Fig. 4

Generation of the hKORTECs model for drug reabsorption. a Schematic of the hKORTECs model generation from hiPSCs. b Representative morphology of normal and patient-derived hKORTECs. Scale bar, 100 μm. c Schematic of hKORTECs generation from hKOs (top), H&E staining, and immunofluorescence images of renal tubule markers (AQP1, UMOD, AQP2) in KTO models. Scale bar, 100 μm. A schematic illustration was created using Mind the Graph. d Schematic of renal drug transporters (lower left), created using Mind the Graph. mRNA expression of renal influx (OCT2, PEPT1, and PEPT2) and efflux (MRP2, P-gp) transporters in hKTO models. Data are mean ± SEM (n = 6/group). Statistical comparisons were made using a two-tailed unpaired Student’s t-test. **p < 0.01, ns: not significant. e IF of bidirectional markers (ZO-1, P-gp, MRP2, PEPT1, Na+/K+ ATPase, OCT2, OAT3) in hKORTECs. Scale bar, 100 μm. f, g TEER values and basolateral dextran-FITC leakage in normal and patient-hKORTECs. Mean ± SEM (n = 4 per group); unpaired two-tailed t-test. **p < 0.01. h IF of endocytic receptor megalin in hKORTECs. Scale bar, 100 μm. Mean ± SEM (n = 6/group); unpaired two-tailed t-test. *p < 0.05. i Functional analysis of megalin-mediated albumin trafficking in hKORTECs. Mean ± SEM (n = 5/group); unpaired two-tailed t-test. **p < 0.01. j Summary of transepithelial transport and MRP2/4-mediated apical efflux in normal and patient-hKORTECs (top), and apical CDF fluorescence with/without MK571. Data are mean ± SEM (n = 5/group). Statistical analysis was made using two-way ANOVA with Tukey’s test. k Summary and cytotoxicity assessment following cisplatin and cimetidine treatment via drug transporter modulation. Data are mean ± SEM (n = 5/group); two-way ANOVA with Tukey’s test. *P < 0.05 is considered significant. ns: not significant. Schematic illustrations included in (i–k) were created using Mind the Graph