Table 2 Different hepatocyte-like cell models for hepatotoxicity testing
From: Advancements in stem cell-derived hepatocyte-like cell models for hepatotoxicity testing
Models | Descriptions | Advantages | Disadvantages | Applications | References |
|---|---|---|---|---|---|
2D monolayer cell culture | Cells adhere to a solid and flat surface | Easy and low-cost operation | Poor cell–cell and cell–matrix interactions, far different from the environment in vivo, limited enzyme activity | Evaluation of drug metabolism and toxicity, drug–drug interactions, high-throughput drug screening, long-term drug toxicity assessment | |
Complex organoids | Organoids with multiple cell types | Presence of non-parenchymal cells, rich and complex structure | Poor homogeneity and controllability | Specific disease models | |
Simplified organoids | Organoids with single-cell type | Good homogeneity and controllability | Relatively simple structure and function | Large-scale drug screening | |
Scaffold-based organoids | Organoids grown in supportive scaffold | Efficient differentiation, intact vasculature, controllable size, shape, permeability, and porosity | Undefined components, lower stability and repeatability, problems of biocompatibility and cytotoxicity, absorption of test compound by scaffold | Studies of drug metabolism, disease modeling, and implantation in vivo | |
Scaffold-free organoids | Cells self-aggregate to form organoids | Simple operation, low-cost, high throughput, no compatibility issues, cell–cell and cell–matrix interaction, nutrition, oxygen gradient formation | Hypoxia and necrosis in the center of the organoids | Large-scale drug screening | |
Patient-derived organoids | Organoids with patient-specific cells | Donor-specific CYP metabolism and drug responses | Relatively complex operation | Disease modeling, mechanism research, targeted drug screening | |
Organ-on-a-chip | Organ biomimetic system with organoids grown in a microfluidic chip | Precise and dynamic control of the cellular microenvironment | High-cost, complex operation, need of sophisticated equipment | Prediction of drug absorption, metabolism, and clearance | |
Chimeric mice with humanized livers | Mouse liver cells are replaced by human hepatocytes | Possessing human drug metabolism and transformation functions, good human relevance | High-cost, time-consuming operation, varying degree of humanization, immune-compromised | Preclinical drug evaluation |