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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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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)
  • Received : 2020.02.03
  • Accepted : 2020.02.28
  • Published : 2020.08.31
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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.

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References

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