Authors:

Anna Catherine Dressman

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About Paper:

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a progressive liver disease characterized by excessive lipid accumulation in hepatocytes, leading to cellular dysfunction, inflammation, fibrosis, cirrhosis, and increased risk of hepatocellular carcinoma. Affecting nearly 25% of the global population, MASLD is projected to become the leading indication for liver transplantation. Traditional two-dimensional cultures have advanced our understanding of disease mechanisms at the cellular level, however, they are limited in replicating the complex architecture and dynamic cellular interactions present in vivo. To complement these models and enhance physiological relevance, we developed and assessed the capability of three-dimensional mouse and human liver organoid models to recapitulate key pathological features of MASLD, with a focus on hepatic lipid accumulation. Mouse liver organoids were generated from mouse hepatocytes and cultured under soluble conditions to maintain hepatic functionality. Human liver organoids were derived from induced pluripotent stem cell-derived hepatocyte progenitor cells by a two-step differentiation protocol. To induce lipid accumulation, organoids were exposed to varying concentrations of a 1:1 mixture of oleate and palmitate, mimicking the metabolic conditions observed in MASLD patients. Lipid deposition was quantified using Nile Red staining and lipid droplet analysis. Organoids treated with free fatty acids exhibited significantly increased lipid accumulation, validating their potential as an in vitro model for studying early disease pathogenesis. Future studies will focus on optimizing this model by integrating a liver- on-a-chip platform to better model additional pathological hallmarks of MASLD, advancing its utility for translational research and preclinical drug screening. Keywords: Organoids; Fatty Liver Disease; Free Fatty Acids; Lipids

Source:

Purdue University / 2025

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Co-authors:

Anna Catherine Dressman