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Stem Cell Reports. 2014 Apr 17;2(5):592-605. doi: 10.1016/j.stemcr.2014.03.006. eCollection 2014 May 6.

Programming and isolation of highly pure physiologically and pharmacologically functional sinus-nodal bodies from pluripotent stem cells.

Author information

1
Referenz und Translationszentrum für Kardiale Stammzelltherapie (RTC) der Universität Rostock, 18057 Rostock, Germany.
2
Universitätsklinik für Innere Medizin III, Kardiologie und Angiologie, 6020 Innsbruck, Austria ; Walter Brendel Centre, LMU Munich, 81377 Munich, Germany.
3
Gene Center Munich, LMU Munich, 81377 Munich, Germany.
4
Institut für Experimentelle und Klinische Pharmakologie und Toxikologie der FAU Erlangen-Nürnberg, 91054 Erlangen, Germany.
5
Walter Brendel Centre, LMU Munich, 81377 Munich, Germany ; German Center for Cardiovascular Research (DZHK), partner site Munich Heart Alliance, Munich, Germany.
6
Universitätsklinik für Innere Medizin III, Kardiologie und Angiologie, 6020 Innsbruck, Austria.

Abstract

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.

PMID:
24936448
PMCID:
PMC4050488
DOI:
10.1016/j.stemcr.2014.03.006
[Indexed for MEDLINE]
Free PMC Article

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