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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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

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Cytochrome P-450 CYP3A
Bioreactors
Hepatocytes
Pharmaceutical Preparations
Microvilli
Testosterone
Albumins
Liver
Proteins

ASJC Scopus subject areas

  • Genetics

Cite this

Expression of CYP3A4 by an immortalized human hepatocyte line in a three-dimensional culture using a radial-flow bioreactor. / Akiyama, Ichiro; Tomiyama, Koji; Sakaguchi, Masakiyo; Takaishi, Mikiro; Mori, Masaharu; Hosokawa, Masakiyo; Nagamori, Seishi; Shimizu, Nobuyoshi; Huh, Nam Ho; Miyazaki, Masahiro.

In: International Journal of Molecular Medicine, Vol. 14, No. 4, 10.2004, p. 663-668.

Research output: Contribution to journalArticle

Akiyama, I, Tomiyama, K, Sakaguchi, M, Takaishi, M, Mori, M, Hosokawa, M, Nagamori, S, Shimizu, N, Huh, NH & 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, vol. 14, no. 4, pp. 663-668.
Akiyama, Ichiro ; Tomiyama, Koji ; Sakaguchi, Masakiyo ; Takaishi, Mikiro ; Mori, Masaharu ; Hosokawa, Masakiyo ; Nagamori, Seishi ; Shimizu, Nobuyoshi ; Huh, Nam Ho ; Miyazaki, Masahiro. / Expression of CYP3A4 by an immortalized human hepatocyte line in a three-dimensional culture using a radial-flow bioreactor. In: International Journal of Molecular Medicine. 2004 ; Vol. 14, No. 4. pp. 663-668.
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