Programming and Isolation of Highly Pure Physiologically and Pharmacologically Functional Sinus-Nodal Bodies from Pluripotent Stem Cells
Therapeutic approaches for “sick sinus syndrome” rely on electrical pacemakers, which lack hormone responsiveness and bear hazards such as infection and battery failure. These issues may be overcome via “biological pacemakers” derived from pluripotent stem cells (PSCs). Here, we show that forward pr...
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doaj-eb164d8eddd342b28bb5a824538203dd2020-11-24T21:23:57ZengElsevierStem Cell Reports2213-67112014-05-012559260510.1016/j.stemcr.2014.03.006Programming and Isolation of Highly Pure Physiologically and Pharmacologically Functional Sinus-Nodal Bodies from Pluripotent Stem CellsJulia Jeannine Jung0Britta Husse1Christian Rimmbach2Stefan Krebs3Juliane Stieber4Gustav Steinhoff5Andreas Dendorfer6Wolfgang-Michael Franz7Robert David8Referenz und Translationszentrum für Kardiale Stammzelltherapie (RTC) der Universität Rostock, 18057 Rostock, GermanyUniversitätsklinik für Innere Medizin III, Kardiologie und Angiologie, 6020 Innsbruck, AustriaReferenz und Translationszentrum für Kardiale Stammzelltherapie (RTC) der Universität Rostock, 18057 Rostock, GermanyGene Center Munich, LMU Munich, 81377 Munich, GermanyInstitut für Experimentelle und Klinische Pharmakologie und Toxikologie der FAU Erlangen-Nürnberg, 91054 Erlangen, GermanyReferenz und Translationszentrum für Kardiale Stammzelltherapie (RTC) der Universität Rostock, 18057 Rostock, GermanyWalter Brendel Centre, LMU Munich, 81377 Munich, GermanyUniversitätsklinik für Innere Medizin III, Kardiologie und Angiologie, 6020 Innsbruck, AustriaReferenz und Translationszentrum für Kardiale Stammzelltherapie (RTC) der Universität Rostock, 18057 Rostock, GermanyTherapeutic approaches for “sick sinus syndrome” rely on electrical pacemakers, which lack hormone responsiveness and bear hazards such as infection and battery failure. These issues may be overcome via “biological pacemakers” derived from pluripotent stem cells (PSCs). Here, we show that forward programming of PSCs with the nodal cell inducer TBX3 plus an additional Myh6-promoter-based antibiotic selection leads to cardiomyocyte aggregates consisting of >80% physiologically and pharmacologically functional pacemaker cells. These induced sinoatrial bodies (iSABs) exhibited highly increased beating rates (300–400 bpm), coming close to those found in mouse hearts, and were able to robustly pace myocardium ex vivo. Our study introduces iSABs as highly pure, functional nodal tissue that is derived from PSCs and may be important for future cell therapies and drug testing in vitro.http://www.sciencedirect.com/science/article/pii/S221367111400085X |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Julia Jeannine Jung Britta Husse Christian Rimmbach Stefan Krebs Juliane Stieber Gustav Steinhoff Andreas Dendorfer Wolfgang-Michael Franz Robert David |
spellingShingle |
Julia Jeannine Jung Britta Husse Christian Rimmbach Stefan Krebs Juliane Stieber Gustav Steinhoff Andreas Dendorfer Wolfgang-Michael Franz Robert David Programming and Isolation of Highly Pure Physiologically and Pharmacologically Functional Sinus-Nodal Bodies from Pluripotent Stem Cells Stem Cell Reports |
author_facet |
Julia Jeannine Jung Britta Husse Christian Rimmbach Stefan Krebs Juliane Stieber Gustav Steinhoff Andreas Dendorfer Wolfgang-Michael Franz Robert David |
author_sort |
Julia Jeannine Jung |
title |
Programming and Isolation of Highly Pure Physiologically and Pharmacologically Functional Sinus-Nodal Bodies from Pluripotent Stem Cells |
title_short |
Programming and Isolation of Highly Pure Physiologically and Pharmacologically Functional Sinus-Nodal Bodies from Pluripotent Stem Cells |
title_full |
Programming and Isolation of Highly Pure Physiologically and Pharmacologically Functional Sinus-Nodal Bodies from Pluripotent Stem Cells |
title_fullStr |
Programming and Isolation of Highly Pure Physiologically and Pharmacologically Functional Sinus-Nodal Bodies from Pluripotent Stem Cells |
title_full_unstemmed |
Programming and Isolation of Highly Pure Physiologically and Pharmacologically Functional Sinus-Nodal Bodies from Pluripotent Stem Cells |
title_sort |
programming and isolation of highly pure physiologically and pharmacologically functional sinus-nodal bodies from pluripotent stem cells |
publisher |
Elsevier |
series |
Stem Cell Reports |
issn |
2213-6711 |
publishDate |
2014-05-01 |
description |
Therapeutic approaches for “sick sinus syndrome” rely on electrical pacemakers, which lack hormone responsiveness and bear hazards such as infection and battery failure. These issues may be overcome via “biological pacemakers” derived from pluripotent stem cells (PSCs). Here, we show that forward programming of PSCs with the nodal cell inducer TBX3 plus an additional Myh6-promoter-based antibiotic selection leads to cardiomyocyte aggregates consisting of >80% physiologically and pharmacologically functional pacemaker cells. These induced sinoatrial bodies (iSABs) exhibited highly increased beating rates (300–400 bpm), coming close to those found in mouse hearts, and were able to robustly pace myocardium ex vivo. Our study introduces iSABs as highly pure, functional nodal tissue that is derived from PSCs and may be important for future cell therapies and drug testing in vitro. |
url |
http://www.sciencedirect.com/science/article/pii/S221367111400085X |
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