SLAS 2019 Advanced 3D Human Models and High-Content Analysis Symposium

Steatosis, or the increased accumulation of lipids in the liver, can be induced by several factors including exposure to steatogenic drugs and through pertubations in lipid metabolism indicative of non-alcoholic fatty liver disease (NAFLD). Hepatic lipid accumulation is a key driver of morphological and functional changes to liver architecture that leads to the development of acute and chronic liver disease and fibrosis. We have developed a number of high content screening platforms to screen for drug induced steatosis using 2D HepG2 cells and 3D HepG2 C3A spheroid cultures with detection of lipid accumulation by LipidTOX green and Nile red.Additionally, we have adapted our 3D spheroid platform to evaluate steatosis induced by dietary fatty acid uptake. We demonstrate our high throughput screening platforms utilising automated ECHO650 and Biomek NxP compound dispense combined with High Content Imaging of lipid accumulation using the ImageXpress Micro Confocal. Our assays are highly reproducible and have been validated using a panel of known steatogenic drugs. Development of such platforms will enable the early screening of candidates with steatogenic potential with a view to de-risking and de-selecting adverse compounds during the Discovery phase of drug development.