Organoids as preclinical platforms for metabolic dysfunction-associated steatotic liver disease: Model construction, mechanistic dissection, and therapeutic translation

Table 2 Metabolic dysfunction-associated steatotic liver disease model construction and phenotypic recapitulation in liver organoids derived from primary tissues

Cellular origin	Cell types	Model induction method	Phenotype reproduced	Ref.
Mice liver tissue	Mixture of cells from liver tissue	Mice fed with methionine-and choline-deficient diet for 4, 8, and 12 weeks	Liver fibrosis without lipid accumulation	Elbadawy et al[33], 2020
Mice liver tissue	Mixture of cells from liver tissue	245 μM OA and 122.5 μM PA for 48 hours	Lipid accumulation, increased liver fibrosis and inflammation	Zhou et al[34], 2024
Mice liver tissue and human fetal liver tissue	Mixture of cells from liver tissue	200 μM OA/150 μM OA and 150 μM PA for 3 days	Greater lipid accumulation in human vs mouse organoids	Liu et al[35], 2024
Adult stem cells from human liver tissue	Hepatocyte-like	600 μM OA for 3 days	Lipid accumulation, ROS production and inflammation	Zhu et al[36], 2025
Harbor residential bipotent progenitor cells from human liver tissue	Cholangiocyte-like, hepatocyte-like	Lactate/pyruvate/octanoic acid (10:1:2 mM; 15:1.5:3 mM) for 96 hours	Lipid accumulation, suppressed organoid growth, metabolic dysregulation, and mitochondrial impairment	Wang et al[37], 2022
Liver tissue from healthy individuals and MASLD patients and HLO: Primary human liver stellate cells = 5:1	Hepatocytes, cholangiocytes, stem cells, KC, HSC	750 μM PA for 72 hours	Steatosis, inflammation, and fibrosis	Goswami et al[38], 2025
Liver tissue from MASH patients	Hepatocytes, cholangiocytes	1.2 mmol/L and 2 mmol/L PA for 6 hours/2 mmol/L OA for 24 hours	MASH liver-derived organoids exhibit significantly reduced regenerative capacity, upregulated activity of multiple pathogenic pathways (inflammation, fibrosis, tumorigenesis), and greater susceptibility to PA-induced apoptosis and OA-induced lipid accumulation	McCarron et al[39], 2021

OA: Oleic acid; PA: Palmitic acid; ROS: Reactive oxygen species; MASLD: Metabolic dysfunction-associated steatotic liver disease; HLO: Human liver organoid; KC: Kupffer cell; HSC: Hepatic stellate cell; MASH: Metabolic dysfunction-associated steatohepatitis.