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Development and evaluation of next-generation cardiotoxicity assay based on embryonic stem cell-derived cardiomyocytes
Cited 1 time in
Web of Science
Cited 2 time in Scopus
- Authors
- Issue Date
- 2020-08-31
- Publisher
- 생화학분자생물학회
- Citation
- BMB Reports, Vol.53 No.8, pp.437-441
- 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 doxolubicin, or 100 mg/kg nifedipine, while in vitro rat-CMs and hESC-CMs were treated with 5 mu M isoproterenol, 5 mu M doxolubicin, and 50 mu M 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.
- ISSN
- 1976-6696
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