Portal de Periódicos da CAPES

Utility of Three-Dimensional Cultures of Primary Human Hepatocytes (Spheroids) as Pharmacokinetic Models

2020; Multidisciplinary Digital Publishing Institute; Volume: 8; Issue: 10 Linguagem: Inglês

10.3390/biomedicines8100374

2227-9059

Kenta Mizoi, Hiroshi Arakawa, Kentarô Yano, Satoshi Koyama, Hajime Kojima, Takuo Ogihara,

Drug-Induced Hepatotoxicity and Protection

This paper reviews the usefulness, current status, and potential of primary human hepatocytes (PHHs) in three-dimensional (3D) cultures, also known as spheroids, in the field of pharmacokinetics (PK). Predicting PK and toxicity means pharmaceutical research can be conducted more efficiently. Various in vitro test systems using human hepatocytes have been proposed as tools to detect hepatic toxicity at an early stage in the drug development process. However, such evaluation requires long-term, low-level exposure to the test compound, and conventional screening systems such as PHHs in planar (2D) culture, in which the cells can only survive for a few days, are unsuitable for this purpose. In contrast, spheroids consisting of PHH are reported to retain the functional characteristics of human liver for at least 35 days. Here, we introduce a fundamental PK and toxicity assessment model of PHH spheroids and describe their applications for assessing species-specific metabolism, enzyme induction, and toxicity, focusing on our own work in these areas. The studies outlined in this paper may provide important information for pharmaceutical companies to reduce termination of development of drug candidates.