Document Detail


Myocardial protective effect of extracellular superoxide dismutase gene modified bone marrow mesenchymal stromal cells on infarcted mice hearts.
MedLine Citation:
PMID:  24669277     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
AIM: 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.
METHODS & 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 (2x10(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.
CONCLUSION: 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:
Qiao Pan; Xing Qin; Sai Ma; Haichang Wang; Kang Cheng; Xinxing Song; Haokao Gao; Qiang Wang; Rannie Tao; Yabin Wang; Xiujuan Li; Lize Xiong; Feng Cao
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Publication Detail:
Type:  Journal Article     Date:  2014-02-15
Journal Detail:
Title:  Theranostics     Volume:  4     ISSN:  1838-7640     ISO Abbreviation:  Theranostics     Publication Date:  2014  
Date Detail:
Created Date:  2014-03-26     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101552395     Medline TA:  Theranostics     Country:  Australia    
Other Details:
Languages:  eng     Pagination:  475-86     Citation Subset:  IM    
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