Publication Summary:

Nonalcoholic fatty liver disease (NAFLD) is a chronic condition that originates as lipid accumulation within hepatocytes (steatosis) and progresses into nonalcoholic steatohepatitis (NASH), characterized by lipid accumulation, inflammation, oxidative stress, and fibrosis. NAFLD is now recognized as the most common cause of chronic liver disease in the western world, with an estimated prevalence of 25% worldwide, and is projected to become the leading indication for liver transplant by 2025. Despite decades of research, the mechanisms of NAFLD progression, therapeutic approaches and non-invasive diagnostics are still resoundingly absent. The study of steatosis and NASH has traditionally utilized rodent models, which are time consuming to generate and do not fully recapitulate the complex phenotypes associated with the human disease. Furthermore, current 2D cell culture models lack relevant liver cell types, do not accurately display diseased phenotypes, and have limited utility due to rapid loss of cell viability and function. To date, there are no current models exploring the role of cell donor heterogeneity and its impact on disease phenotype and the progression of disease. Thus, there is a significant need for a more predictive human multicellular 3D in vitro model to study the progression of steatosis into NASH.