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Tissue transglutaminase is essential for integrin-mediated survival of bone marrow-derived mesenchymal stem cells

 Heesang Song  ;  Woochul Chang  ;  Ki-Chul Hwang  ;  Namsik Chung  ;  Yangsoo Jang  ;  Hakbae Lee  ;  Byoung-Hyun Min  ;  Byung-Soo Kim  ;  Kyung-Jong Yoo  ;  Sungha Park  ;  Chi Young Shim  ;  Hye-Sun Seo  ;  Soyeon Lim 
 Stem Cells, Vol.25(6) : 1431-1438, 2007 
Journal Title
 Stem Cells 
Issue Date
Autologous mesenchymal stem cell (MSC) transplantation therapy for repair of myocardial injury has inherent limitations due to the poor viability of the stem cells after cell transplantation. Adhesion is a prerequisite for cell survival and also a key factor for the differentiation of MSCs. As a novel prosurvival modification strategy, we genetically engineered MSCs to overexpress tissue transglutaminase (tTG), with intention to enhance adhesion and ultimately cell survival after implantation. tTG-transfected MSCs (tTG-MSCs) showed a 2.7-fold and greater than a twofold increase of tTG expression and surface tTG activity, respectively, leading to a 20% increased adhesion of MSCs on fibronectin (Fn). Spreading and migration of tTG-MSCs were increased 4.75% and 2.52%, respectively. Adhesion of tTG-MSCs on cardiogel, a cardiac fibroblast-derived three-dimensional matrix, showed a 33.1% increase. Downregulation of tTG by transfection of small interfering RNA specific to the tTG resulted in markedly decreased adhesion and spread of MSCs on Fn or cardiogel. tTG-MSCs on Fn significantly increased phosphorylation of focal adhesion related kinases FAK, Src, and PI3K. tTG-MSCs showed significant retention in infarcted myocardium by forming a focal adhesion complex and developed into cardiac myocyte-like cells by the expression of cardiac-specific proteins. Transplantation of 1 × 106 MSCs transduced with tTG into the ischemic rat myocardium restored normalized systolic and diastolic cardiac function. tTG-MSCs further restored cardiac function of infarcted myocardium as compared with MSC transplantation alone. These findings suggested that tTG may play an important role in integrin-mediated adhesion of MSCs in implanted tissues.
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1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Medical Research Center (임상의학연구센터)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Thoracic and Cardiovascular Surgery (흉부외과학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부)
Yonsei Authors
박성하(Park, Sung Ha) ORCID logo https://orcid.org/0000-0001-5362-478X
서혜선(Seo, Hye Sun)
심지영(Shim, Chi Young) ORCID logo https://orcid.org/0000-0002-6136-0136
유경종(Yoo, Kyung Jong) ORCID logo https://orcid.org/0000-0002-9858-140X
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)
황기철(Hwang, Ki Chul)
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