Several studies have demonstrated the appropriateness of 3D organoid cultures over the conventional 2D cultures, the advantages of 3D models include replicating the complex attributes of the liver beyond liver-specific metabolism, such as increased cell density, organisation, cell-cell signalling, and O2 zonation. In this project we will establish a novel in-vitro 3D model to study hepatocyte biology in the context of liver disease. A more comprehensive approach to investigating the intercellular mechanisms of NAFLD will include co-culture of organoids with other cell types, stellate cells, Kupffer cells, and other inflammatory cells.
The overall aims of this project are to optimise the preparation of liver organoids from mouse and human liver tissue, to assess changes in cell function and signalling in response to liver injury-causing agents including thioacetamide and to optimise methods of optimal targeting of specific genes in the organoids.
The expected outcome from this project is the generation of 3D organoid cultures from human and mouse livers which can be used for understanding disease mechanisms and be used for drug and therapeutic testing.