Drug Transport in hiPSC-Derived Proximal Tubule Chips
Organoid-derived proximal tubule epithelia provide bidirectional drug-transport and inhibitor-response measurements for OAT1/3, OCT2/MATE and related transport pathways.
In vitro renal transport, transporter-mediated interactions and nephrotoxicity assessment.
Model & Design
Two kidney organoid-derived Lotus tetragonolobus lectin (LTL)-positive cell preparations, #1-LTL+ and #2-LTL+, compared with immortalized RPTEC/TERT1 proximal tubule cells.
Experimental Format
Porous-membrane chip with separately accessible basal and apical compartments for bidirectional transport measurements.
Model Components
Component
Proximal tubule cells
Description
Two hiPSC-derived kidney organoid preparations and an RPTEC/TERT1 comparator. Different starting hiPSC lines were used for the two differentiation approaches.
Component
Substrates and pharmacological controls
Description
Adefovir, para-aminohippurate, rosuvastatin, metformin and quinidine for transport; probenecid and MK571 for inhibition; cisplatin with or without cimetidine for injury assessment.
Measurements & Endpoints
Bidirectional transport associated with OAT1/3 and OCT2/MATE pathways
Probenecid and MK571 inhibition responses
Cisplatin-associated LDH release and cell viability
Analysis
Compare apparent permeability in basal-to-apical and reverse directions, then calculate the transport ratio. Interpret these measurements alongside transporter localization, barrier properties and injury readouts.
Published Evidence
Study Design
Two organoid-derived chip models compared with an immortalized-cell chip across substrates, inhibitors and injury conditions.
Study Sample
Two differentiation approaches and an immortalized-cell comparator; compound panels varied by experiment. No independent clinical prediction cohort was included.
Comparison
Cell source, transport direction, untreated conditions and matched inhibitor or injury conditions.
Finding
Both organoid-derived models had transport ratios above two for adefovir, para-aminohippurate and rosuvastatin. Cisplatin produced injury signals, with cimetidine effects differing by model and observation time.
Interpretation & Limits
Absolute transport and cell stability differed between preparations, and cell-line and differentiation-protocol effects were not separated.
At 48 hours, #1-LTL+ LDH values no longer differed between conditions; live/dead observations indicated extensive loss of viability by 24 hours.
The high cimetidine concentration and potential PDMS drug sorption require further evaluation.
Two hiPSC-derived proximal tubule models show how transporter localization relates to directional drug transport and inhibitor responses. Transport activity and longer-term cell viability do not necessarily favor the same model.