Renal proximal tubule cell (PTC) monolayer is a unique in vitro approach for investigating renal drug handling, identifying drug-transporter interactions, potential nephrotoxicity and transporter mediated drug-drug interactions. SOLVO offers tailored services in partnership with Newcells Biotech Ltd.. Primary renal proximal tubule cell (PTC) monolayer model maintains the full complement and expression level of endogenous renal transporters, resulting in a more physiologically relevant, and therefore predictive, model of drug handling and nephrotoxicity in the clinical setting.
- Kidney PTC are isolated from fresh normal kidney, less than 12 hours ex vivo.
- Cells are grown on permeable filter HTS Transwell membranes to generate fully functional differentiated monolayers with TEER of ~140-180 Ω.cm ².
- Human PTCs express a full range of key renal transporters (confirmed by qPCR, immunochemistry, or functional assay):
- Transporters expressed at the apical membrane: - MDR1, MRP2, MRP4, MRP1, BCRP, MATE, OAT4, OCTN1, OCTN2, NaPi2a
- Transporters expressed at the Basolateral membrane: - OAT1, OAT2, OAT3, OCT2, OCT3, OATP4C1, NBC.
- Transporter function has been validated using a wide range of drug molecules with diverse in vivo renal clearance values.
The following services can be performed in partnership with Newcells Biotech Ltd.:
- Flux measurement, including determination of paracellular contribution to total flux.
- Net transport measurements. • Measurement of intracellular drug and metabolite concentrations.
- Mechanistic understanding of the role and importance of individual transporters to the renal clearance pathway.
- Identification of potential transporter-mediated drug-drug interactions.
- Investigation of nephrotoxic potential using a panel of early damage biomarkers.