.com
authors.forename: Cuiyu
authors.initials: C
authors.lastname: Bao
authors.forename: Jun
authors.initials: J
authors.lastname: Guo
authors.forename: Min
authors.initials: M
authors.lastname: Zheng
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.forename: Guosheng
authors.initials: G
authors.lastname: Lin
authors.forename: MingYan
authors.initials: M
authors.lastname: Hu
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000235:genetics; D006085:Graft Survival / Q000235:genetics / Q000502:physiology; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D017202:Myocardial Ischemia / Q000097:blood / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy*; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics* / Q000502:physiology; D014162:Transfection / Q000379:methods; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D015854:Up-Regulation / Q000235:genetics; D018487:Ventricular Dysfunction, Left / Q000097:blood / Q000235:genetics / Q000503:physiopathology
chemical_list: D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha