Significant efforts to identify non-invasive clinical biomarkers, and profile proteomic and transcriptomic changes at various stages of non-alcoholic steatohepatitis (NASH)* disease progression, have been made. But there is still much to learn about this multi-faceted disease and, after years of R&D, only one regulatory-approved therapeutic is currently available for its treatment.

A pressing need for more human-relevant pre-clinical tools to support therapeutic advancement has led to the development of Microphysiological systems (MPS) that more closely model the human liver and NASH.

Here, we describe a NASH MPS comprised of primary human hepatocytes (PHH) and non-parenchymal cells that form 3D microtissue structures when cultured together using our PhysioMimix® Organ-on-a-chip (OOC) System. We explore the model’s ability to recapitulate an advanced NASH phenotype, characterized by fibrosis, quantify the expression of biomarkers and its ability to assess the efficacy of four anti-NASH compounds that entered human clinical trials.

*NASH is also known as Metabolic dysfunction-associated steatohepatitis (MASH) following proposed nomenclature changes in 2023.