Table 1.

Overview of 3D Liver models.

References	Cell sources	Cell types represented	Characteristics/ Functionality	Applications/Model use	Advantages	Limitations	Developmental stage
Coll et al. (88)	iPSC HepaRG	•Stellate cell •Hepatocyte	•Retinol Storage •Activatable HSCs •ECM production •Drug metabolism	•Fibrosis response •Toxicity	•Improved phenotype of both cell types over mono culture	•Use of cell line as parenchyma •No tissue-like organization	•Lipid storage and quiescent phenotype suggests mature HSC function •Omics reveals differences to primary cells
Takebe et al. (17)	iPSC	•Hepatocyte •Endothelial cell •Mesenchyme	•Broad hepatocyte function (e.g., metabolism, protein secretion) •Functional vasculature	•Source of potentially transplantable organs, survival improvement after liver failure	•Vascular network •Multiple cell types •Scalable production	•Function relies on in vivo transplantation •Lack of biliary or kupffer cell types	•Formed at an early hepatic endoderm stage, followed by subsequent in vivo functional maturation
Wu et al. (89)	iPSC	•Hepatocyte •Cholangiocyte •Endothelial cell	•Organized BEC and bile acid production •Hepatocyte functions	•Hepatobiliary functions	•Multiple cell types capable of structure formation and coordinated function	•Low levels of hepatocyte function	•Fetal liver-like organization and functional level
Guan et al. (90)	iPSC	•Hepatocyte •Cholangiocyte •Mesenchymal cell (low abundance)	•Secondary organoid formation •Broad hepatocyte function (bile acid and albumin secretion, CYP metabolism, etc.)	•Liver development and regeneration •Biliary disease-ALGS	•Expandable by secondary organoid formation due to progenitor population •Long term maintenance	•Some HSC activation in routine culture	•Similar to PHH and liver tissue by transcriptome analysis
Ouchi et at. (91)	iPSC	•Hepatocyte •Stellate cell •Cholangiocyte •Kupffer cell	•CYP3A4 expression •Vitamin A storage •LPS response •Hepatocyte lipid accumulation •HSC activation	•NAFLD •Fibrosis response •Wolmans disease	•Multiple cell types •Capable of inflammatory response	•Low Kupffer cell number •Some HSC activation in routine culture •High inter-batch variability	•Fetal-like hepatocyte activity
Huch et al. (92)	Biliary Epithelial	•Hepatocyte •Cholangiocyte	•High CYP3A4 activity •Phase I and II metabolic activity	•A1AT deficiency •ALGS	•Genetically stable •Long term maintenance	•Only parenchymal cell model	•Mixed fetal and adult hepatocyte functions