Further investigation of 3D culture spheroid models of human hepatocytes

DOI Web Site Web Site PubMed 41 References
  • Ogihara Takuo
    Laboratory of Biopharmaceutics, Department of Pharmacology, Faculty of Pharmacy, Takasaki University of Health and Welfare
  • Hosono Mayu
    Laboratory of Biopharmaceutics, Department of Pharmacology, Faculty of Pharmacy, Takasaki University of Health and Welfare
  • Kojima Hajime
    Division of Risk Assessment, Biological Safety Research Center, National Institute of Health Sciences

Bibliographic Information

Other Title
  • ヒト肝細胞の3次元培養スフェロイドモデルの新展開
  • 創薬シリーズ(8)創薬研究の新潮流(31)ヒト肝細胞の3次元培養スフェロイドモデルの新展開
  • ソウヤク シリーズ(8)ソウヤク ケンキュウ ノ シン チョウリュウ(31)ヒト カン サイボウ ノ 3ジゲン バイヨウ スフェロイドモデル ノ シン テンカイ

Search this article

Abstract

<p>Three-dimensional (3D) cultured hepatocyte capable of maintaining liver-specific function in an in vivo state over a relatively long period of time have drawn attention as a new method for evaluating the metabolic process, hepatotoxicity and enzyme induction potential of drugs. When human hepatocytes were seeded on a plate for spheroid formation, and cell morphology and albumin secretion were examined, hepatocyte spheroid was stably maintained for at least 21 days after seeding. As a result of drug exposure to this spheroid, sequential metabolic reactions by Phase I and Phase II enzymes and metabolic reactions peculiar to only humans were observed. Moreover, when several drugs were exposed to spheroids and hepatotoxicity was evaluated, stable values were obtained for the 50% inhibitory concentration (IC50) of albumin secretion at 14 and 21 days. The IC50 values of most of the tested drugs were lower than in conventional assays, suggesting that the reported evaluation methods might underestimate hepatotoxicity. Furthermore, examination of mRNA expression level and activity of various cytochrome P450 (CYP) after exposure of typical inducers of CYPs to hepatocyte spheroid resulted in a significant increase in the expression level and activity of each. From these results, it was shown that this 3D hepatocyte spheroid system is suitable for follow-up of metabolic processes, long-term tests of hepatotoxicity and enzyme activity induction potential of drugs.</p>

Journal

References(41)*help

See more

Keywords

Details 詳細情報について

Report a problem

Back to top