Reactive Oxygen Species Inhibit Adhesion of Mesenchymal Stem Cells Implanted into Ischemic Myocardium via Interference of Focal Adhesion Complex

• Published in: Stem cells (Dayton, Ohio) Vol. 28; no. 3; pp. 555 - 563
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 31.03.2010
• Subjects: Acetylcysteine - pharmacology; Adhesion; Animals; Cell Adhesion - drug effects; Cell Adhesion - physiology; Cell Adhesion Molecules - drug effects; Cell Adhesion Molecules - metabolism; Cell Differentiation - physiology; Cell Proliferation; Cells, Cultured; Disease Models, Animal; Focal Adhesion Kinase 1 - drug effects; Focal Adhesion Kinase 1 - metabolism; Focal Adhesions - drug effects; Focal Adhesions - metabolism; Free Radical Scavengers - pharmacology; Gene Knock-In Techniques; Graft Survival - physiology; Hydrogen Peroxide - pharmacology; Integrins - drug effects; Integrins - metabolism; Ischemic heart; Male; Mesenchymal Stem Cell Transplantation - methods; Mesenchymal stem cells; Mesenchymal Stromal Cells - metabolism; Myocardial Ischemia - metabolism; Myocardial Ischemia - physiopathology; Myocardial Ischemia - surgery; Oxidants - pharmacology; Oxidative Stress - drug effects; Oxidative Stress - physiology; Rats; Rats, Sprague-Dawley; Reactive oxygen species; Reactive Oxygen Species - metabolism; Regeneration - physiology; src-Family Kinases - drug effects; src-Family Kinases - metabolism; Transplantation
• DOI: 10.1002/stem.302
• ISSN: 1066-5099

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 H2O2 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. STEM CELLS 2010;28:555–563