title: Myocardial protective effect of extracellular superoxide dismutase gene modified bone marrow mesenchymal stromal cells on infarcted mice hearts.
abstract: OBJECTIVE
  Extracellular superoxide dismutase (ecSOD) is a unique scavenger of superoxide anions and a promising target of gene therapy for ischemia/reperfusion injury (I/R). However, conventional gene therapies have limitation in effectiveness and efficiency. This study aimed to investigate the protective effects of ecSOD gene modified bone marrow mesenchymal stromal cells (BMSCs) on cardiac function improvement in mice infarcted heart.
  
  
  RESULTS
  BMSCs were isolated from Fluc(+) transgenic mice (Tg FVB[Fluc(+)]) and transfected by adenovirus combined with human ecSOD gene. ELISA was performed to determine ecSOD protein level. Female syngeneic FVB mice were randomized into 5 groups: (1) Sham group (sham); (2) MI group (MI); (3) MI+BMSCs group (BMSC); (4) MI+BMSCs-vector group (BMSC-vector); (5) MI+ BMSCs-ecSOD group (BMSC-ecSOD). MI was accomplished by ligation of the left anterior descending artery. BMSCs (2 x 10(6)) were injected into the border zone of infarction. In vivo bioluminescence imaging (BLI) was performed to monitor transplanted BMSCs viability. Echocardiography and histological staining revealed that BMSCs-ecSOD significantly reduced myocardial infarction size and improved cardiac function. Lucigenin chemiluminescence, DHE and TUNEL staining demonstrated that BMSCs-ecSOD delivery reduced ROS level and cell apoptosis both in vivo and in vitro. Western blot assay revealed that ecSOD supplementation increased FoxO3a phosphorylation in cardiomyocytes. Moreover, quantitative real-time PCR showed that pro-apoptotic factors (bim and bax) were decreased while the anti-apoptotic factor mir-21 expression was increased after ecSOD intervention.
  
  
  CONCLUSIONS
  Intra-myocardial transplantation of adenovirus-ecSOD transfected BMSCs could exert potential cardiac protection against MI, which may be partly through reduction of oxidative stress and improvement of BMSCs survival.
authors.affiliation: 1. Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China;
authors.forename: Qiao
authors.initials: Q
authors.lastname: Pan
authors.affiliation: 1. Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China;
authors.forename: Xing
authors.initials: X
authors.lastname: Qin
authors.affiliation: 1. Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China;
authors.forename: Sai
authors.initials: S
authors.lastname: Ma
authors.affiliation: 1. Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China;
authors.forename: Haichang
authors.initials: H
authors.lastname: Wang
authors.affiliation: 1. Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China;
authors.forename: Kang
authors.initials: K
authors.lastname: Cheng
authors.affiliation: 1. Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China;
authors.forename: Xinxing
authors.initials: X
authors.lastname: Song
authors.affiliation: 1. Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China;
authors.forename: Haokao
authors.initials: H
authors.lastname: Gao
authors.affiliation: 2. Department of Anesthesia, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China;
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.affiliation: 3. Department of Medicine & Dentistry, University of Alberta, Canada;
authors.forename: Rannie
authors.initials: R
authors.lastname: Tao
authors.affiliation: 1. Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China;
authors.forename: Yabin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 1. Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China;
authors.forename: Xiujuan
authors.initials: X
authors.lastname: Li
authors.affiliation: 2. Department of Anesthesia, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China;
authors.forename: Lize
authors.initials: L
authors.lastname: Xiong
authors.affiliation: 1. Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China; ; 4. Department of Cardiology, China PLA General Hospital, Beijing 100853, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Cao
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000201:enzymology*; D051379:Mice; D009203:Myocardial Infarction / Q000628:therapy*; D011897:Random Allocation; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D013482:Superoxide Dismutase
keywords: cell-based gene therapy; human extracellular superoxide dismutase; mesenchymal stromal cells; myocardial infarction; reactive oxygen species.