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

Author

Listed:
  • 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
    Clinic of Cardiac Surgery, University Hospital, LMU Munich)

  • Roland Tomasi

    (University Hospital, LMU Munich
    Clinic of Anaesthesiology, University Hospital, LMU Munich)

  • Britta Husse

    (University Hospital, LMU Munich)

  • Xiaochun Cao-Ehlker

    (University Hospital, LMU Munich)

  • Ulrich Pohl

    (University Hospital, LMU Munich
    German Center for Cardiovascular Research, partner site Munich Heart Alliance)

  • Andreas Dendorfer

    (University Hospital, LMU Munich
    German Center for Cardiovascular Research, partner site Munich Heart Alliance)

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.

Suggested Citation

  • 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 &, 2019. "Long-term functional and structural preservation of precision-cut human myocardium under continuous electromechanical stimulation in vitro," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-018-08003-1
    DOI: 10.1038/s41467-018-08003-1
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    Cited by:

    1. Mariana Shumliakivska & Guillermo Luxán & Inga Hemmerling & Marina Scheller & Xue Li & Carsten Müller-Tidow & Bianca Schuhmacher & Zhengwu Sun & Andreas Dendorfer & Alisa Debes & Simone-Franziska Glas, 2024. "DNMT3A clonal hematopoiesis-driver mutations induce cardiac fibrosis by paracrine activation of fibroblasts," Nature Communications, Nature, vol. 15(1), pages 1-20, December.

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