title: Tissue kallikrein-modified mesenchymal stem cells provide enhanced protection against ischemic cardiac injury after myocardial infarction.
abstract: BACKGROUND
  Genetically modified mesenchymal stem cells (MSCs) are a promising approach to the treatment of cardiac injury after myocardial infarction (MI).
  
  
  RESULTS
  Rat MSCs were transduced with adenovirus containing human tissue kallikrein (TK) gene (TK-MSCs), and they secreted human TK into culture medium. Cultured TK-MSCs were more resistant to hypoxia-induced apoptosis and exhibited reduced caspase-3 activity compared to control GFP-MSCs. The effect of TK-MSC injection on cardiac injury was evaluated in rats at 1 and 14 days after MI. At 1 day after MI, human TK expression in the myocardium was associated with improved cardiac function and decreased inflammatory cell accumulation, proinflammatory gene expression and apoptosis. The beneficial effect of TK-MSCs against apoptosis was verified in cultured cardiomyocytes, as TK-MSC-conditioned medium suppressed hypoxia-induced apoptosis and caspase-3 activity, and increased Akt phosphorylation. At 2 weeks after MI, TK-MSCs improved cardiac function, decreased infarct size, attenuated cardiac remodeling, and promoted neovascularization, as compared to GFP-MSCs. Furthermore, the TK-MSC-conditioned medium, containing elevated vascular endothelial growth factor levels, stimulated the proliferation, migration and tube formation of cultured human endothelial cells.
  
  
  CONCLUSIONS
  Our results indicate that TK-modified MSCs provide enhanced protection against cardiac injury, apoptosis and inflammation, and promote neovascularization after MI, leading to cardiac function improvement.
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Gao
authors.forename: Grant
authors.initials: G
authors.lastname: Bledsoe
authors.forename: Hang
authors.initials: H
authors.lastname: Yin
authors.forename: Bo
authors.initials: B
authors.lastname: Shen
authors.forename: Lee
authors.initials: L
authors.lastname: Chao
authors.forename: Julie
authors.initials: J
authors.lastname: Chao
mesh_terms: D000256:Adenoviridae; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000473:pathology; D009203:Myocardial Infarction / Q000150:complications / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D017202:Myocardial Ischemia / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D018919:Neovascularization, Physiologic; D051381:Rats; D017207:Rats, Sprague-Dawley; D020840:Tissue Kallikreins / Q000096:biosynthesis* / Q000235:genetics; D014161:Transduction, Genetic
chemical_list: D020840:Tissue Kallikreins; C505410:Casp3 protein, rat; D053148:Caspase 3