Table 1.
Comparison of animal models, 2D monolayer cell culture models, and 3D liver organoid models.
| Model | Species | Type | Phenotype reproduced |
Advantages | Disadvantages |
|---|---|---|---|---|---|
| Animal models | Animal | SREBP-1c transgenic mice (141, 212) | Steatosis, Insulin resistance, Inflammation, Fibrosis | -Physiological environment -Immune system -Multiple cell types -Functionality -Structure -Metabolism |
-Non-human species -Low-throughput -High cost -Heterogeneous phenotypes (species, strain, gender) |
| PTEN null mice (142, 143) | Steatosis, Fibrosis | ||||
| Ob/ob mice (144, 213, 214) Db/db mice (146, 147, 215) |
Obesity, Steatosis, Insulin resistance, (Inflammation, Fibrosis) | ||||
| MAT1A null mice (216-218) |
Steatosis, Fibrosis | ||||
| High-fat diet mice (150, 219, 220) |
Obesity, Steatosis, Hepatic insulin resistance, Oxidative stress, Inflammation, Fibrosis |
||||
| Methionine- and choline-deficient diet mice (221-223) | Steatosis, Hepatic Insulin resistance, Inflammation, Oxidative stress, Mitochondrial damage, Apoptosis, Fibrosis | ||||
| Cholesterol and cholate diet mice (224) | Steatosis, Hepatic Insulin resistance, Inflammation, Oxidative stress, Fibrosis | ||||
| 2D monolayer cell culture models | Human | PHHs (155, 225) | Steatosis, ER stress, Apoptosis |
-Low cost -Easy handling -High-throughput compatibility -Easy downstream application |
-Limited physiological environment -Absence of non-parenchymal cell types - Absence of cell-to-cell and cell-to-matrix interactions -Low hepatic maturity |
| HepG2 (159, 226, 227) | Steatosis, Apoptosis, | ||||
| HuH 7 (159, 160, 228) | Steatosis, ER stress, Apoptosis, |
||||
| HepaRG (161, 229, 230) | Steatosis, Oxidative stress | ||||
| PSC-hepatocyte-like cells (162, 231) | Steatosis | ||||
| PSC-HSCs (232) | Inflammation, Activation of HSCs | ||||
| 3D liver organoid models | Human | Spheroids (3D coculture) (233-235) |
Steatosis, Activation of HSCs, Oxidative stress, Apoptosis, Inflammation, Expression of profibrotic markers, Mitochondrial dysfunction | -Complex structural organization -Long-term expansion -Multiple cell types -High/mid-throughput compatibility -Semi-physiological environment -Immune system |
-Complicated differentiation steps -Relatively high cost -Heterogeneity (batch variation) -Limited hepatic maturity |
| Monocellular liver organoids (from primary tissue) (176, 236, 237) |
Mainly steatosis | ||||
| Multi-tissue liver organoids (198, 199, 238) | Steatosis, HSC activation, Ductular reaction, Oxidative stress, Bile canaliculi disruption, Expression of profibrotic markers, Collagen secretion and deposition |