title: Transplantation of SIRT1-engineered aged mesenchymal stem cells improves cardiac function in a rat myocardial infarction model.
abstract: BACKGROUND
  Previous studies have demonstrated that biological aging has a negative influence on the therapeutic effects of mesenchymal stem cells (MSCs)-based therapy. Using a rat myocardial infarction (MI) model, we tested the hypothesis that silent mating type information regulation 2 homolog 1 (SIRT1) may ameliorate the phenotype and improve the function of aged MSCs and thus enhance the efficacy of aged MSCs-based therapy.
  
  
  METHODS
  Sixty female rats underwent left anterior descending coronary artery ligation and were randomly assigned to receiving: intramyocardial injection of cell culture medium (DMEM group); SIRT1 overexpression vector-treated aged MSCs (SIRT1-aged MSCs group) obtained from aged male SD rats or empty vector-treated aged MSCs (vector-aged MSCs group). Another 20 sham-operated rats that underwent open-chest surgery without coronary ligation or any other intervention served as controls.
  
  
  RESULTS
  SIRT1-aged MSC group exhibited enhanced blood vessel density in the border zone of MI hearts, which was associated with reduced cardiac remodeling, leading to improved cardiac performance. Consistent with the in vivo data, our in vitro experiments also demonstrated that SIRT1 overexpression ameliorated aged MSCs senescent phenotype and recapitulated the pro-angiogenesis property of MSCs and conferred the anti-stress response capabilities, as indicated by increases in pro-angiogenic factors, angiopoietin 1 (Ang1) and basic fibroblast growth factor (bFGF), expressions and a decrease in anti-angiogenic factor thrombospondin-1 (TBS1) at mRNA levels, and increases in Bcl-2/Bax ratio at protein level.
  
  
  CONCLUSIONS
  Up-regulating SIRT1 expression could enhance the efficacy of aged MSCs-based therapy for MI as it relates to the amelioration of senescent phenotype and hence improved biological function of aged MSCs.
authors.affiliation: Department of Cardiology, Key Division of Ministry of Health, Zhejiang University School of Medicine, Hangzhou, China; Provincial Key Laboratory of Cardiovascular Research, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Xianbao
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Key Division of Ministry of Health, Zhejiang University School of Medicine, Hangzhou, China; Provincial Key Laboratory of Cardiovascular Research, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Huiqiang
authors.initials: H
authors.lastname: Chen
authors.affiliation: Provincial Key Laboratory of Cardiovascular Research, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Department of Cardiology, Key Division of Ministry of Health, Zhejiang University School of Medicine, Hangzhou, China; Provincial Key Laboratory of Cardiovascular Research, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Han
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Key Division of Ministry of Health, Zhejiang University School of Medicine, Hangzhou, China; Provincial Key Laboratory of Cardiovascular Research, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Xinyang
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Cardiology, Key Division of Ministry of Health, Zhejiang University School of Medicine, Hangzhou, China; Provincial Key Laboratory of Cardiovascular Research, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: Department of Cardiology, Key Division of Ministry of Health, Zhejiang University School of Medicine, Hangzhou, China; Provincial Key Laboratory of Cardiovascular Research, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Yinchuan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Cardiology, Key Division of Ministry of Health, Zhejiang University School of Medicine, Hangzhou, China; Provincial Key Laboratory of Cardiovascular Research, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Cardiology, Key Division of Ministry of Health, Zhejiang University School of Medicine, Hangzhou, China; Provincial Key Laboratory of Cardiovascular Research, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Kan
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Key Division of Ministry of Health, Zhejiang University School of Medicine, Hangzhou, China; Provincial Key Laboratory of Cardiovascular Research, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Lihan
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Key Division of Ministry of Health, Zhejiang University School of Medicine, Hangzhou, China; Provincial Key Laboratory of Cardiovascular Research, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Panpan
authors.initials: P
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Key Division of Ministry of Health, Zhejiang University School of Medicine, Hangzhou, China; Provincial Key Laboratory of Cardiovascular Research, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Hengxun
authors.initials: H
authors.lastname: Hu
authors.affiliation: Department of Cardiology, Key Division of Ministry of Health, Zhejiang University School of Medicine, Hangzhou, China; Provincial Key Laboratory of Cardiovascular Research, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Key Division of Ministry of Health, Zhejiang University School of Medicine, Hangzhou, China; Provincial Key Laboratory of Cardiovascular Research, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Na
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Key Division of Ministry of Health, Zhejiang University School of Medicine, Hangzhou, China; Provincial Key Laboratory of Cardiovascular Research, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Qunchao
authors.initials: Q
authors.lastname: Ma
authors.affiliation: Department of Cardiology, Key Division of Ministry of Health, Zhejiang University School of Medicine, Hangzhou, China; Provincial Key Laboratory of Cardiovascular Research, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Mingyuan
authors.initials: M
authors.lastname: Huang
authors.affiliation: Department of Cardiology, Key Division of Ministry of Health, Zhejiang University School of Medicine, Hangzhou, China; Provincial Key Laboratory of Cardiovascular Research, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Dexing
authors.initials: D
authors.lastname: Hu
authors.affiliation: Provincial Key Laboratory of Cardiovascular Research, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Provincial Key Laboratory of Cardiovascular Research, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Rongrong
authors.initials: R
authors.lastname: Wu
authors.affiliation: Department of Cardiology, Key Division of Ministry of Health, Zhejiang University School of Medicine, Hangzhou, China; Provincial Key Laboratory of Cardiovascular Research, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Key Division of Ministry of Health, Zhejiang University School of Medicine, Hangzhou, China; Provincial Key Laboratory of Cardiovascular Research, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Qiyuan
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Provincial Key Laboratory of Cardiovascular Research, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Cardiology, Key Division of Ministry of Health, Zhejiang University School of Medicine, Hangzhou, China; Provincial Key Laboratory of Cardiovascular Research, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. Electronic address: jian_an_wang@yahoo.com.
authors.forename: Jian'an
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000502:physiology*; D004195:Disease Models, Animal; D004452:Echocardiography; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D006321:Heart / Q000502:physiology*; D006439:Hemodynamics / Q000502:physiology; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D009203:Myocardial Infarction / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D010641:Phenotype; D051381:Rats; D017207:Rats, Sprague-Dawley; D012259:Ribonuclease, Pancreatic / Q000378:metabolism; D056564:Sirtuin 1 / Q000502:physiology*; D016896:Treatment Outcome; D015854:Up-Regulation / Q000502:physiology*
chemical_list: D015415:Biomarkers; D016222:Fibroblast Growth Factor 2; C046366:angiogenin; D012259:Ribonuclease, Pancreatic; C488368:Sirt1 protein, rat; D056564:Sirtuin 1
keywords: SIRT1; aging; mesenchymal stem cells; myocardial infarction; stem cell therapy