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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 
Citation
 Cell Transplantation, Vol.22(5) : 797-809 
Journal Title
 Cell Transplantation 
ISSN
 0963-6897 
Issue Date
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
https://ir.ymlib.yonsei.ac.kr/handle/22282913/86904
DOI
10.3727/096368912X656126
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부)
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) > Medical Research Center (임상의학연구센터)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원)
1. Journal Papers (연구논문) > 5. Research Institutes (연구소) > Yonsei Integrative Research Institute for Cerebral & Cardiovascular Disease (뇌심혈관질환융합연구사업단)
Yonsei Authors
김일권(Kim, Il Kwon) ; 박준희(Park, Jun-Hee) ; 송병욱(Song, Byeong Wook) ; 이세연(Lee, Se Yeon) ; 이창연(Lee, Chang Yeon) ; 임소연(Lim, So Yeon) ; 장양수(Jang, Yang Soo) ; 차민지(Cha, Min Ji) ; 최은미(Choi, Eun Mi) ; 최은주(Choi, Eun Ju) ; 함온주(Ham, On Ju) ; 홍범기(Hong, Bum Kee) ; 황기철(Hwang, Ki Chul)
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http://www.ingentaconnect.com/content/cog/ct/2013/00000022/00000005/art00003?token=0051123d42275c277b42572b67527655256f7b2a7942592f653b2a2d3a7c4e724770ff1fa336124e9
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