Comparison of the sensitivity of organotypic liver models
| Cell Model | Cell Type | Mono-/Coculture | Exposure Regimen | Exposure Time | TC50 | Reference |
|---|---|---|---|---|---|---|
| Toxicity Mechanism: Reactive Metabolites Acetaminophen (Cmax = 0.136 mM; TC50 in mM) | ||||||
| Spheroid | PHH | Monoculture | Repeated | 14 days | 0.32–0.8 | (Bell et al., 2018) |
| Spheroid | PHH | Monoculture | Repeated | 14 days | 0.46 | (Bell et al., 2020) |
| Spheroid | PHH | Coculture with NPCs | Repeated | 14 days | ∼0.5 | (Richert et al., 2016) |
| Spheroid | PHH | Coculture with NPCs | Repeated | 14 days | 0.57 | (Proctor et al., 2017) |
| Spheroid | PHH | Coculture with Kupffer cells | Repeated | 14 days | ∼0.6 | (Richert et al., 2016) |
| Spheroid | PHH | Monoculture | Repeated | 14 days | 0.64 | (Bell et al., 2017) |
| Spheroid | PHH | Coculture with NPCs | Repeated | 14 days | 0.75 | (Messner et al., 2013) |
| Spheroid | PHH | Monoculture | Repeated | 14 days | 0.88 | (Hendriks et al., 2016) |
| Spheroid | PHH | Monoculture | Single | 24 h | 0.93 | (Li et al., 2020) |
| Spheroid | HepaRG | Monoculture | Repeated | 14 days | 1.1 | (Hendriks et al., 2016) |
| Spheroid | HepaRG | Monoculture | Single | 24 h | ∼1.1 | (Leite et al., 2012) |
| Spheroid | PHH | Monoculture | Repeated | 96 h | 1.21 | (Bell et al., 2020) |
| Spheroid | PHH | Monoculture | Repeated | 8 days | 1.3 | (Hendriks et al., 2016) |
| Spheroid | PHH | Coculture with NPCs | Repeated | 14 days | 1.35 | (Bell et al., 2020) |
| Spheroid | HepaRG | Monoculture | Repeated | 8 days | 1.8 | (Hendriks et al., 2016) |
| Spheroid | PHH | Coculture with NPCs | Repeated | 10 days | 1.7 | (Foster et al., 2019) |
| Spheroid | PHH | Coculture with Kupffer cells | Single | 5 days | 2.25 | (Li et al., 2020) |
| Perfused liver-chip | PHH | Coculture with LSECs | Repeated | 10 days | 2.4 | (Foster et al., 2019) |
| Spheroid | PHH | Coculture with NPCs | Repeated | 96 h | 2.46 | (Bell et al., 2020) |
| Spheroid | HepaRG | Monoculture | Single | 24 h | 2.48 | (Wang et al., 2016) |
| Spheroid | HepaRG | Monoculture | Single | 24 h | 2.7 | (Gunness et al., 2013) |
| Spheroid | HepaRG | Monoculture | Repeated | 6 days | 2.879 | (Ramaiahgari et al., 2017) |
| Spheroid | PHH | Monoculture | Single | 5 days | 3.28 | (Li et al., 2020) |
| Spheroid | HepaRG | Monoculture | Repeated | 7 days | ∼4 | (Liu et al., 2018a) |
| MPCC | iPSC-HLC | Monoculture | Repeated | 6 days | 4.48 | (Ware et al., 2015) |
| Perfused liver-chip | PHH | Coculture with NPCs | Repeated | 14 days | 5.59 | (Novik et al., 2017) |
| Spheroid | HepG2 | Monoculture | Repeated | 4 days | 7.21 | (Gaskell et al., 2016) |
| Spheroid | HepaRG | Monoculture | Single | 24 h | 7.62 | (Wang et al., 2015) |
| Spheroid | HepG2 | Monoculture | Repeated | 6 days | ∼9.4 | (Ramaiahgari et al., 2014) |
| Spheroid | hiPSC/hESC-HLC | Monoculture | Single | 24 h | >10 | (Tasnim et al., 2016) |
| Spheroid | hiPSC-HLC | Monoculture | Single | 24 h | >20 | (Takayama et al., 2013) |
| Spheroid | HepG2 | Monoculture | Single | 24 h | >20 | (Takayama et al., 2013) |
| MPCC | PHH | Monoculture | Single | 24 h | 35 | (Khetani and Bhatia, 2008) |
| Spheroid | HepG2 | Monoculture | Single | 24 h | 40 | (Fey and Wrzesinski, 2012) |
| Toxicity Mechanism: Inhibition of Mitochondrial Respiration Amiodarone (Cmax = 5 μM; TC50 in μM) | ||||||
| Spheroid | PHH | Monoculture | Repeated | 28 days | 1.6 | (Bell et al., 2016) |
| Spheroid | PHH | Monoculture | Repeated | 14 days | 6.5 | (Bell et al., 2016) |
| Perfused liver-chip | PHH | Coculture with NPCs | Repeated | 14 days | 9 | (Novik et al., 2017) |
| Spheroid | PHH | Monoculture | Repeated | 14 days | 12 | (Bell et al., 2017) |
| Spheroid | PHH | Monoculture | Repeated | 14 days | 12 | (Hendriks et al., 2016) |
| MPCC | PHH | Monoculture | Repeated | 14 days | 14 | (Khetani et al., 2013) |
| Spheroid | hiPSC-HLC | Monoculture | Single | 24 h | >25 | (Takayama et al., 2013) |
| Spheroid | PHH | Monoculture | Single | 5 days | 26 | (Li et al., 2020) |
| Spheroid | PHH | Coculture with NPCs | Repeated | 14 days | 32 | (Proctor et al., 2017) |
| Spheroid | HepaRG | Monoculture | Single | 7 days | 49 | (Ott et al., 2017) |
| Spheroid | HepG2 | Monoculture | Single | 24 h | ∼50 | (Takayama et al., 2013) |
| Spheroid | PHH | Coculture with NPCs | Repeated | 14 days | ∼60 | (Richert et al., 2016) |
| Spheroid | HepaRG | Monoculture | Single | 24 h | 83 | (Ott et al., 2017) |
| Spheroid | HepaRG | Monoculture | Single | 24 h | 178 | (Mueller et al., 2014) |
| Spheroid | HepG2 | Monoculture | Single | 24 h | >200 | (Mueller et al., 2014) |
| Spheroid | HepG2 | Monoculture | Single | 24 h | 260 | (Fey and Wrzesinski, 2012) |
| Toxicity Mechanism: Cholestasis Chlorpromazine (Cmax = 0.84 μM; TC50 in μM) | ||||||
| Spheroid | PHH | Monoculture | Single | 5 days | 4.4 | (Li et al., 2020) |
| Spheroid | PHH | Monoculture | Repeated | 14 days | 4.6 | (Bell et al., 2017) |
| Spheroid | PHH | Coculture with NPCs | Repeated | 14 days | ∼7 | (Proctor et al., 2017) |
| Spheroid | PHH | Coculture with only kupffer cells | Repeated | 14 days | ∼9 | (Richert et al., 2016) |
| Spheroid | PHH | Coculture with NPCs | Repeated | 14 days | ∼10 | (Richert et al., 2016) |
| Spheroid | PHH | Monoculture | Repeated | 14 days | 11 | (Hendriks et al., 2016) |
| Spheroid | PHH | Monoculture | Repeated | 8 days | 13 | (Hendriks et al., 2016) |
| Spheroid | HepaRG | Monoculture | Repeated | 14 days | 13 | (Hendriks et al., 2016) |
| Spheroid | HepaRG | Monoculture | Repeated | 8 days | 16 | (Hendriks et al., 2016) |
| Perfused liver-chip | PHH | Coculture with NPCs | Repeated | 14 days | 28 | (Novik et al., 2017) |
| Spheroid | HepaRG | Monoculture | Repeated | 7 days | ∼40 | (Liu et al., 2018a) |
| Spheroid | HepG2 | Monoculture | Single | 24 h | 43 | (Mueller et al., 2014) |
| Spheroid | HepaRG | Monoculture | Single | 24 h | 98 | (Mueller et al., 2014) |
| MPCC | PHH | Monoculture | Single | 24 h | 100 | (Khetani and Bhatia, 2008) |
| Spheroid | HepaRG | Monoculture | Single | 24 h | 120 | (Wang et al., 2015) |
| Toxicity Mechanism: Mitochondrial Depletion Fialuridine (Cmax = 0.64 μM; TC50 in μM) | ||||||
| Spheroid | PHH | Monoculture | Repeated | 28 days | 0.1 | (Bell et al., 2016) |
| Spheroid | PHH | Monoculture | Repeated | 32 days | 0.28 | (Hendriks et al., 2019) |
| Spheroid | PHH | Monoculture | Repeated | 14 days | 0.7 | (Bell et al., 2016) |
| Spheroid | PHH | Monoculture | Repeated | 14 days | ∼3 | (Bell et al., 2018) |
| Spheroid | PHH | Monoculture | Repeated | 7 days | 7.86 | (Hendriks et al., 2019) |
| Spheroid | PHH | Coculture with NPCs | Repeated | 10 days | 77 | (Foster et al., 2019) |
| Perfused liver-chip | PHH | Coculture with LSECs | Repeated | 10 days | 84 | (Foster et al., 2019) |
| Spheroid | PHH | Coculture with NPCs | Repeated | 14 days | >100 | (Richert et al., 2016) |
| Spheroid | HepG2 | Monoculture | Repeated | 4 days | 200 | (Gaskell et al., 2016) |
hESC, human embryonic stem cell.