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Title: Differential effect of myocardial matrix and integrins on cardiac differentiation of human mesenchymal stem cells
Authors: Tan, G.
Shim, W.
Gu, Y.
Qian, L.
Ying Chung, Y.
Yun Lim, S.
Yong, P.
Sim, E. 
Wong, P.
Keywords: Cardiomyogenesis
Extracellular matrix
Myocardial infarction
Stem cells
Issue Date: Apr-2010
Citation: Tan, G., Shim, W., Gu, Y., Qian, L., Ying Chung, Y., Yun Lim, S., Yong, P., Sim, E., Wong, P. (2010-04). Differential effect of myocardial matrix and integrins on cardiac differentiation of human mesenchymal stem cells. Differentiation 79 (4-5) : 260-271. ScholarBank@NUS Repository.
Abstract: Dysregulation of matrix synthesis during myocardial fibrosis in post-infarct ventricular remodeling contributes to ventricular dysfunction. Bone marrow stem cell transplantation prevents functional deterioration following myocardial infarction. However, effect of myocardial extracellular matrix (ECM) on stem cell differentiation is poorly understood. We investigate the role of collagen matrices and integrin system in cardiac differentiation and engraftment of stem cells in infarcted myocardium. Sternum-derived bone marrow mesenchymal stem cells (MSCs) were differentiated into cardiomyocyte-like cells (CLCs). They were characterized using RT-PCR, immunofluorescence, flow cytometry and functional integrin neutralization assays. CLCs were injected into peri-infarct borders of injured myocardium of Wistar rats one week following left anterior descending (LAD) artery ligation. Cardiac function was analyzed via pressure-volume relationships. Cardiac differentiated CLCs displayed collagen V specificity, which was absent in undifferentiated MSCs. Collagen V, but not collagen I matrix, promoted attachment, proliferation and cardiac differentiation of CLCs. In contrast to Β1, αv integrin contributed minimally in the attachment of CLCs on collagen matrices. However, inhibition of αvΒ3, but not α2Β1 integrin, selectively attenuated troponin T, sarcomeric α-actin and ryanodine 2 receptor gene expression in CLCs. Both MSC and CLC transplantation prevented chamber dilatation and improved contractile function. However, systolic activity in MSC transplanted animals was accompanied by heightened wall stress as demonstrated by elevated myocardial end-diastolic pressure and prolonged tissue relaxation time. Localization of CLCs in the vicinity of collagen V-expressing myofibers promoted their integration into cardiac syncytium. CLCs may facilitate hemodynamic recovery by preserving tissue elasticity in the peri-infarct borders that sustains contractile efficiency for functional recovery in an actively remodeling infarcted myocardium. © 2010.
Source Title: Differentiation
ISSN: 03014681
DOI: 10.1016/j.diff.2010.02.005
Appears in Collections:Staff Publications

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