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Protein Kinase C activation stimulates mesenchymal stem cell adhesion through activation of focal adhesion kinase

Title
Protein Kinase C activation stimulates mesenchymal stem cell adhesion through activation of focal adhesion kinase
Authors
Song, Byeong-Wook;Chang, Woochul;Hwang, Ki-Chul;Jang, Yangsoo;Song, Heesang;Choi, Eunmi;Park, Jun-Hee;Lee, Chang Youn;Lee, Se-Yeon;Ham, Onju;Choi, Eun Ju;Lim, Soyeon;Cha, Min-Ji;Kim, Il-Kwon;Hong, Bum-Kee
Issue Date
2013
Journal Title
Cell Transplantation
ISSN
0963-6897
Citation
Cell Transplantation, Vol.22(5) : 797~809, 2013
Abstract
Emerging evidence suggests that cell therapy with mesenchymal stem cells (MSCs) has beneficial effects on the injured heart. However, the decreased survival and/or adhesion of MSCs under ischemic conditions limits the application of cell transplantation as a therapeutic modality. We investigated a potential method of increasing the adhesion ability of MSCs to improve their efficacy in the ischemic heart. Treatment of MSCs with PKC activator, phorbol 12-myristate 13-acetate (PMA), increased cell adhesion and spreading in a dose-dependent method and significantly decreased detachment. When MSCs were treated with PKC inhibitor, that is, rottlerin, adhesion of MSCs was slightly diminished, and detachment was also decreased compared to the treatment with PMA. MSCs treated with both PMA and rottlerin behaved similarly to normal controls. In 3D matrix cardiogel, treatment with PMA increased the number of MSCs compared to the control group and MSCs treated with rottlerin. Expressions of focal adhesion kinase, cytoskeleton-associated proteins, and integrin subunits were clearly demonstrated in PMA-treated MSCs by immunoblotting and/or immunocytochemistry. The effect of PKC activator treatment on MSCs was validated in vivo. Following injection into rat hearts, the PMA-treated MSCs exhibited significantly higher retention in infarcted myocardium compared to the MSC group. Infarct size, fibrosis area, and apoptotic cells were reduced, and cardiac function was improved in rat hearts injected with PMA-treated MSCs compared to sham and/or MSC-implanted group. These results indicate that PKC activator is a potential target for niche manipulation to enhance adhesion of MSCs for cardiac regeneration.
URI
http://www.ingentaconnect.com/content/cog/ct/2013/00000022/00000005/art00003?token=0051123d42275c277b42572b67527655256f7b2a7942592f653b2a2d3a7c4e724770ff1fa336124e9

http://ir.ymlib.yonsei.ac.kr/handle/22282913/86904
DOI
10.3727/096368912X656126
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Dept. of Life Science
1. 연구논문 > 1. College of Medicine > Dept. of Thoracic & Cardiovascular Surgery
1. 연구논문 > 1. College of Medicine > Medical Research Center
1. 연구논문 > 1. College of Medicine > Dept. of Internal Medicine
1. 연구논문 > 1. College of Medicine > Yonsei Biomedical Research Center
1. 연구논문 > 5. Research Institutes > Yonsei Integrative Research Institute for Cerebral & Cardiovascular Disease
Yonsei Authors
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