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

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

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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 H2O2 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, αV and β1, in H 2O2 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.

Original languageEnglish
Pages (from-to)555-563
Number of pages9
JournalStem Cells
Volume28
Issue number3
DOIs
Publication statusPublished - 2010 Mar 31

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

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    Song, H., Cha, M. J., Song, B. W., Kim, I. K., Chang, W., Lim, S., Choi, E. J., Ham, O., Lee, S. Y., Chung, N., Jang, Y., & Hwang, K. C. (2010). Reactive oxygen species inhibit adhesion of mesenchymal stem cells implanted into ischemic myocardium via interference of focal adhesion complex. Stem Cells, 28(3), 555-563. https://doi.org/10.1002/stem.302