title: TNFR gene-modified mesenchymal stem cells attenuate inflammation and cardiac dysfunction following MI.
abstract: OBJECTIVE
  To investigate the protective effect of tumor necrosis factor receptor (TNFR) gene modified mesenchymal stem cells (MSCs) transplantation against inflammation and cardiac dysfunction following acute myocardial infarction (AMI).
  
  
  METHODS
  MSCs were extracted from the tibias and femurs of rats and transfected with recombinant adeno-associated viral (rAAV) expressing EGFP (enhanced green fluorescent protein) or p75 (human 75 kilodalton) TNFR at multiplicity of infection of 10(5) particles/cell. Rats with AMI induced by occlusion of the left coronary artery were randomized to MSCs-TNFR transplantation group, MSCs-EGFP transplantation group and MI control group.
  
  
  RESULTS
  The effects of MSCs-TNFR transplantation on cardiac inflammation and left ventricular dysfunction were observed after 2 weeks of MI. We found that: 1) MSCs-TNFR transplantation attenuated protein production and gene expression of inflammatory cytokines TNF-, IL-1beta and IL-6; 2) MSCs-TNFR transplantation inhibited cardiomyocytes apoptosis and 3) MSCs-TNFR transplantation improved left ventricular function.
  
  
  CONCLUSIONS
  The experimental data show that transplantation with rAAV-TNFR transfected MSCs improves left ventricular function following MI through anti-apoptotic and anti-inflammatory mechanisms.
authors.affiliation: Cardiovascular Research Institute, Xianning College, and Department of Cardiology, Renmin Hospital, Hubei, PR China.
authors.forename: Cuiyu
authors.initials: C
authors.lastname: Bao
authors.forename: Jun
authors.initials: J
authors.lastname: Guo
authors.forename: Guosheng
authors.initials: G
authors.lastname: Lin
authors.forename: Mingyan
authors.initials: M
authors.lastname: Hu
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Hu
mesh_terms: D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D000229:Dependovirus / Q000235:genetics; D004195:Disease Models, Animal; D015536:Down-Regulation; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D009203:Myocardial Infarction / Q000150:complications / Q000235:genetics / Q000378:metabolism / Q000601:surgery / Q000628:therapy*; D009205:Myocarditis / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D018487:Ventricular Dysfunction, Left / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*
chemical_list: D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D047889:Receptors, Tumor Necrosis Factor, Type II; C415902:TNFRSF1B protein, human; D014409:Tumor Necrosis Factor-alpha