PT - JOURNAL ARTICLE AU - Kenta Ite AU - Masashi Toyoda AU - Saeko Yoshioka AU - Takaaki Yukitake AU - Mayu Yamazaki-Inoue AU - Kuniko Tatsumi AU - Hidenori Akutsu AU - Hiroshi Nishina AU - Tohru Kimura AU - Naoko Ohtani AU - Atsuko Nakazawa AU - Mureo Kasahara AU - Akihiro Umezawa TI - Hepatocytes with a phenotype of substantial CYP3A4 induction generated from drug-associated fulminant hepatitis-derived induced pluripotent stem cells AID - 10.1101/2021.11.30.470519 DP - 2021 Jan 01 TA - bioRxiv PG - 2021.11.30.470519 4099 - http://biorxiv.org/content/early/2021/11/30/2021.11.30.470519.short 4100 - http://biorxiv.org/content/early/2021/11/30/2021.11.30.470519.full AB - Many drugs have the potential to induce the expression of drug-metabolizing enzymes, particularly cytochrome P450 3A4 (CYP3A4). Hepatocytes are often employed to evaluate drug-mediated CYP3A4 induction, but the variation between different cell lots is an issue that needs to be solved. Only a limited number of immortalized hepatocyte cell lines have been reported to date. In this study, we describe the successful generation of hepatocytes from disease-specific induced pluripotent stem cells (iPSCs) derived from a patient with fulminant hepatitis (FH-iPSCs). To examine the CYP3A4 induction potential, FH-iPSCs were induced into hepatocytes. Drug-mediated induction testing revealed that HepaKI exhibited a 57.2-fold increase in CYP3A4 after exposure to rifampicin, relative to control cells. These results suggest that FH-iPSCs are a preferred cell source for in vitro CYP3A4 induction assays.Competing Interest StatementAU designed experiments. KI, MT, SY, and TY performed experiments. KI and AU analyzed data. KI, MYI, KT, AN, and MK contributed reagents, materials and analysis tools. MT, HA, HN, TK, and NO discussed the data and manuscript. AU and KI wrote this manuscript.