Table 3.
Comparative overview of the sensitivity of human organotypic liver models to acetaminophen-induced hepatotoxicity.
| Cell model | Cell type | Scaffold | Single/repeated exposure | Exposure time | Mono-/co-culture | TC50 (mM) | Reference |
|---|---|---|---|---|---|---|---|
| Spheroid | PHH | No | Repeated | 14 days | Monoculture | 0.32–0.8 | (Bell et al., 2018) |
| Spheroid | PHH | No | Repeated | 14 days | Co-culture with NPCs | 0.57 | (Proctor et al., 2017) |
| Spheroid | PHH | No | Repeated | 14 days | Monoculture | 0.64 | (Bell et al., 2017) |
| Spheroid | PHH | No | Repeated | 14 days | Co-culture with NPCs | 0.75 | (Messner et al., 2013) |
| Spheroid | HepaRG | No | Single | 24 h | Monoculture | ∼1.1 | (Leite et al., 2016) |
| Spheroid | PHH | No | Repeated | 8 days | Monoculture | 1.3 | (Hendriks et al., 2016) |
| Spheroid | HepaRG | No | Repeated | 8 days | Monoculture | 1.8 | (Hendriks et al., 2016) |
| Spheroid | PHH | No | Repeated | 10 days | Co-culture with NPCs | 1.7 | (Foster et al., 2019) |
| Perfused liver chip | PHH | Rat tail collagen-I | Repeated | 10 days | Co-culture with LSECs | 2.4 | (Foster et al., 2019) |
| Spheroid | HepaRG | PEGDA | Single | 24 h | Monoculture | 2.48 | (Wang et al., 2016) |
| Spheroid | HepaRG | No | Single | 24 h | Monoculture | 2.7 | (Gunness et al., 2013) |
| Spheroid | HepaRG | No | Repeated | 6 days | Monoculture | 2.879 | (Ramaiahgari et al., 2017) |
| Spheroid | HepaRG | Liver biomatrix | Repeated | 7 days | Monoculture | ∼4 | (Liu et al., 2018) |
| MPCC | hiPSC-HLC | Rat tail collagen-I | Repeated | 6 days | Co-culture with mouse fibroblasts | 4.48 | (Ware et al., 2015) |
| Perfused liver chip | PHH | Rat tail collagen-I | Repeated | 13 days | Co-culture with NPCs | 5.59 | (Novik et al., 2017) |
| Spheroid | HepG2 | No | Repeated | 4 days | Monoculture | 7.21 | (Gaskell et al., 2016) |
| Spheroid | HepaRG | No | Single | 24 h | Monoculture | 7.62 | (Wang et al., 2015) |
| Spheroid | HepG2 | Hydrogel | Repeated | 6 days | Monoculture | ∼9.4 | (Ramaiahgari et al., 2014) |
| Spheroid | hiPSC/hESC-HLC | Galactosylated cellulosic sponge | Single | 24 h | Monoculture | >10 | (Tasnim et al., 2016) |
| Spheroid | hiPSC-HLC | No | Single | 24 h | Monoculture | >20 | (Takayama et al., 2013) |
| Spheroid | HepG2 | No | Single | 24 h | Monoculture | >20 | (Takayama et al., 2013) |
| MPCC | PHH | Rat tail collagen-I | Single | 24 h | Co-culture with mouse fibroblasts | 35 | (Khetani and Bhatia, 2008) |
| Spheroid | HepG2 | No | Single | 24 h | Monoculture | 40 | (Fey and Wrzesinski, 2012) |
Studies are sorted by descending sensitivity. HLC, hepatocyte-like cell; LSEC, liver sinusoidal endothelial cells; NPC, non-parenchymal cell; PHH, primary human hepatocytes; PEGDA, poly-ethylene-glycol-diacrylate.