Creation of Robust In Vitro Models to Study Liver Dis-ease

We have developed in vitro models to study liver disease, such as liver inflammation and fibrosis, as seen in non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD/ NASH); or hepatitis viral infection; or to enhance our ability to detect drugs that cause acute or repeat dose drug induced liver injury (DILI) assessment, and this in medium to high throughput format. This requires that the model consist at least of (i) longer-term stable functioning hepatocytes that can be damaged by a compound /insult; resident macrophages (KCs); and hepatic stellate cells (HSCs) that can respond to this dam-age. In addition, the cells would ideally also contain stress reporter genes to allow high-content image-based definition of cell stress. Finally, the model should be down-scalable to 96 (or 384) well format allowing drug screening. Data will be presented describing studies towards this goal starting from induced pluripotent stem cells.