Table 5.
Comparison of LoC platforms against IQ-MPS phase I guidelines.
LoC model | Maximum albumin synthesis value (μg/day/million cells) (study duration) | Maximum urea synthesis value (μg/day/million cells) (study duration) | Gene expression of enzymes and transporters (comparison with freshly thawed hepatocytes) | Reference |
---|---|---|---|---|
Matrix free iHep-on-chips | 0.1 (35 days) | 6 (35 days) | Gene expression reported only for CYP3A4, CYP2B6, CYP2C9 (comparison not reported) | [51] |
PHH sandwich culture-on-chips (with LSEC) (Emulate) | 60 (14 days) | Not reported | Gene expression not reported, CYP activity compared (CYP3A and CYP2B higher, CYP1A lower than fresh hepatocytes) |
[55] |
PHH sandwich culture-on-chips (with LSEC, stellate cells, and kupffer cells) (Emulate) | 60 (7 days) (donor 2) | 250 (7 days) (donor 2) | Gene expression reported (CYP3A4 significantly higher, 13 out of 17 genes with higher expression than fresh hepatocytes) | [13] |
3D microtissues-on-chips (CN Bio) | 50 (19 days) | Not reported | Gene expression reported for metabolic enzymes and CYP3A4 activity was also measured (comparison not reported) | [29] |
iHep-on-chips (with endothelial cells and THP-1 cells) (Mimetas) | 15-20 (15–17 days) | 20-40 (15–17 days) | Gene expression not reported but measured metabolic activity (comparison not reported) | [70,76] |
PHH sandwich culture-on-chips (Javelin Biotech) | 40 (15 days) | 160 (15 days) | Reported stable gene expression for 15 days and measured CYP450 activity (comparison not reported) | [81] |