Long-term functional and structural preservation of precision-cut human myocardium under continuous electromechanical stimulation in vitro

Carola Fischer, Hendrik Milting, Evelyn Fein, Elisabeth Reiser, Kun Lu, Thomas Seidel, Camilla Schinner, Thomas Schwarzmayr, Rene Schramm, Roland Tomasi, Britta Husse, Xiaochun Cao-Ehlker, Ulrich Pohl and Andreas Dendorfer ()
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Carola Fischer: University Hospital, LMU Munich
Hendrik Milting: Erich & Hanna Klessmann Institute, Clinic for Thoracic and Cardiovascular Surgery, Heart and Diabetes Center NRW, Ruhr-University Bochum
Evelyn Fein: University Hospital, LMU Munich
Elisabeth Reiser: University Hospital, LMU Munich
Kun Lu: University Hospital, LMU Munich
Thomas Seidel: Institute of Cellular and Molecular Physiology, Friedrich-Alexander University Erlangen-Nürnberg
Camilla Schinner: Institute of Anatomy, Ludwig-Maximilians-University Munich
Thomas Schwarzmayr: Institute of Human Genetics, Helmholtz Zentrum München
Rene Schramm: Erich & Hanna Klessmann Institute, Clinic for Thoracic and Cardiovascular Surgery, Heart and Diabetes Center NRW, Ruhr-University Bochum
Roland Tomasi: University Hospital, LMU Munich
Britta Husse: University Hospital, LMU Munich
Xiaochun Cao-Ehlker: University Hospital, LMU Munich
Ulrich Pohl: University Hospital, LMU Munich
Andreas Dendorfer: University Hospital, LMU Munich

Nature Communications, 2019, vol. 10, issue 1, 1-12

Abstract: Abstract In vitro models incorporating the complexity and function of adult human tissues are highly desired for translational research. Whilst vital slices of human myocardium approach these demands, their rapid degeneration in tissue culture precludes long-term experimentation. Here, we report preservation of structure and performance of human myocardium under conditions of physiological preload, compliance, and continuous excitation. In biomimetic culture, tissue slices prepared from explanted failing human hearts attain a stable state of contractility that can be monitored for up to 4 months or 2000000 beats in vitro. Cultured myocardium undergoes particular alterations in biomechanics, structure, and mRNA expression. The suitability of the model for drug safety evaluation is exemplified by repeated assessment of refractory period that permits sensitive analysis of repolarization impairment induced by the multimodal hERG-inhibitor pentamidine. Biomimetic tissue culture will provide new opportunities to study drug targets, gene functions, and cellular plasticity in adult human myocardium.

Date: 2019
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DOI: 10.1038/s41467-018-08003-1

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