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Cardiomyocytes from phorbol myristate acetate-activated mesenchymal stem cells restore electromechanical function in infarcted rat hearts

Authors
 Heesang Song  ;  Hye Jin Hwang  ;  Woochul Chang  ;  Byeong-Wook Song  ;  Min-Ji Cha  ;  Il-Kwon Kim  ;  Soyeon Lim  ;  Eun Ju Choi  ;  Onju Ham  ;  Chang Youn Lee  ;  Jun-Hee Park  ;  Se-Yeon Lee  ;  Eunmi Choi  ;  Chungkeun Lee  ;  Myoungho Lee  ;  Moon-Hyoung Lee  ;  Sung-Hou Kim  ;  Yangsoo Jang  ;  Ki-Chul Hwang 
Citation
 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol.108(1) : 296-301, 2011 
Journal Title
 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 
ISSN
 0027-8424 
Issue Date
2011
MeSH
Analysis of Variance ; Animals ; Blotting, Western ; Cell- and Tissue-Based Therapy/methods* ; Connexin 43/metabolism ; Cytokines/immunology ; Electrocardiography ; Enzyme-Linked Immunosorbent Assay ; Fluorescent Antibody Technique ; In Situ Nick-End Labeling ; Isoproterenol/pharmacology ; Male ; Mesenchymal Stem Cell Transplantation/methods ; Mesenchymal Stromal Cells/cytology ; Mesenchymal Stromal Cells/metabolism* ; Myocardial Contraction/drug effects ; Myocardial Contraction/physiology* ; Myocardial Infarction/therapy* ; Myocytes, Cardiac/cytology ; Myocytes, Cardiac/physiology* ; Norepinephrine/metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Adrenergic/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Tetradecanoylphorbol Acetate/metabolism
Keywords
cell therapy ; optical mapping ; differentiation ; heart infarction ; arrhythmia
Abstract
Despite the safety and feasibility of mesenchymal stem cell (MSC) therapy, an optimal cell type has not yet emerged in terms of electromechanical integration in infarcted myocardium. We found that poor to moderate survival benefits of MSC-implanted rats were caused by incomplete electromechanical integration induced by tissue heterogeneity between myocytes and engrafted MSCs in the infarcted myocardium. Here, we report the development of cardiogenic cells from rat MSCs activated by phorbol myristate acetate, a PKC activator, that exhibited high expressions of cardiac-specific markers and Ca(2+) homeostasis-related proteins and showed adrenergic receptor signaling by norepinephrine. Histological analysis showed high connexin 43 coupling, few inflammatory cells, and low fibrotic markers in myocardium implanted with these phorbol myristate acetate-activated MSCs. Infarct hearts implanted with these cells exhibited restoration of conduction velocity through decreased tissue heterogeneity and improved myocardial contractility. These findings have major implications for the development of better cell types for electromechanical integration of cell-based treatment for infarcted myocardium.
Files in This Item:
T201100308.pdf Download
DOI
10.1073/pnas.1015873107/-/DCSupplemental
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Medical Research Center (임상의학연구센터) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kim, Il Kwon(김일권)
Park, Jun-Hee(박준희)
Song, Byeong Wook(송병욱)
Lee, Moon Hyoung(이문형) ORCID logo https://orcid.org/0000-0002-7268-0741
Lee, Se Yeon(이세연)
Lee, Chang Yeon(이창연)
Lee, Chung Keun(이충근)
Lim, So Yeon(임소연)
Jang, Yang Soo(장양수) ORCID logo https://orcid.org/0000-0002-2169-3112
Chang, Woo Chul(장우철)
Cha, Min Ji(차민지)
Choi, Eun Mi(최은미)
Choi, Eun Ju(최은주)
Ham, On Ju(함온주)
Hwang, Ki Chul(황기철)
Hwang, Hye Jin(황혜진)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/92669
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