Expression of CYP3A4 by an immortalized human hepatocyte line in a three-dimensional culture using a radial-flow bioreactor.

Ichiro Akiyama, Koji Tomiyama, Masakiyo Sakaguchi, Mikiro Takaishi, Masaharu Mori, Masakiyo Hosokawa, Seishi Nagamori, Nobuyoshi Shimizu, Nam Ho Huh, Masahiro Miyazaki

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15 Citations (Scopus)

Abstract

Cytochrome P450 (CYP) 3A is responsible for about 50% of drug metabolizing activity in the liver. The present study was undertaken to establish a CYP3A4-active model for in vitro analysis of human drug metabolism. The cells used were immortalized normal human fetal hepatocytes (OUMS-29) and its HNF4alpha-introduced subline (OUMS-29/H-11). The cells were cultivated under high-density three-dimensional conditions in a radial-flow bioreactor (RFB). The number of OUMS-29 cells increased 15-fold over 49 days and their apical surfaces were covered with abundant microvilli, a characteristic of hepatocytes in vivo. The amount of albumin secreted by OUMS-29 cells in the three-dimensional RFB culture was 6-fold higher than those in a monolayer culture. CYP3A4 protein and an intermediate metabolite of testosterone by CYP3A4 were detected in OUMS-29/H11 cells cultivated in RFB >29 days. These results indicate that the RFB culture of OUMS-29/H-11 cells is useful for screening and developing new drugs.

Original languageEnglish
Pages (from-to)663-668
Number of pages6
JournalInternational journal of molecular medicine
Volume14
Issue number4
Publication statusPublished - Oct 2004

ASJC Scopus subject areas

  • Genetics

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    Akiyama, I., Tomiyama, K., Sakaguchi, M., Takaishi, M., Mori, M., Hosokawa, M., Nagamori, S., Shimizu, N., Huh, N. H., & Miyazaki, M. (2004). Expression of CYP3A4 by an immortalized human hepatocyte line in a three-dimensional culture using a radial-flow bioreactor. International journal of molecular medicine, 14(4), 663-668.