title: Cardiomyocytes from phorbol myristate acetate-activated mesenchymal stem cells restore electromechanical function in infarcted rat hearts.
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.
authors.affiliation: Research Institute of Science for Aging, Yonsei University, Seoul 120-752, Korea.
authors.forename: Heesang
authors.initials: H
authors.lastname: Song
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Hwang
authors.forename: Woochul
authors.initials: W
authors.lastname: Chang
authors.forename: Byeong-Wook
authors.initials: BW
authors.lastname: Song
authors.forename: Min-Ji
authors.initials: MJ
authors.lastname: Cha
authors.forename: Il-Kwon
authors.initials: IK
authors.lastname: Kim
authors.forename: Soyeon
authors.initials: S
authors.lastname: Lim
authors.forename: Eun Ju
authors.initials: EJ
authors.lastname: Choi
authors.forename: Onju
authors.initials: O
authors.lastname: Ham
authors.forename: Chang Youn
authors.initials: CY
authors.lastname: Lee
authors.forename: Jun-Hee
authors.initials: JH
authors.lastname: Park
authors.forename: Se-Yeon
authors.initials: SY
authors.lastname: Lee
authors.forename: Eunmi
authors.initials: E
authors.lastname: Choi
authors.forename: Chungkeun
authors.initials: C
authors.lastname: Lee
authors.forename: Myoungho
authors.initials: M
authors.lastname: Lee
authors.forename: Moon-Hyoung
authors.initials: MH
authors.lastname: Lee
authors.forename: Sung-Hou
authors.initials: SH
authors.lastname: Kim
authors.forename: Yangsoo
authors.initials: Y
authors.lastname: Jang
authors.forename: Ki-Chul
authors.initials: KC
authors.lastname: Hwang
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D018031:Connexin 43 / Q000378:metabolism; D016207:Cytokines / Q000276:immunology; D004562:Electrocardiography; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D020287:In Situ Nick-End Labeling; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D009203:Myocardial Infarction / Q000628:therapy*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000502:physiology*; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011941:Receptors, Adrenergic / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013755:Tetradecanoylphorbol Acetate / Q000378:metabolism
chemical_list: D018031:Connexin 43; D016207:Cytokines; D011941:Receptors, Adrenergic; D007545:Isoproterenol; D013755:Tetradecanoylphorbol Acetate; D009638:Norepinephrine