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Biomimetic electromechanical stimulation to maintain adult myocardial slices in vitro

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Title: Biomimetic electromechanical stimulation to maintain adult myocardial slices in vitro
Authors: Watson, S
Duff, J
Bardi, I
Zabielska, M
Atanur, S
Jabbour, R
Simon, A
Tomas, A
Smolenski, R
Harding, S
Terracciano, C
Item Type: Journal Article
Abstract: Adult cardiac tissue undergoes a rapid process of dedifferentiation when cultured outside the body. The in vivo environment, particularly constant electromechanical stimulation, is fundamental to the regulation of cardiac structure and function. We investigated the role of electromechanical stimulation in preventing culture-induced dedifferentiation of adult cardiac tissue using rat, rabbit and human heart failure myocardial slices. Here we report that the application of a preload equivalent to sarcomere length (SL) = 2.2 μm is optimal for the maintenance of rat myocardial slice structural, functional and transcriptional properties at 24 h. Gene sets associated with the preservation of structure and function are activated, while gene sets involved in dedifferentiation are suppressed. The maximum contractility of human heart failure myocardial slices at 24 h is also optimally maintained at SL = 2.2 μm. Rabbit myocardial slices cultured at SL = 2.2 μm remain stable for 5 days. This approach substantially prolongs the culture of adult cardiac tissue in vitro.
Issue Date: 15-May-2019
Date of Acceptance: 24-Apr-2019
URI: http://hdl.handle.net/10044/1/70295
DOI: https://dx.doi.org/10.1038/s41467-019-10175-3
ISSN: 2041-1723
Publisher: Nature Research (part of Springer Nature)
Journal / Book Title: Nature Communications
Volume: 10
Copyright Statement: © 2019 The Author(s). This article is licensed under a Creative CommonsAttribution 4.0 International License, which permits use, sharing,adaptation, distribution and reproduction in any medium or format, as long as you giveappropriate credit to the original author(s) and the source, provide a link to the CreativeCommons license, and indicate if changes were made. The images or other third partymaterial in this article are included in the article’s Creative Commons license, unlessindicated otherwise in a credit line to the material. If material is not included in thearticle’s Creative Commons license and your intended use is not permitted by statutoryregulation or exceeds the permitted use, you will need to obtain permission directly fromthe copyright holder. To view a copy of this license, visithttp://creativecommons.org/licenses/by/4.0/
Sponsor/Funder: British Heart Foundation
British Heart Foundation
British Heart Foundation
British Heart Foundation
British Heart Foundation
Medical Research Council (MRC)
Funder's Grant Number: FS/15/35/31529
FS/16/17/31663
WHCF_P66590
RM/17/1/33377
RE/18/4/34215
MR/R010676/1
Keywords: Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
CARDIAC MYOCYTES
TISSUE-SLICES
CELL
RAT
CARDIOMYOCYTES
ISOPROTERENOL
HYPERTROPHY
MATURATION
SKELETAL
THERAPY
MD Multidisciplinary
Publication Status: Published
Article Number: ARTN 2168
Appears in Collections:National Heart and Lung Institute
Department of Medicine
Faculty of Medicine



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