Modeling MASLD in a Dynamic Human Liver Microphysiological System

Metabolic dysfunction‑associated steatotic liver disease (MASLD) is the most prevalent chronic liver condition, affecting approximately 25% of the global population, yet human‑relevant in vitro models that recapitulate its metabolic and inflammatory complexity remain limited. MASLD is characterized by hepatic lipid accumulation and inflammation and can progress to cirrhosis or hepatocellular carcinoma. Current management strategies rely primarily on lifestyle and dietary modifications; however, poor adherence is associated with increased risk of disease progression. Therefore, the development of microphysiological MASLD models that better recapitulate human physiology is essential for advancing mechanistic insight and accelerating therapeutic discovery.

In this study, ATCC HepatoXcell™ Pro primary human hepatocytes were used to establish a MASLD model within a chip‑based microphysiological system for toxicology and pharmacokinetic applications. Cryopreserved hepatocytes were cultured under perfused conditions using maintenance media supplemented with optimized concentrations of palmitic and oleic acids to induce steatosis and inflammatory signaling while preserving cellular morphology and viability. Intracellular lipid accumulation was assessed by microscopic evaluation, while cytokine secretion was monitored to characterize inflammatory responses. Quantitative PCR was performed to assess expression of MASLD‑associated genes.

This approach enabled the consistent induction of steatotic and pro‑inflammatory phenotypes within a three‑dimensional, perfused liver tissue architecture. The resulting microphysiological MASLD model provides a human‑relevant in vitro platform for the mechanistic investigation of disease‑relevant pathways and for evaluating pharmacological response and compound‑induced hepatotoxicity.