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

Authors
Song, H; Chang, W; Lim, S; Seo, HS; Shim, CY; Park, S; Yoo, KJ; Kim, BS; Min, BH; Lee, H; Jang, Y; Chung, N; Hwang, KC
Citation
Stem cells, 25(6):1431-1438, 2007
Journal Title
Stem cells
ISSN
0250-6793
Abstract
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 x 10(6) 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. Disclosure of potential conflicts of interest is found at the end of this article.
MeSH terms
AnimalsBone Marrow Cells/cytology*Bone Marrow Cells/metabolismCell Adhesion/geneticsCell Movement/geneticsCell ProliferationCell SurvivalCells, CulturedGTP-Binding Proteins/geneticsGTP-Binding Proteins/metabolismGTP-Binding Proteins/physiology*Heart/physiologyIntegrins/physiology*MaleMesenchymal Stem Cell TransplantationMesenchymal Stem Cells/cytology*Mesenchymal Stem Cells/metabolismRatsRats, Sprague-DawleyTransfectionTransglutaminases/geneticsTransglutaminases/metabolismTransglutaminases/physiology*
DOI
10.1634/stemcells.2006-0467
PMID
17347495
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Journal Papers > School of Medicine / Graduate School of Medicine > Orthopedic Surgery
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