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

doi:10.1016/j.jacc.2012.04.056

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

Department of Internal Medicine

Research output: Contribution to journal › Article › peer-review

42 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 language	English
Pages (from-to)	1698-1706
Number of pages	9
Journal	Journal of the American College of Cardiology
Volume	60
Issue number	17
DOIs	https://doi.org/10.1016/j.jacc.2012.04.056
Publication status	Published - 2012 Oct 23

Bibliographical note

Funding Information:
This research was supported by a Korea Science and Engineering Foundation (KOSEF) Grant funded by MOST ( M1064102000106N410200110 ), grants from the Stem Cell Research Center of the 21st Century Frontier Research Program ( SC-2150 ) and Basic Science Research Program through the National Research Foundation of Korea ( 7-2011-0267 ) funded by the Ministry of Education, Science, and Technology , and the Korea Health 21 R&D Project, Ministry of Health and Welfare, Republic of Korea ( A085136 ). There was no industry involvement in the study. The authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Hwang, Chang, and Song contributed equally to this work.

All Science Journal Classification (ASJC) codes

Cardiology and Cardiovascular Medicine

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10.1016/j.jacc.2012.04.056

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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

@article{190de885a17e48188327aee3d8ec0147,

title = "Antiarrhythmic potential of mesenchymal stem cell is modulated by hypoxic environment",

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.",

author = "Hwang, {Hye Jin} and Woochul Chang and Song, {Byeong Wook} and Heesang Song and Cha, {Min Ji} and Kim, {Il Kwon} and Soyeon Lim and Choi, {Eun Ju} and Onju Ham and Lee, {Se Yeon} and Jaemin Shim and Boyoung Joung and Pak, {Hui Nam} and Kim, {Sung Soon} and Choi, {Bum Rak} and Yangsoo Jang and Lee, {Moon Hyoung} and Hwang, {Ki Chul}",

note = "Funding Information: This research was supported by a Korea Science and Engineering Foundation (KOSEF) Grant funded by MOST ( M1064102000106N410200110 ), grants from the Stem Cell Research Center of the 21st Century Frontier Research Program ( SC-2150 ) and Basic Science Research Program through the National Research Foundation of Korea ( 7-2011-0267 ) funded by the Ministry of Education, Science, and Technology , and the Korea Health 21 R&D Project, Ministry of Health and Welfare, Republic of Korea ( A085136 ). There was no industry involvement in the study. The authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Hwang, Chang, and Song contributed equally to this work. ",

year = "2012",

month = oct,

day = "23",

doi = "10.1016/j.jacc.2012.04.056",

language = "English",

volume = "60",

pages = "1698--1706",

journal = "Journal of the American College of Cardiology",

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Hwang, HJ, Chang, W, Song, BW, Song, H, Cha, MJ, Kim, IK, Lim, S, Choi, EJ, Ham, O, Lee, SY, Shim, J, Joung, B , Pak, HN, Kim, SS, Choi, BR, Jang, Y, Lee, MH & Hwang, KC 2012, 'Antiarrhythmic potential of mesenchymal stem cell is modulated by hypoxic environment', Journal of the American College of Cardiology, vol. 60, no. 17, pp. 1698-1706. https://doi.org/10.1016/j.jacc.2012.04.056

TY - JOUR

T1 - Antiarrhythmic potential of mesenchymal stem cell is modulated by hypoxic environment

AU - Hwang, Hye Jin

AU - Chang, Woochul

AU - Song, Byeong Wook

AU - Song, Heesang

AU - Cha, Min Ji

AU - Kim, Il Kwon

AU - Lim, Soyeon

AU - Choi, Eun Ju

AU - Ham, Onju

AU - Lee, Se Yeon

AU - Shim, Jaemin

AU - Joung, Boyoung

AU - Pak, Hui Nam

AU - Kim, Sung Soon

AU - Choi, Bum Rak

AU - Jang, Yangsoo

AU - Lee, Moon Hyoung

AU - Hwang, Ki Chul

N1 - Funding Information: This research was supported by a Korea Science and Engineering Foundation (KOSEF) Grant funded by MOST ( M1064102000106N410200110 ), grants from the Stem Cell Research Center of the 21st Century Frontier Research Program ( SC-2150 ) and Basic Science Research Program through the National Research Foundation of Korea ( 7-2011-0267 ) funded by the Ministry of Education, Science, and Technology , and the Korea Health 21 R&D Project, Ministry of Health and Welfare, Republic of Korea ( A085136 ). There was no industry involvement in the study. The authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Hwang, Chang, and Song contributed equally to this work.

PY - 2012/10/23

Y1 - 2012/10/23

N2 - 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.

AB - 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.

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Antiarrhythmic potential of mesenchymal stem cell is modulated by hypoxic environment

Abstract

Bibliographical note

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