A practical guide for investigating cardiac physiology using living myocardial slices
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REVIEW
A practical guide for investigating cardiac physiology using living myocardial slices S. A. Watson3 · A. Dendorfer4 · T. Thum1,2 · F. Perbellini1 Received: 8 July 2020 / Accepted: 10 August 2020 © The Author(s) 2020
Abstract Ex vivo multicellular preparations are essential tools to study tissue physiology. Among them, the recent methodological and technological developments in living myocardial slices (LMS) are attracting increasing interest by the cardiac research field. Despite this, this research model remains poorly perceived and utilized by most research laboratories. Here, we provide a practical guide on how to use LMS to interrogate multiple aspects of cardiac function, structure and biochemistry. We discuss issues that should be considered to conduct successful experiments, including experimental design, sample preparation, data collection and analysis. We describe how laboratory setups can be adapted to accommodate and interrogate this multicellular research model. These adaptations can often be achieved at a reasonable cost with off-the-shelf components and operated reliably using well-established protocols and freely available software, which is essential to broaden the utilization of this method. We will also highlight how current measurements can be improved to further enhance data quality and reliability to ensure inter-laboratory reproducibility. Finally, we summarize the most promising biomedical applications and envision how living myocardial slices can lead to further breakthroughs. Keywords Cardiovascular models · Multicellularity · Living myocardial slice · Translational research
Introduction: why use living myocardial slices? Our collective understanding of the cellular processes involved in cardiac physiology and remodeling is primarily derived from isolated cells, where complex tissue architecture, extracellular matrix, native multicellularity and intercellular communication are lost. While the simplicity of these platforms is attractive, the data obtained are somewhat ‘oversimplified’ and cells cultured in vitro tend to display * T. Thum Thum.Thomas@mh‑hannover.de * F. Perbellini Perbellini.Filippo@mh‑hannover.de 1
Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Hanover, Germany
2
National Heart and Lung Institute, Imperial College London, London, UK
3
King’s College Hospital, London, UK
4
Walter‑Brendel‑Centre of Experimental Medicine, University Hospital, LMU Munich, Munich, Germany
aberrant behaviors and altered phenotype [2, 11]. Knowledge has also been derived from whole heart and isolated muscle (papillary and trabeculae) studies, which both retain maximal proximity to the in vivo environment. However, these models lack significant throughput and their use for chronic in vitro studies is limited [38, 45]. What is needed are novel multicellular models, capable of better simulating the physiological milieu, that bridge the gap between conventional cultures and complex in vivo preparations, while facilita
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