Characterization of Corning® HepatoCells for Drug Uptake Transport Assays

Abstract

Increasing evidence shows that drug transporters play an important role in drug‐induced hepatotoxicity and adverse drug‐drug interactions. Regulatory agencies (USFDA and EMA) recommend in their drug interaction guidelines to investigate clinically relevant transporters for new molecular entities. Here we report characterization of Corning HepatoCells (derived from primary human hepatocytes) for uptake transporter study, specifically OCT1, OATP1B1/1B3, and NTCP. When cultured on Corning BioCoat™ Collagen I coated tissue culture plates for 3‐4 days, Corning HepatoCells demonstrated time‐dependent and concentration‐dependent uptake of prototypical substrates of OCT1, OATP1B1/1B3, and NTCP, with Km values comparable to literature data. Multiple lots of Corning HepatoCells generated similar kinetic profiles. Inhibition assays were also performed and the results showed concentration dependent inhibition with similar profiles among multiple lots of cells, and IC50 values were in line with literature data from other test systems. In addition to active expression of uptake transporters, Corning HepatoCells also demonstrated bile canaliculi formation suggesting active expression of efflux transporters. In conclusion, the study demonstrated that Corning HepatoCells actively express functional uptake transporters, and this model represents a renewable source of human hepatic cells with consistent performance for uptake transporter study.