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Three-dimensional human cell culture model for studying Non-Alcoholic Fatty Liver Disease
The European Association for Study of the Liver (EASL)
Filed under: Disease modeling and NAFLD/NASH
Kostrzewski et al
Non-Alcoholic Fatty Liver Disease (NAFLD) is a growing concern worldwide and is set to become the most predominant cause of chronic liver disease. NAFLD describes a range of disease states from liver steatosis, which is the simplest and most common through to late-stage liver disease, cirrhosis, and liver cancer. There are currently no FDA-approved drugs for the treatment of NAFLD and there is a clear requirement for better models to understand disease progression and the molecular pathways underlying the disease. Currently available pre-clinical models, be it in vivo or in vitro, have a number of limitations and differ in regards to the degree of hepatocellular damage and metabolic alterations associated with disease development. Current in vitro models generally utilizes hepatocellular carcinoma-derived cell lines, which lack many of the biochemical properties of primary hepatocytes and fail to represent the complexity of the liver microenvironment and disease pathology.
Here, we developed a fully human in vitro NAFLD model by culturing human hepatocytes in 3D. This model mimics the liver microarchitecture and supports hepatic functions over extended periods of culture, allowing the continual accumulation of fat deposits in the hepatocytes.