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Fischer, C.* ; Milting, H.* ; Fein, E.* ; Reiser, E.* ; Lu, K.* ; Seidel, T.* ; Schinner, C.* ; Schwarzmayr, T. ; Schramm, R.* ; Tomasi, R.* ; Husse, B.* ; Cao-Ehlker, X.* ; Pohl, U.* ; Dendorfer, A.*

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

Nat. Commun. 10:117 (2019)
Publ. Version/Full Text Research data DOI PMC
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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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Transverse Tubular System; Cardiac Tissue; Slices; Maturation; Strategies; Culture; Drug; Rat
Language
Publication Year 2019
HGF-reported in Year 2019
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Journal Nature Communications
Quellenangaben Volume: 10, Issue: 1, Pages: , Article Number: 117 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed
Institute(s) Institute of Human Genetics (IHG)
POF-Topic(s) 30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
Research field(s) Genetics and Epidemiology
PSP Element(s) G-500700-001
DOI 10.1038/s41467-018-08003-1
WOS ID WOS:000455354800014
Scopus ID 85059828102
PubMed ID 30631059
Erfassungsdatum 2019-03-11
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