title: Antiarrhythmic potential of mesenchymal stem cell is modulated by hypoxic environment.
abstract: OBJECTIVE
  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.
authors.affiliation: Cardiology Division, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Hwang
authors.forename: Woochul
authors.initials: W
authors.lastname: Chang
authors.forename: Byeong-Wook
authors.initials: BW
authors.lastname: Song
authors.forename: Heesang
authors.initials: H
authors.lastname: Song
authors.forename: Min-Ji
authors.initials: MJ
authors.lastname: Cha
authors.forename: Il-Kwon
authors.initials: IK
authors.lastname: Kim
authors.forename: Soyeon
authors.initials: S
authors.lastname: Lim
authors.forename: Eun Ju
authors.initials: EJ
authors.lastname: Choi
authors.forename: Onju
authors.initials: O
authors.lastname: Ham
authors.forename: Se-Yeon
authors.initials: SY
authors.lastname: Lee
authors.forename: Jaemin
authors.initials: J
authors.lastname: Shim
authors.forename: Boyoung
authors.initials: B
authors.lastname: Joung
authors.forename: Hui-Nam
authors.initials: HN
authors.lastname: Pak
authors.forename: Sung Soon
authors.initials: SS
authors.lastname: Kim
authors.forename: Bum-Rak
authors.initials: BR
authors.lastname: Choi
authors.forename: Yangsoo
authors.initials: Y
authors.lastname: Jang
authors.forename: Moon-Hyoung
authors.initials: MH
authors.lastname: Lee
authors.forename: Ki-Chul
authors.initials: KC
authors.lastname: Hwang
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery*; D004195:Disease Models, Animal; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley