Toxicity evaluation by high content analysis of 3D cultured primary human hepatocytes
Full Title
Toxicity evaluation by high content analysis of 3D cultured primary human hepatocytes
Authors
Toshimasa Ito, Kazuhiro Fujimoto, Ryo Fujino, Masato Kobayashi, Miki Fujishima, Tsutomu Negama
Pharmaceutical Sciences Division, Business Management Unit, SEKISUI MEDICAL CO., LTD.
Presented at the Japanese Society of Toxicology (JSOT) 2020 Annual Meeting
Abstract
DILI is one of the major reasons for drug discontinuation and withdrawal from the market, therefore highly predictive toxicity model is desired. The development of liver toxicity is mediated by a variety of mechanisms, making it difficult to predict from a single biomarker. In these circumstances, we attempted to improve in vitro model for DILI detection by conducting High Content Analysis using primary human hepatocyte(PHH ) spheroids formed in methylcellulose medium which can be expected to maintain CYP activity for a long time after cell seeding. Spheroids were exposed to multiple drugs causing DILI and were comprehensively evaluated using various toxicity biomarkers. Furthermore we made HepG2 spheroid and compared with PHH spheroid’s character.