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

Table 4 Metabolic dysfunction-associated steatotic liver disease model construction and phenotypic recapitulation in liver organoids derived from immortalized cell lines

Cellular origin	Cell types	Model induction method	Phenotype reproduced	Ref.
HepG2 (PNPLA3 I148M homozygous):LX-2 = 24:1	Hepatocytes, HSC	500 μM FFA (OA:PA = 2:1) for 48 hours	Lipid accumulation and fibrosis	Pingitore et al[68], 2019
HepaRG	Hepatocytes, cholangiocytes	500 μM FFA (OA:PA = 1:1) for 48 hours	Lipid accumulation, impaired glucose regulation, and reduced Akt phosphorylation	Teng et al[69], 2021
HepaRG:primary human macrophages:LX-2 = 8:1:1	Hepatocytes, cholangiocytes, HSC, KC	150 μM stearic acid and 300 μM OA for 9 days	Steatosis, increased expression of fibrosis markers and pro-inflammatory cytokines	Bronsard et al[70], 2024; Duclos et al[71], 2026

HSC: Hepatic stellate cell; FFA: Free fatty acids; OA: Oleic acid; PA: Palmitic acid; KC: Kupffer cell.