Iglesias-Garcia, Olalla, Baumgartner, Sven, Macri-Pellizzeri, Laura, Roberto Rodriguez-Madoz, Juan, Abizanda, Gloria ORCID: 0000-0002-2504-5163, Guruceaga, Elizabeth ORCID: 0000-0003-0547-681X, Albiasu, Edurne, Corbacho, David, Benavides-Vallve, Carolina, Soriano-Navarro, Mario, Gonzalez-Granero, Susana, Jose Gavira, Juan, Krausgrill, Benjamin, Rodriguez-Manero, Moises ORCID: 0000-0001-7566-9321, Manuel Garcia-Verdugo, Jose, Ortiz-de-Solorzano, Carlos, Halbach, Marcel, Hescheler, Juergen, Pelacho, Beatriz and Prosper, Felipe ORCID: 0000-0001-6115-8790 (2015). Neuregulin-1 beta Induces Mature Ventricular Cardiac Differentiation from Induced Pluripotent Stem Cells Contributing to Cardiac Tissue Repair. Stem Cells Dev., 24 (4). S. 484 - 497. NEW ROCHELLE: MARY ANN LIEBERT, INC. ISSN 1557-8534

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Abstract

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-1 beta (NRG-1 beta) treatment could enhance in vitro generation of mature working-type CMs from induced pluripotent stem (iPS) cells and assess the regenerative effects of these CMs on cardiac tissue after acute myocardial infarction (AMI). With that purpose, adult mouse fibroblast-derived iPS from alpha-MHC-GFP mice were derived and differentiated into CMs through NRG-1 beta and/or dimethyl sulfoxide (DMSO) treatment. Cardiac specification and maturation of the iPS was analyzed by gene expression array, quantitative real-time polymerase chain reaction, 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 after coronary artery ligation, and functional and histology changes were assessed from 1 to 8 weeks post-transplantation. On 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-1 beta and DMSO compared with 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 adequate heart tissue remodeling. In conclusion, we have demonstrated that combined treatment with NRG-1 beta and DMSO leads to efficient differentiation of iPS into ventricular-like cardiac cells with a higher degree of maturation, which are capable of preserving cardiac function and tissue viability when transplanted into a mouse model of AMI.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Iglesias-Garcia, OlallaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Baumgartner, SvenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Macri-Pellizzeri, LauraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Roberto Rodriguez-Madoz, JuanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Abizanda, GloriaUNSPECIFIEDorcid.org/0000-0002-2504-5163UNSPECIFIED
Guruceaga, ElizabethUNSPECIFIEDorcid.org/0000-0003-0547-681XUNSPECIFIED
Albiasu, EdurneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Corbacho, DavidUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Benavides-Vallve, CarolinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Soriano-Navarro, MarioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gonzalez-Granero, SusanaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jose Gavira, JuanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Krausgrill, BenjaminUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rodriguez-Manero, MoisesUNSPECIFIEDorcid.org/0000-0001-7566-9321UNSPECIFIED
Manuel Garcia-Verdugo, JoseUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ortiz-de-Solorzano, CarlosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Halbach, MarcelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hescheler, JuergenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pelacho, BeatrizUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Prosper, FelipeUNSPECIFIEDorcid.org/0000-0001-6115-8790UNSPECIFIED
URN: urn:nbn:de:hbz:38-412487
DOI: 10.1089/scd.2014.0211
Journal or Publication Title: Stem Cells Dev.
Volume: 24
Number: 4
Page Range: S. 484 - 497
Date: 2015
Publisher: MARY ANN LIEBERT, INC
Place of Publication: NEW ROCHELLE
ISSN: 1557-8534
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
LIGHT-CHAIN KINASE; MYOCARDIAL-INFARCTION; FETAL CARDIOMYOCYTES; SURVIVAL; INTEGRATION; TRANSPLANTATION; ACTIVATION; PROMOTES; MYOCYTES; GROWTHMultiple languages
Cell & Tissue Engineering; Hematology; Medicine, Research & Experimental; TransplantationMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/41248

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