Fig. 2

Modeling DILI with diverse phenotypes using HLOs. A Albumin secretion after administration of APAP at 0.5, 3, or 10 mM for 7 days in HLOs. n = 3, *P < 0.05. B ATP content analysis after administration of APAP at 0.5, 3, or 10 mM for 7 days in HLOs. n = 3, *P < 0.05. C Representative images of ROS intensity (CellROX in red, and DAPI in blue) after administration of APAP at 0.5, 3, or 10 mM for 7 days in HLOs. Scale bar, 50 μm. Right: Quantification of the number of CellROX-positive events per organoid. n = 15, *P < 0.05. D Albumin secretion after administration of FIAU at 1, 10, or 30 μM for 10 days. n = 3. E Representative images of lipid droplets (Bodipy in green, and DAPI in blue) and mitochondrial depolarization (TMRM in red) in the HLOs after administration of FIAU at 1, 10, or 30 μM for 10 days. Scale bars, 50 μm. Right: Quantification mean of Bodipy fluorescent intensity and quantification of the number of depolarization events per organoid. n = 15, *P < 0.05. F Representative images of lipid droplets (Bodipy in green, and DAPI in blue) and fibrosis (Collagen I in green, and DAPI in blue) in HLOs after administration of MTX at 1, 10, or 30 μM for 7 days. Scale bars, 50 μm. Right: Quantification mean of Bodipy and Collagen fluorescent intensity. n = 15, *P < 0.05. G Expression of fibrogenic marker genes in HLOs after treatment with MTX at 1, 10, or 30 μM for 7 days. n = 3, *P < 0.05. H Albumin secretion after MTX treatment for 7 days in HLOs. n = 3. I Representative images of ROS (CellROX in red, and DAPI in blue), after administration of TAK-875 at 3, 10 or 30 μM for 7 days in HLOs. Scale bars, 50 μm. Right: Quantifications of CellROX-positive events per organoid. n = 15. J Released MCP-1 and IL-6 in HLOs after 7 days of TAK-875 treatment. n = 3. *P < 0.05. K Albumin secretion after TAK-875 treatment for 7 days in HLOs. n = 3. Values represent means with SEM. P values were assessed by one-way ANOVA with Dunnett’s multiple comparisons test (A, B, D, G, H, J, K), Kruskal–Wallis tests (C, E, F, I)