Document Detail


NRG-1b Induces Mature Ventricular Cardiac Differentiation from Induced Pluripotent Stem Cells Contributing to Cardiac Tissue Repair.
MedLine Citation:
PMID:  25329043     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Stem cell-derived cardiomyocytes (CMs) are often electrophysiologically immature and heterogeneous, which represents a major barrier to their in vitro and in vivo application. Therefore, the purpose of this study was to examine whether Neuregulin-1b (NRG-1b) treatment could enhance in vitro generation of mature "working-type" CMs from induced pluripotent stem cells (iPS) and assessed the regenerative effects of these CMs on cardiac tissue following acute myocardial infarction (AMI). With that purpose, adult mouse fibroblast-derived iPS from α-MHC-GFP mice were derived and differentiated into CMs through NRG-1b and/or DMSO treatment. Cardiac specification and maturation of the iPS was analyzed by gene expression array, qRT-PCR, immunofluorescence, electron microscopy, and patch-clamp techniques. In vivo, the iPS-derived CMs or culture medium-control were injected into the peri-infarct region of hearts following coronary artery ligation, and functional and histology changes assessed from 1-8 weeks post-transplantation. Upon differentiation, the iPS displayed early and robust in vitro cardiogenesis, expressing cardiac-specific genes and proteins. More importantly, electrophysiological studies demonstrated that a more mature ventricular-like cardiac phenotype was achieved when cells were treated with NRG-1b and DMSO compared to DMSO alone. Furthermore, in vivo studies demonstrated that iPS-derived CMs were able to engraft and electromechanically couple to heart tissue, ultimately preserving cardiac function and inducing and adequate heart tissue remodeling. In conclusion, we have demonstrated that combined treatment with NRG-1b and DMSO leads to efficient differentiation of iPS into mature ventricular-like cardiac cells, which are capable of preserving cardiac function and tissue viability when transplanted into a mouse model of AMI.
Authors:
Olalla Iglesias-Garcia; Sven Baumgartner; Laura Macri-Pellizzeri; Juan R Rodriguez; Gloria Abizanda; Elizabeth Guruceaga; Edurne Albiasu; David Corbacho; Carolina Benavides-Vallve; Mario Soriano-Navarro; Susana Gonzalez-Granero; Juan J Gavira; Benjamin Krausgrill; Moises Rodriguez-Mañero; Jose Manuel Garcia-Verdugo; Carlos Ortiz-de-Solorzano; Marcel Halbach; Juergen Hescheler; Beatriz Pelacho; Felipe Prósper
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-10-20
Journal Detail:
Title:  Stem cells and development     Volume:  -     ISSN:  1557-8534     ISO Abbreviation:  Stem Cells Dev.     Publication Date:  2014 Oct 
Date Detail:
Created Date:  2014-10-20     Completed Date:  -     Revised Date:  2014-10-21    
Medline Journal Info:
Nlm Unique ID:  101197107     Medline TA:  Stem Cells Dev     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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