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KMID : 0624620200530080437
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BMB Reports
2020 Volume.53 No. 8 p.437 ~ p.441
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Development and evaluation of next-generation cardiotoxicity assay based on embryonic stem cell-derived cardiomyocytes
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Ryu Bo-Kyeong
Choi Seong-Woo
Lee Seul-Gi
Jeong Young-Hoon
Kim Uk-Jin
Kim Jin
Jung Cho-Rok
Chung Hyung-Min
Park Jae-Hak
Kim C-Yoon
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Abstract
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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.
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KEYWORD
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Alternative, Cardiomyocyte, Drug withdrawal, Embryonic stem cell, Toxicity test
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