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  • Long-term maintenance of functional primary human hepatocytes using small molecules.

Long-term maintenance of functional primary human hepatocytes using small molecules.

FEBS letters (2019-08-23)
Takeshi Katsuda, Masaki Kawamata, Ayako Inoue, Tomoko Yamaguchi, Maki Abe, Takahiro Ochiya
ABSTRACT

The immediate deterioration of primary human hepatocytes (PHHs) during culture limits their utility in drug discovery studies. Here, we report that a cocktail of four small molecule signaling inhibitors, termed YPAC, is useful for maintaining various hepatic functions of PHHs, including albumin and urea productivity, glycogen storage, and cytochrome P450 (CYP) expression. Most importantly, we found that YPAC allows PHHs to retain enzymatic activities of CYP1A2, CYP2B6, and CYP3A4 even after 40 days of culture, and that inducibility of CYP3A4 activity in response to the prototypical inducers rifampicin and phenobarbital is also maintained. Our novel approach could facilitate drug discovery studies.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Cyp7a1 Antibody, clone 15B9.1, clone 15B9.1, from mouse
Sigma-Aldrich
Anti-Actin Antibody, clone C4, ascites fluid, clone C4, Chemicon®