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

Table 1 Metabolic dysfunction-associated steatotic liver disease model construction and phenotypic recapitulation in liver organoids derived from human pluripotent stem cells

Cellular origin	Cell types	Model induction method	Phenotype reproduced	Ref.
hESCs	Hepatocyte-like, cholangiocyte-like	200/500 μM OA and PA for 4-14 days	Time- and dose-dependent elevation of lipid accumulation, ROS, and lipid peroxidation, accompanied by bile canaliculi network decay and ductular reactions	Ramli et al[11], 2020
hESCs	Hepatocyte-like	450 μM FFA (OA:PA = 2:1) for 2 days	Disrupted glucose/Lipid metabolism, oxidative stress, apoptosis, loss of polarization, impaired liver function, and ductular reaction	Qin et al[12], 2025
hiPSCs	Hepatocyte-like, KC-like, HSC-like	200/400/800 μM OA for 3-7 days	Steatosis, inflammation, and fibrosis	Ouchi et al[14], 2019
hESCs	Hepatocyte-like, liver sinusoidal endothelial cell-like	450 μM OA and 150 μM PA for 24/48 hours	Pericentral organoids from liver lobules exhibit faster and greater lipid droplet accumulation than periportal organoids	Zhang et al[15], 2025
hPSCs	Hepatocyte-like, cholangiocyte-like, HSC-like	10 ng/mL and 25 ng/mL TGF-β1/500 μM OA/500 μM PA for 4 days	OA induces benign steatosis; PA induces inflammatory changes of steatohepatitis; TGF-β1 induces steatohepatitis and fibrosis most prominently	Hess et al[16], 2023
hiPSCs	Hepatocyte-like, HSC-like, biliary-like	500 μM OA for 4 days, followed by treatment with 500 μM OA combined with 25 ng/mL TGF-β for another 3 days	Severe steatosis, oxidative stress, mitochondrial dysfunction, inflammation, and fibrosis as progressive characteristics of human MASH	Wu et al[17], 2024
hiPSCs	Hepatocyte-like, cholangiocyte-like	500 μM OA for 3 days	Increased lipid droplet accumulation, upregulated expression of fibrosis and lipid metabolism markers in higher stiffness matrices	Liu et al[18], 2025
hiPSCs	Hepatocyte-like, cholangiocyte-like	600 μM FFA (OA:PA = 2:1) for 7 days	Lipid accumulation, ROS production and up-regulated expression of inflammatory and fibrotic markers	Wang et al[20], 2020
hiPSCs and liver stem cells	Hepatocytes, cholangiocyte-like, KC-like, HSC-like	450 μM OA, 150 μM PA, 100 mmol/L fructose for 3 days, followed by addition of 10 ng/mL lipopolysaccharide and 10 mmol/L phenylacetic acid another 3/5 days	Steatosis, hepatocellular ballooning, inflammatory and fibrogenic microenvironment	Balachander et al[21], 2025
hiPSCs	Hepatocyte-like, cholangiocyte-like	400 μM OA and 200 μM PA for 48 hours	Dysregulated lipid metabolism, increased inflammatory factor secretion, and fibrosis	You et al[22], 2026

hESCs: Human embryonic stem cells; OA: Oleic acid; PA: Palmitic acid; ROS: Reactive oxygen species; FFA: Free fatty acids; hiPSCs: Human induced pluripotent stem cells; KC: Kupffer cell; HSC: Hepatic stellate cell; TGF-β: Transforming growth factor-β; MASH: Metabolic dysfunction-associated steatohepatitis; hPSCs: Human pluripotent stem cells.