Autonomous beating rate adaptation in human stem cell-derived cardiomyocytes

George Eng, Benjamin W. Lee, Lev Protas, Mark Gagliardi, Kristy Brown, Robert S. Kass, Gordon Keller, Richard B. Robinson and Gordana Vunjak-Novakovic ()
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George Eng: Columbia University
Benjamin W. Lee: Columbia University
Lev Protas: Columbia University
Mark Gagliardi: McEwen Centre for Regenerative Medicine, University Health Network
Kristy Brown: Columbia University
Robert S. Kass: Columbia University
Gordon Keller: McEwen Centre for Regenerative Medicine, University Health Network
Richard B. Robinson: Columbia University
Gordana Vunjak-Novakovic: Columbia University

Nature Communications, 2016, vol. 7, issue 1, 1-10

Abstract: 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.

Date: 2016
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10312

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DOI: 10.1038/ncomms10312

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