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Cardiomyocyte electrical-mechanical synchronized model for high-content, dose-quantitative and time-dependent drug assessment

Cardiovascular diseases have emerged as a significant threat to human health. However, drug development is a time-consuming and costly process, and few drugs pass the preclinical assessment of safety and efficacy. The existing patch-clamp, Ca(2+) imaging, and microelectrode array technologies in car...

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Autores principales: Fang, Jiaru, Wei, Xinwei, Li, Hongbo, Hu, Ning, Liu, Xingxing, Xu, Dongxin, Zhang, Tao, Wan, Hao, Wang, Ping, Xie, Xi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8433219/
https://www.ncbi.nlm.nih.gov/pubmed/34567740
http://dx.doi.org/10.1038/s41378-021-00247-0
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author Fang, Jiaru
Wei, Xinwei
Li, Hongbo
Hu, Ning
Liu, Xingxing
Xu, Dongxin
Zhang, Tao
Wan, Hao
Wang, Ping
Xie, Xi
author_facet Fang, Jiaru
Wei, Xinwei
Li, Hongbo
Hu, Ning
Liu, Xingxing
Xu, Dongxin
Zhang, Tao
Wan, Hao
Wang, Ping
Xie, Xi
author_sort Fang, Jiaru
collection PubMed
description Cardiovascular diseases have emerged as a significant threat to human health. However, drug development is a time-consuming and costly process, and few drugs pass the preclinical assessment of safety and efficacy. The existing patch-clamp, Ca(2+) imaging, and microelectrode array technologies in cardiomyocyte models for drug preclinical screening have suffered from issues of low throughput, limited long-term assessment, or inability to synchronously and correlatively analyze electrical and mechanical signals. Here, we develop a high-content, dose-quantitative and time-dependent drug assessment platform based on an electrical-mechanical synchronized (EMS) biosensing system. This microfabricated EMS can record both firing potential (FP) and mechanical beating (MB) signals from cardiomyocytes and extract a variety of characteristic parameters from these two signals (FP–MB) for further analysis. This system was applied to test typical ion channel drugs (lidocaine and isradipine), and the dynamic responses of cardiomyocytes to the tested drugs were recorded and analyzed. The high-throughput characteristics of the system can facilitate simultaneous experiments on a large number of samples. Furthermore, a database of various cardiac drugs can be established by heat map analysis for rapid and effective screening of drugs. The EMS biosensing system is highly promising as a powerful tool for the preclinical development of new medicines.
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spelling pubmed-84332192021-09-24 Cardiomyocyte electrical-mechanical synchronized model for high-content, dose-quantitative and time-dependent drug assessment Fang, Jiaru Wei, Xinwei Li, Hongbo Hu, Ning Liu, Xingxing Xu, Dongxin Zhang, Tao Wan, Hao Wang, Ping Xie, Xi Microsyst Nanoeng Article Cardiovascular diseases have emerged as a significant threat to human health. However, drug development is a time-consuming and costly process, and few drugs pass the preclinical assessment of safety and efficacy. The existing patch-clamp, Ca(2+) imaging, and microelectrode array technologies in cardiomyocyte models for drug preclinical screening have suffered from issues of low throughput, limited long-term assessment, or inability to synchronously and correlatively analyze electrical and mechanical signals. Here, we develop a high-content, dose-quantitative and time-dependent drug assessment platform based on an electrical-mechanical synchronized (EMS) biosensing system. This microfabricated EMS can record both firing potential (FP) and mechanical beating (MB) signals from cardiomyocytes and extract a variety of characteristic parameters from these two signals (FP–MB) for further analysis. This system was applied to test typical ion channel drugs (lidocaine and isradipine), and the dynamic responses of cardiomyocytes to the tested drugs were recorded and analyzed. The high-throughput characteristics of the system can facilitate simultaneous experiments on a large number of samples. Furthermore, a database of various cardiac drugs can be established by heat map analysis for rapid and effective screening of drugs. The EMS biosensing system is highly promising as a powerful tool for the preclinical development of new medicines. Nature Publishing Group UK 2021-03-25 /pmc/articles/PMC8433219/ /pubmed/34567740 http://dx.doi.org/10.1038/s41378-021-00247-0 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Fang, Jiaru
Wei, Xinwei
Li, Hongbo
Hu, Ning
Liu, Xingxing
Xu, Dongxin
Zhang, Tao
Wan, Hao
Wang, Ping
Xie, Xi
Cardiomyocyte electrical-mechanical synchronized model for high-content, dose-quantitative and time-dependent drug assessment
title Cardiomyocyte electrical-mechanical synchronized model for high-content, dose-quantitative and time-dependent drug assessment
title_full Cardiomyocyte electrical-mechanical synchronized model for high-content, dose-quantitative and time-dependent drug assessment
title_fullStr Cardiomyocyte electrical-mechanical synchronized model for high-content, dose-quantitative and time-dependent drug assessment
title_full_unstemmed Cardiomyocyte electrical-mechanical synchronized model for high-content, dose-quantitative and time-dependent drug assessment
title_short Cardiomyocyte electrical-mechanical synchronized model for high-content, dose-quantitative and time-dependent drug assessment
title_sort cardiomyocyte electrical-mechanical synchronized model for high-content, dose-quantitative and time-dependent drug assessment
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8433219/
https://www.ncbi.nlm.nih.gov/pubmed/34567740
http://dx.doi.org/10.1038/s41378-021-00247-0
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