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Nat Commun. 2016 Jan 19;7:10312. doi: 10.1038/ncomms10312.

Autonomous beating rate adaptation in human stem cell-derived cardiomyocytes.

Author information

1
Department of Biomedical Engineering, Columbia University, New York, New York 10027, USA.
2
College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
3
Department of Pharmacology, Columbia University, New York, New York 10032, USA.
4
McEwen Centre for Regenerative Medicine, University Health Network, Toronto, Ontario, Canada M5G1L7.
5
Department of Pathology and Cell Biology, Columbia University, New York, New York 10032, USA.
6
Department of Medicine, Columbia University, New York, New York 10032, USA.

Abstract

The therapeutic success of human stem cell-derived cardiomyocytes critically depends on their ability to respond to and integrate with the surrounding electromechanical environment. Currently, the immaturity of human cardiomyocytes derived from stem cells limits their utility for regenerative medicine and biological research. We hypothesize that biomimetic electrical signals regulate the intrinsic beating properties of cardiomyocytes. Here we show that electrical conditioning of human stem cell-derived cardiomyocytes in three-dimensional culture promotes cardiomyocyte maturation, alters their automaticity and enhances connexin expression. Cardiomyocytes adapt their autonomous beating rate to the frequency at which they were stimulated, an effect mediated by the emergence of a rapidly depolarizing cell population, and the expression of hERG. This rate-adaptive behaviour is long lasting and transferable to the surrounding cardiomyocytes. Thus, electrical conditioning may be used to promote cardiomyocyte maturation and establish their automaticity, with implications for cell-based reduction of arrhythmia during heart regeneration.

PMID:
26785135
PMCID:
PMC4735644
DOI:
10.1038/ncomms10312
[Indexed for MEDLINE]
Free PMC Article

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