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

 Song, Byeong-Wook  ;  Chang, Woochul  ;  Hong, Bum-Kee  ;  Kim, Il-Kwon  ;  Cha, Min-Ji  ;  Lim, Soyeon  ;  Choi, Eun Ju  ;  Ham, Onju  ;  Lee, Se-Yeon  ;  Lee, Chang Youn  ;  Park, Jun-Hee  ;  Choi, Eunmi  ;  Song, Heesang  ;  Jang, Yangsoo  ;  Hwang, Ki-Chul 
 CELL TRANSPLANTATION, Vol.22(5) : 797-809, 2013 
Journal Title
Issue Date
Acetophenones/pharmacology ; Animals ; Benzopyrans/pharmacology ; Cell Adhesion/drug effects ; Focal Adhesion Protein-Tyrosine Kinases/metabolism* ; Integrins/metabolism ; Male ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells/cytology* ; Myocardial Ischemia/therapy ; Myocardium/pathology ; Protein Kinase C/antagonists & inhibitors ; Protein Kinase C/chemistry ; Protein Kinase C/metabolism* ; Rats ; Rats, Sprague-Dawley ; Tetradecanoylphorbol Acetate/analogs & derivatives ; Tetradecanoylphorbol Acetate/pharmacology ; rho GTP-Binding Proteins/metabolism
Adhesion ; Ischemic heart ; Mesenchymal stem cells (MSCs) ; Protein kinase C (PKC) ; Transplantation
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.
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Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Thoracic and Cardiovascular Surgery (흉부외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Medical Research Center (임상의학연구센터) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
5. Research Institutes (연구소) > Yonsei Integrative Research Institute for Cerebral & Cardiovascular Disease (뇌심혈관질환융합연구사업단) > 1. Journal Papers
Yonsei Authors
Kim, Il Kwon(김일권)
Park, Jun-Hee(박준희)
Song, Byeong Wook(송병욱)
Lee, Se Yeon(이세연)
Lee, Chang Yeon(이창연)
Lim, So Yeon(임소연)
Jang, Yang Soo(장양수) ORCID logo https://orcid.org/0000-0002-2169-3112
Cha, Min Ji(차민지)
Choi, Eun Mi(최은미)
Choi, Eun Ju(최은주)
Ham, On Ju(함온주)
Hong, Bum Kee(홍범기) ORCID logo https://orcid.org/0000-0002-6456-0184
Hwang, Ki Chul(황기철)
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