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Antiarrhythmic potential of mesenchymal stem cell is modulated by hypoxic environment.

 Hye Jin Hwang  ;  Woochul Chang  ;  Byeong-Wook Song  ;  Heesang Song  ;  Min-Ji Cha  ;  Il-Kwon Kim  ;  Soyeon Lim  ;  Eun Ju Choi  ;  Onju Ham  ;  Se-Yeon Lee  ;  Jaemin Shim  ;  Boyoung Joung  ;  Hui-Nam Pak  ;  Sung Soon Kim  ;  Bum-Rak Choi  ;  Yangsoo Jang  ;  Moon-Hyoung Lee  ;  Ki-Chul Hwang 
 Journal of the American College of Cardiology, Vol.60(17) : 1698-1706, 2012 
Journal Title
 Journal of the American College of Cardiology 
Issue Date
Animals ; Arrhythmias, Cardiac/metabolism ; Arrhythmias, Cardiac/physiopathology ; Arrhythmias, Cardiac/surgery* ; Disease Models, Animal ; Hypoxia/metabolism ; Hypoxia/physiopathology ; Hypoxia/therapy* ; Male ; Mesenchymal Stem Cell Transplantation/methods* ; Myocardium/metabolism* ; Myocardium/pathology ; Rats ; Rats, Sprague-Dawley
arrhythmia ; mesenchymal stem cells ; myocardial infarction ; paracrine factors
OBJECTIVES: The purpose of this study was to evaluate the antiarrhythmic potential of mesenchymal stem cells (MSC) under a different environment. BACKGROUND: Little is known about how environmental status affects antiarrhythmic potential of MSCs. METHODS: To investigate the effect of paracrine factors secreted from MSCs under different circumstances on arrhythmogenicity in rats with myocardial infarction, we injected paracrine media (PM) secreted under hypoxic, normoxic conditions (hypoxic PM and normoxic PM), and MSC into the border zone of infarcted myocardium in rats. RESULTS: We found that the injection of hypoxic PM, but not normoxic PM, markedly restored conduction velocities, suppressed focal activity, and prevented sudden arrhythmic deaths in rats. Underlying this electrophysiological alteration was a decrease in fibrosis, restoration of connexin 43, alleviation of Ca(2+) overload, and recovery of Ca(2+)-regulatory ion channels and proteins, all of which is supported by proteomic data showing that several paracrine factors including basic fibroblast growth factor, insulinlike growth factor 1, hepatocyte growth factor, and EF-hand domain-containing 2 are potential mediators. When compared with PM, MSC injection did not reduce or prevent arrhythmogenicity, suggesting that the antiarrhythmic or proarrhythmic potential of MSC is mainly dependent on paracrine factors. CONCLUSIONS: A hypoxic or normoxic environment surrounding MSC affects the type and properties of the growth factors or cytokines, and these secreted molecules determine the characteristics of the electro-anatomical substrate of the surrounding myocardium.
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Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
5. Research Institutes (연구소) > Yonsei Integrative Research Institute for Cerebral & Cardiovascular Disease (뇌심혈관질환융합연구사업단) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Medical Research Center (임상의학연구센터) > 1. Journal Papers
Yonsei Authors
Kim, Sung Soon(김성순)
Kim, Il Kwon(김일권)
Pak, Hui Nam(박희남) ORCID logo https://orcid.org/0000-0002-3256-3620
Song, Byeong Wook(송병욱)
Shim, Jae Min(심재민)
Lee, Moon Hyoung(이문형) ORCID logo https://orcid.org/0000-0002-7268-0741
Lee, Se Yeon(이세연)
Lim, So Yeon(임소연)
Jang, Yang Soo(장양수) ORCID logo https://orcid.org/0000-0002-2169-3112
Joung, Bo Young(정보영) ORCID logo https://orcid.org/0000-0001-9036-7225
Cha, Min Ji(차민지)
Choi, Eun Ju(최은주)
Ham, On Ju(함온주)
Hwang, Ki Chul(황기철)
Hwang, Hye Jin(황혜진)
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