Figure 6.

Zonation of primary (a) rat and (b) human hepatocytes in drug-induced liver toxicity in the MPOC platform. After 24 hours induction with a gradient of 3-MC (one inlet: 0 μM 3-MC and the other inlet: 2 μM 3-MC) at a flow rate of 120 µL/hr, cells were uniformly exposed to a dose of 10 mM acetaminophen (APAP) for 4 hours. Cells were stained with TMRM. The non-induced hepatocytes remained viable while the 3-MC induced hepatocytes relatively lost their viability. The gradient of the acetaminophen-related hepatotoxicity was demonstrated by checking cell viability in CYP activity-dependent response to acetaminophen dose. A gradient of cell viability across the width of the device was estimated through quantification of viability using Image J. (a) All data met p < 0.05 except that non-induced vs ch1, non-induced vs ch2, non-induced vs ch3, ch1 vs ch2, ch1 vs ch3, ch2 vs ch3, ch2 vs ch4, ch3 vs ch4, ch3 vs ch5, and ch4 vs ch5 are not significant (ANOVA n = 5, Tukey’s test). (b) All data met p < 0.05 except that non-induced vs ch1, non-induced vs ch2, ch1 vs ch2, ch2 vs ch3, ch3 vs ch4, ch3 vs ch5, and ch4 vs ch5 are not significant (ANOVA n = 4, Tukey’s test). Each experiment was replicated using at least three different cell pools. Scale bar: 400 µm.