Protein Kinase C Activation Stimulates Mesenchymal Stem Cell Adhesion through Activation of Focal Adhesion Kinase

Author:

Song Byeong-Wook12,Chang Woochul3,Hong Bum-Kee4,Kim Il-Kwon12,Cha Min-Ji12,Lim Soyeon5,Choi Eun Ju12,Ham Onju12,Lee Se-Yeon12,Lee Chang Youn6,Park Jun-Hee6,Choi Eunmi7,Song Heesang8,Jang Yangsoo19,Hwang Ki-Chul127

Affiliation:

1. Cardiovascular Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea

2. Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea

3. Institute of Catholic Integrative Medicine, Incheon St. Mary's Hospital, The Catholic University of Korea College of Medicine, Incheon, Republic of Korea

4. Heart Center, Gangnam Severance Hospital, Seoul, Republic of Korea

5. Severance Integrative Research Institute for Cerebral and Cardiovascular Disease, Yonsei University Health System, Seoul, Republic of Korea

6. Department of Integrated Omics for Biomedical Sciences, Graduate School, Yonsei University, Seoul, Republic of Korea

7. Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Republic of Korea

8. Department of Biochemistry and Molecular Biology, Chosun University School of Medicine, Gwangju, Republic of Korea

9. Cardiology Division, Yonsei University College of Medicine, Seoul, Republic of Korea

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.

Publisher

SAGE Publications

Subject

Transplantation,Cell Biology,Biomedical Engineering

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3