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Human Organotypic Cultured Cardiac Slices: New Platform For High Throughput Preclinical Human Trials

Kang, C, Qiao, Y, Li, G, Baechle, K, Camelliti, P, Rentschler, S and Efimov, IR (2016) Human Organotypic Cultured Cardiac Slices: New Platform For High Throughput Preclinical Human Trials Scientific Reports.

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Abstract

Translation of novel therapies from bench to bedside is hampered by profound disparities between animal and human genetics and physiology. The ability to test for efficacy and cardiotoxicity in a clinically relevant human model system would enable more rapid therapy development. We have developed a preclinical platform for validation of new therapies in human heart tissue using organotypic slices isolated from donor and endstage failing hearts. A major advantage of the slices when compared with human iPSderived cardiomyocytes is that native tissue architecture and extracellular matrix are preserved, thereby allowing investigation of multi-cellular physiology in normal or diseased myocardium. To validate this model, we used optical mapping of transmembrane potential and calcium transients. We found that normal human electrophysiology is preserved in slice preparations when compared with intact hearts, including slices obtained from the region of the sinus node. Physiology is maintained in slices during culture, enabling testing the acute and chronic effects of pharmacological, gene, cell, optogenetic, device, and other therapies. This methodology offers a powerful high-throughput platform for assessing the physiological response of the human heart to disease and novel putative therapies.

Item Type: Article
Subjects : Biosciences
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
AuthorsEmailORCID
Kang, CUNSPECIFIEDUNSPECIFIED
Qiao, YUNSPECIFIEDUNSPECIFIED
Li, GUNSPECIFIEDUNSPECIFIED
Baechle, KUNSPECIFIEDUNSPECIFIED
Camelliti, PUNSPECIFIEDUNSPECIFIED
Rentschler, SUNSPECIFIEDUNSPECIFIED
Efimov, IRUNSPECIFIEDUNSPECIFIED
Date : 2016
Copyright Disclaimer : This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Related URLs :
Depositing User : Symplectic Elements
Date Deposited : 16 Jun 2016 12:20
Last Modified : 16 Jun 2016 12:20
URI: http://epubs.surrey.ac.uk/id/eprint/811015

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