Xu, Ruodan, Srinivasan, Sureshkumar Perumal, Sureshkumar, Poornima, Nembo, Erastus Nembu, Schaefer, Christoph, Semmler, Judith, Matzkiesb, Matthias, Albrechtsena, Morten, Hescheler, Juergen and Nguemo, Filomain (2015). Effects of Synthetic Neural Adhesion Molecule Mimetic Peptides and Related Proteins on the Cardiomyogenic Differentiation of Mouse Embryonic Stem Cells. Cell. Physiol. Biochem., 35 (6). S. 2437 - 2451. BASEL: KARGER. ISSN 1421-9778

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Abstract

Background/Aims: Pluripotent stem cells differentiating into cardiomyocyte-like cells in an appropriate cellular environment have attracted significant attention, given the potential use of such cells for regenerative medicine. However, the precise mechanisms of lineage specification of pluripotent stem cells are still largely to be explored. Identifying the role of various small synthetic peptides involved in cardiomyogenesis may provide new insights into pathways promoting cardiomyogenesis. Methods: In the present study, using a transgenic murine embryonic stem (ES) cell lineage expressing enhanced green fluorescent protein (EGFP) under the control of a-myosin heavy chain (alpha-MHC) promoter (p alpha MHC-EGFP), we investigated the cardiomyogenic effects of 7 synthetic peptides (Betrofin3, FGLs, FGL(L), hNgf_C2, EnkaminE, Plannexin and C3) on cardiac differentiation. The expression of several cardiac-specific markers was determined by RT-PCR whereas the structural and functional properties of derived cardiomyocytes were examined by immunofluorescence and electrophysiology, respectively. Results: The results revealed that Betrofin3, an agonist of brain derived neurotrophic factor (BDNF) peptide exerted the most striking pro-cardiomyogenic effect on ES cells. We found that BDNF receptor, TrkB expression was up-regulated during differentiation. Treatment of differentiating cells with Betrofin3 between days 3 and 5 enhanced the expression of cardiac-specific markers and improved cardiomyocyte differentiation and functionality as revealed by genes regulation, flow cytometry and patch clamp analysis. Thus Betrofin3 may exert its cardiomyogenic effects on ES cells via TrkB receptor. Conclusion: Taken together, the results suggest that Betrofin3 modulates BDNF signaling with positive cardiomyogenic effect in stage and dose-dependent manner providing an effective strategy to increase ES cell-based generation of cardiomyocytes and offer a novel therapeutic approach to cardiac pathologies where BDNF levels are impaired. Introduction Copyright (C) 2015 S. Karger AG, Basel

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Xu, RuodanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Srinivasan, Sureshkumar PerumalUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sureshkumar, PoornimaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nembo, Erastus NembuUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schaefer, ChristophUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Semmler, JudithUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Matzkiesb, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Albrechtsena, MortenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hescheler, JuergenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nguemo, FilomainUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-416372
DOI: 10.1159/000374044
Journal or Publication Title: Cell. Physiol. Biochem.
Volume: 35
Number: 6
Page Range: S. 2437 - 2451
Date: 2015
Publisher: KARGER
Place of Publication: BASEL
ISSN: 1421-9778
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
N-CAM; HEART DEVELOPMENT; CARDIAC DIFFERENTIATION; NEUROTROPHIC FACTOR; NEURITE OUTGROWTH; PROGENITOR CELLS; BDNF; EXPRESSION; NCAM; PROLIFERATIONMultiple languages
Cell Biology; PhysiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/41637

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