Objective

The disposition and clearance of drugs by the kidney relies largely on a subset of membrane transport pumps known as solute carrier proteins (SLC). Among the SLC families, OAT1(SLC22A6), OCT2(SLC22A2) and OAT3(SLC22A8) are the most important transporters in kidney tissue, often acting as the limiting factor for solute clearance. Thus, there is a requirement for an in vitro model with human kidney origination, accurate clinical predictability and consistent data output. Unfortunately, primary RPTEC cells lose OAT1, OCT2 and OAT3 transporter expression in culture. Transiently expressing these transporters in primary RPTEC cells also shows large variations between lots. In our study, we have generated transporter cell models using well characterized hTERT-immortalized RPTECs that stably overexpress the OAT1, OCT2 or OAT3 gene. Clones show typical epithelial morphology and correct marker expression. Most importantly, we verified that the overexpressed transporters have normal transport activities, and the uptake can be inhibited by well know inhibitors in a dose dependent manner. Overall, our data has shown that these modified cell lines are useful tools which provide human kidney tissue related results, improved consistency over time, and have more predictability for clinical trials versus current models for in vitro testing.