A micropatterned hepatocyte coculture model for assessment of liver toxicity using high-content imaging analysis.

The current landscape of in vitro models used to identify drug- or chemical-induced hepatotoxicity relies heavily on cell culture models consisting of HepG2, induced pluripotent stem cell-derived, or primary hepatocytes. While these in vitro models offer powerful approaches for predicting toxicity, each system has challenges, including variable metabolic capacity, brief ex vivo life span in culture, and adoption with standard automated microscopy high-content screening (HCS) systems to measure reproducibility data at the single-cell level. In this report we introduce a novel primary hepatocyte coculture model, HepatoPac™, as an alternative to current model systems for evaluation of in vitro hepatotoxicity in 96-well microtiter plate format examined by HCS.

Development of 3D dynamic flow model of human liver and its application to prediction of metabolic clearance of 7-ethoxycoumarin.

Primary and cryopreserved hepatocytes and immortalized hepatic cell lines in static two-dimensional monolayer culture format have been widely used as in vitro liver models for studies of xenobiotic metabolism, enzyme induction, hepatocyte regeneration, and hepatotoxicity. However, the tissue structure and metabolic capacity in these liver models are often ill-defined and are not well preserved compared to in vivo liver-specific architecture and functions. For this reason, we developed a three-dimensional (3D) dynamic flow model with primary human hepatocytes, which was optimized for cell seeding density, medium composition, and extracellular matrix proteins.