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

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

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 Ca2+-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.

Original languageEnglish
Pages (from-to)1698-1706
Number of pages9
JournalJournal of the American College of Cardiology
Volume60
Issue number17
DOIs
Publication statusPublished - 2012 Oct 23
Externally publishedYes

Keywords

  • arrhythmia
  • mesenchymal stem cells
  • myocardial infarction
  • paracrine factors

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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  • Cite this

    Hwang, H. J., Chang, W., Song, B. W., Song, H., Cha, M. J., Kim, I. K., Lim, S., Choi, E. J., Ham, O., Lee, S. Y., Shim, J., Joung, B., Pak, H. N., Kim, S. S., Choi, B. R., Jang, Y., Lee, M. H., & Hwang, K. C. (2012). Antiarrhythmic potential of mesenchymal stem cell is modulated by hypoxic environment. Journal of the American College of Cardiology, 60(17), 1698-1706. https://doi.org/10.1016/j.jacc.2012.04.056