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

Research output: Contribution to journalArticle

155 Citations (Scopus)

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

Fingerprint

Focal Adhesions
Mesenchymal Stromal Cells
Reactive Oxygen Species
Myocardium
Cell Adhesion
Cell-Matrix Junctions
Free Radical Scavengers
Acetylcysteine
Fibronectins
Integrins
Hydrogen Peroxide
Cell Movement
Regeneration
Fibrosis
Myocardial Infarction
Cell Proliferation

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

Cite this

Song, Heesang ; Cha, Min Ji ; Song, Byeong Wook ; Kim, Il Kwon ; Chang, Woochul ; Lim, Soyeon ; Choi, Eun Ju ; Ham, Onju ; Lee, Se Yeon ; Chung, Namsik ; Jang, Yangsoo ; Hwang, Ki Chul. / Reactive oxygen species inhibit adhesion of mesenchymal stem cells implanted into ischemic myocardium via interference of focal adhesion complex. In: Stem Cells. 2010 ; Vol. 28, No. 3. pp. 555-563.
@article{ce13153ed39448c78900c18a9b35928b,
title = "Reactive oxygen species inhibit adhesion of mesenchymal stem cells implanted into ischemic myocardium via interference of focal adhesion complex",
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.",
author = "Heesang Song and Cha, {Min Ji} and Song, {Byeong Wook} and Kim, {Il Kwon} and Woochul Chang and Soyeon Lim and Choi, {Eun Ju} and Onju Ham and Lee, {Se Yeon} and Namsik Chung and Yangsoo Jang and Hwang, {Ki Chul}",
year = "2010",
month = "3",
day = "31",
doi = "10.1002/stem.302",
language = "English",
volume = "28",
pages = "555--563",
journal = "Stem Cells",
issn = "1066-5099",
publisher = "AlphaMed Press",
number = "3",

}

Song, H, Cha, MJ, Song, BW, Kim, IK, Chang, W, Lim, S, Choi, EJ, Ham, O, Lee, SY, Chung, N, Jang, Y & Hwang, KC 2010, 'Reactive oxygen species inhibit adhesion of mesenchymal stem cells implanted into ischemic myocardium via interference of focal adhesion complex', Stem Cells, vol. 28, no. 3, pp. 555-563. https://doi.org/10.1002/stem.302

Reactive oxygen species inhibit adhesion of mesenchymal stem cells implanted into ischemic myocardium via interference of focal adhesion complex. / Song, Heesang; Cha, Min Ji; Song, Byeong Wook; Kim, Il Kwon; Chang, Woochul; Lim, Soyeon; Choi, Eun Ju; Ham, Onju; Lee, Se Yeon; Chung, Namsik; Jang, Yangsoo; Hwang, Ki Chul.

In: Stem Cells, Vol. 28, No. 3, 31.03.2010, p. 555-563.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Reactive oxygen species inhibit adhesion of mesenchymal stem cells implanted into ischemic myocardium via interference of focal adhesion complex

AU - Song, Heesang

AU - Cha, Min Ji

AU - Song, Byeong Wook

AU - Kim, Il Kwon

AU - Chang, Woochul

AU - Lim, Soyeon

AU - Choi, Eun Ju

AU - Ham, Onju

AU - Lee, Se Yeon

AU - Chung, Namsik

AU - Jang, Yangsoo

AU - Hwang, Ki Chul

PY - 2010/3/31

Y1 - 2010/3/31

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=77950564444&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77950564444&partnerID=8YFLogxK

U2 - 10.1002/stem.302

DO - 10.1002/stem.302

M3 - Article

C2 - 20073042

AN - SCOPUS:77950564444

VL - 28

SP - 555

EP - 563

JO - Stem Cells

JF - Stem Cells

SN - 1066-5099

IS - 3

ER -