TABLE 2.
Selected hepatotoxin screening using 3D hepatic models established with different cell types.
| Cell type | Culture paradigm | Drug exposure period | Endpoints | References |
|---|---|---|---|---|
| PHHs | MPCC co-culture | 9 days | Albumin, urea, and glutathione levels and cellular ATP content | Khetani et al. (2013) |
| PHHs | Spheroid co-culture | 14 days | Cellular ATP content | Proctor et al. (2017) |
| PHHs | Spheroid mono-culture | 14 days | Cellular ATP content | Li et al. (2020) |
| PHHs | Spheroid mono-culture | 14 days | Cellular ATP content | Vorrink et al. (2018) |
| PHHs | Spheroid mono-culture | 28 days | Cellular ATP content | Bell et al. (2016) |
| PHHs | MPCC co-culture | 14 days | Cell viability | Ware et al. (2017) |
| Albumin secretion | ||||
| Urea synthesis | ||||
| CYP3A4 activity | ||||
| Global gene expression profiles | ||||
| HepG2 | Spheroid mono-culture | 6 days | Oxidative stress response pathway | Hiemstra et al. (2019) |
| UPR pathway | ||||
| DNA damage response pathway | ||||
| HepaRG | Spheroid mono-culture | 6 days | Cellular ATP content | Ramaiahgari et al. (2017) |
| HepaRG | Spheroid mono-culture | 7 days | Cellular ATP content | Ott et al. (2017) |
| CYP1A and CYP3A4 activity | ||||
| hiPSC-HLCs; hESC-HLCs; HepG2 | Spheroid mono-culture | 24 h | Cell viability | Takayama et al. (2013) |
| hiPSC-HLCs; hESC-HLCs | Organoid mono-lineage | 72 h | Cell viability | Shinozawa et al. (2021) |
| Cholestatic function | ||||
| Mitochondrial toxicity |
PHHs, primary human hepatocytes; MPCC, micropatterned co-culture; hESCs, human embryonic stem cells; hiPSCs, human induced pluripotent stem cells; HLCs, hepatocyte-like cells.