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Reactive oxygen species inhibit adhesion of mesenchymal stem cells implanted into ischemic myocardium via interference of focal adhesion complex.

Authors
 HEESANG SONG  ;  MIN-JI CHA  ;  BYEONG-WOOK SONG  ;  IL-KWON KIM  ;  WOOCHUL CHANG  ;  SOYEON LIM  ;  EUN JU CHOI  ;  ONJU HAM  ;  SE-YEON LEE  ;  NAMSIK CHUNG  ;  YANGSOO JANG  ;  KI-CHUL HWANG 
Citation
 Stem Cells, Vol.28(3) : 555-563, 2010 
Journal Title
 Stem Cells 
ISSN
 1066-5099 
Issue Date
2010
Abstract
The integrity of transplanted mesenchymal stem cells (MSCs) for cardiac regeneration is dependent on cell-cell or cell-matrix adhesion, which is inhibited by reactive oxygen species (ROS) generated in ischemic surroundings after myocardial infarction. Intracellular ROS play a key role in the regulation of cell adhesion, migration, and proliferation. This study was designed to investigate the role of ROS on MSC adhesion. In H(2)O(2) treated MSCs, adhesion and spreading were inhibited and detachment was increased in a dose-dependent manner, and these effects were significantly rescued by co-treatment with the free radical scavenger, N-acetyl-L-cysteine (NAC, 1 mM). A similar pattern was observed on plates coated with different matrices such as fibronectin and cardiogel. Hydrogen peroxide treatment resulted in a marked decrease in the level of focal adhesion-related molecules, such as phospho-FAK and p-Src in MSCs. We also observed a significant decrease in the integrin-related adhesion molecules, alpha V and beta1, in H(2)O(2) treated MSCs. When injected into infarcted hearts, the adhesion of MSCs co-injected with NAC to the border region was significantly improved. Consequently, we observed that fibrosis and infarct size were reduced in MSC and NAC-injected rat hearts compared to in MSC-only injected hearts. These results indicate that ROS inhibit cellular adhesion of engrafted MSCs and provide evidence that the elimination of ROS might be a novel strategy for improving the survival of engrafted MSCs
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DOI
10.1002/stem.302
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Medical Research Center (임상의학연구센터)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부)
Yonsei Authors
김일권(Kim, Il Kwon)
송병욱(Song, Byeong Wook)
이세연(Lee, Se Yeon)
임소연(Lim, So Yeon)
장양수(Jang, Yang Soo) ORCID logo https://orcid.org/0000-0002-2169-3112
장우철(Chang, Woo Chul)
정남식(Chung, Nam Sik)
차민지(Cha, Min Ji)
최은주(Choi, Eun Ju)
함온주(Ham, On Ju)
황기철(Hwang, Ki Chul)
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/100822
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