|
| Model | Benefits | Limitations | Example references |
|
| Conventional cultures/cocultures | (i) High-throughput
(ii) Sandwich cultures can maintain cell polarity | (i) Usually lack liver stromal cells
(ii) Loss of drug metabolizing capacity occurs within hours | [6, 10–13] |
|
Micropatterned
cocultures | (i) Controlled architecture allows for higher functions for 1-2 months
(ii) Coculture allows for the study of drug toxicity in a diseased background
(iii) Compatible with high content imaging readouts | (i) Usually lack all liver stromal cells
(ii) Use nonhuman supporting cells | [14, 17, 18, 20, 27] |
|
| Spheroidal cultures/cocultures | (i) Multicellular interactions
(ii) Maintenance of major liver functions for 1–3 months | (i) Difficult to control disorganized cell type interactions over time
(ii) Necrosis in center of larger spheroids
(iii) Size variability
(iv) Incompatible with standard high content imaging equipment | [30–38] |
|
| Bioprinted cultures/cocultures | (i) Precise control of cell placement
(ii) Multicellular interactions | (i) Printing resolution does not allow placement of individual cells
(ii) Low-throughput
(iii) Heterogeneous distribution of drugs across the bioprinted tissues | [39, 53, 54] |
|
| Perfused biochips | (i) Dynamic fluid flow for nutrient and waste exchange
(ii) Sustained functionality for at least 1 month
(iii) Can be combined with module for real-time toxicity endpoint readouts | (i) Binding of drugs to tubing
(ii) Large dead volume requiring higher quantities of novel compounds
(iii) Low-throughput
(iv) Shear stress may cause lower hepatic functions
(v) Can wash away built-up beneficial molecules | [44–52, 55–66] |
|
| Precision cut liver slices | (i) Retains native liver architecture and all liver cell types
(ii) Can be combined with flow to improve functional lifetime | (i) Low-throughput
(ii) Rapid decline in liver functions
(iii) Heterogeneous distribution of drug within the slice | [67–72] |
|
| Humanized rodents | (i) Human-relevant toxicity profiles in vivo
(ii) Can look at organ-organ interactions with a humanized liver background | (i) Variability in human hepatocyte engraftment efficiency
(ii) Low-throughput
(iii) Residual murine liver cells can cause confounding results
(iv) Interactions with murine organs | [73–85] |
|
