Prediction of hepatotoxicity for drugs using human pluripotent stem cell-derived hepatocytes

Jong Hyun Kim, Min Wang, Jaehun Lee, Han Jin Park, Chungseong Han, Hee Su Hong, Jeong Seong Kim, Geun Ho An, Kijung Park, Hee Kyung Park, Shi Feng Zhu, Xiao Bo Sun, Jong-Hoon Kim, Dong Hun Woo

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12 Citations (Scopus)

Abstract

Drug-induced liver toxicity is a main reason for withdrawals of new drugs in late clinical phases and post-launch of the drugs. Thus, hepatotoxicity screening of drug candidates in pre-clinical stage is important for reducing drug attrition rates during the clinical development process. Here, we show commercially available hepatocytes that could be used for early toxicity evaluation of drug candidates. From our hepatic differentiation technology, we obtained highly pure (≥98%) hepatocytes from human embryonic stem cells (hESCs) having mature phenotypes and similar gene expression profiles with those of primary human tissues. Furthermore, we optimized 96-well culture condition of hESC-derived hepatocytes suitable for toxicity tests in vitro. To this end, we demonstrated the efficacy of our optimized hepatocyte model for predicting hepatotoxicity against the Chinese herbal medicines and showed that toxicity patterns from our hepatocyte model was similar to those of human primary cultured hepatocytes. We conclude that toxicity test using our hepatocyte model could be a good alternative cell source for pre-clinical study to predict potential hepatotoxicity in drug discovery industries.

Original languageEnglish
Pages (from-to)1-14
Number of pages14
JournalCell Biology and Toxicology
DOIs
Publication statusAccepted/In press - 2017 Apr 5

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Keywords

  • Drug screening
  • Hepatocytes
  • Human embryonic stem cells
  • Toxicity test

ASJC Scopus subject areas

  • Toxicology
  • Cell Biology
  • Health, Toxicology and Mutagenesis

Cite this

Kim, J. H., Wang, M., Lee, J., Park, H. J., Han, C., Hong, H. S., Kim, J. S., An, G. H., Park, K., Park, H. K., Zhu, S. F., Sun, X. B., Kim, J-H., & Woo, D. H. (Accepted/In press). Prediction of hepatotoxicity for drugs using human pluripotent stem cell-derived hepatocytes. Cell Biology and Toxicology, 1-14. https://doi.org/10.1007/s10565-017-9392-y