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http://dx.doi.org/10.5483/BMBRep.2020.53.8.022

Development and evaluation of next-generation cardiotoxicity assay based on embryonic stem cell-derived cardiomyocytes  

Ryu, Bokyeong (Department of Laboratory Animal Medicine, College of Veterinary Medicine, Seoul National University)
Choi, Seong Woo (Department of Medicine, School of Medicine, Konkuk University)
Lee, Seul-Gi (Department of Medicine, School of Medicine, Konkuk University)
Jeong, Young-Hoon (Department of Medicine, School of Medicine, Konkuk University)
Kim, Ukjin (Department of Laboratory Animal Medicine, College of Veterinary Medicine, Seoul National University)
Kim, Jin (Department of Laboratory Animal Medicine, College of Veterinary Medicine, Seoul National University)
Jung, Cho-Rok (Gene Therapy Research Unit, Korea Research Institute of Bioscience and Biotechnology)
Chung, Hyung-Min (Department of Medicine, School of Medicine, Konkuk University)
Park, Jae-Hak (Department of Laboratory Animal Medicine, College of Veterinary Medicine, Seoul National University)
Kim, C-Yoon (Department of Medicine, School of Medicine, Konkuk University)
Publication Information
BMB Reports / v.53, no.8, 2020 , pp. 437-441 More about this Journal
Abstract
In accordance with requirements of the ICH S7B safety pharmacology guidelines, numerous next-generation cardiotoxicity studies using human stem cell-derived cardiomyocytes (CMs) are being conducted globally. Although several stem cell-derived CMs are being developed for commercialization, there is insufficient research to verify if these CMs can replace animal experiments. In this study, in vitro high-efficiency CMs derived from human embryonic stem cells (hESC-CMs) were compared with Sprague-Dawley rats as in vivo experimental animals, and primary cultured in vitro rat-CMs for cardiotoxicity tests. In vivo rats were administrated with two consecutive injections of 100 mg/kg isoproterenol, 15 mg/kg doxorubicin, or 100 mg/kg nifedipine, while in vitro rat-CMs and hESC-CMs were treated with 5 μM isoproterenol, 5 μM doxorubicin, and 50 μM nifedipine. We have verified the equivalence of hESC-CMs assessments over various molecular biological markers, morphological analysis. Also, we have identified the advantages of hESC-CMs, which can distinguish between species variability, over electrophysiological analysis of ion channels against cardiac damage. Our findings demonstrate the possibility and advantage of high-efficiency hESC-CMs as next-generation cardiotoxicity assessment.
Keywords
Alternative; Cardiomyocyte; Drug withdrawal; Embryonic stem cell; Toxicity test;
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