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Hypoxia-inducible vascular endothelial growth factor-engineered mesenchymal stem cells prevent myocardial ischemic injury

Authors
 Sun Hwa Kim  ;  Hyung-Ho Moon  ;  Donghoon Choi  ;  Minhyung Lee  ;  Ki-Chul Hwang  ;  Hyun Ah Kim 
Citation
 Molecular Therapy, Vol.19(4) : 741-750, 2011 
Journal Title
 Molecular Therapy 
ISSN
 1525-0016 
Issue Date
2011
Abstract
In the absence of repair mechanisms involving angiogenesis and cardiomyogenesis, loss of cardiomyocytes after myocardial injury is a primary causative factor in the progression toward heart failure. In an effort to reduce ischemic myocardial damage, we investigated the effects on infarcted myocardium of transplantation of genetically modified mesenchymal stem cells (MSCs) that specifically expressed vascular endothelial growth factor (VEGF) under hypoxic conditions. A hypoxia-inducible VEGF expression vector was introduced into MSCs (HI-VEGF-MSCs) using a nonviral delivery method, which were then used for the treatment of ischemic myocardial injury in rats. In HI-VEGF-MSCs, VEGF expression was significantly increased by hypoxia in vitro as compared to normoxia. Likewise, in vivo administration of HI-VEGF-MSCs induced ischemia-responsive VEGF production, leading to a significant increase in myocardial neovascularization after myocardial infarction. When compared with unmodified-MSCs, HI-VEGF-MSCs were retained in infarcted myocardium in greater numbers and remarkably reduced the number of apoptotic cells the infarcted area. Transplantation of HI-VEGF-MSCs resulted in a substantial attenuation of left ventricular remodeling in rat myocardial infarction. This study demonstrates that cell-based gene therapy using genetically engineered MSCs to express VEGF in response to hypoxic stress can be a promising therapeutic strategy for the treatment of ischemic heart disease.
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/93278
DOI
10.1038/mt.2010.301
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Life Science (의생명과학부)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원)
1. Journal Papers (연구논문) > 5. Research Institutes (연구소) > Yonsei Integrative Research Institute for Cerebral & Cardiovascular Disease (뇌심혈관질환융합연구사업단)
Yonsei Authors
김선화(Kim, Sun Hwa) ; 문형호(Moon, Hyung Ho) ; 최동훈(Choi, Dong Hoon) ; 황기철(Hwang, Ki Chul)
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