# Advanced Kidney Models In Vitro Using the Established Cell Line Renal Proximal Tubular Epithelial/Telomerase Reverse Transcriptase1 for Nephrotoxicity Assays

## TL;DR

This study develops advanced in vitro kidney models using a specific cell line to better predict drug-induced nephrotoxicity.

## Contribution

The novelty lies in creating 2.5D and kidney-on-a-chip models using RPTEC/TERT1 cells to mimic renal proximal tubule function.

## Key findings

- The 2.5D model forms tubular structures without hydrogels, resembling native kidney architecture.
- The kidney-on-a-chip model applies shear stress, enhancing physiological relevance.
- The models responded to nephrotoxic compounds like cisplatin, tacrolimus, and daunorubicin.

## Abstract

Nephrotoxicity stands as one of the most limiting effects in the development and validation of new drugs. The kidney, among the organs evaluated in toxicity assessments, has a higher susceptibility, with nephrotoxic potential frequently evading detection until late in clinical trials. Traditional cell culture, which has been widely used for decades, does not recapitulate the structure and complexity of the native tissue, which can affect cell function, and the response to cytotoxins does not resemble what occurs in the kidney. In the current study, we aimed to address these challenges by creating in vitro kidney models that faithfully biomimic the dynamics of the renal proximal tubule, using the well-established RPTEC/TERT1 cell line. For doing so, two models were developed, one recreating tubule-like structures (2.5D model) and the other using microfluidic technology (kidney-on-a-chip). The 2.5D model allowed tubular structures to be generated in the absence of hydrogels, and the kidney-on-a-chip model allowed shear stress to be applied to the cell culture, which is a physiological stimulus in the renal tissue. After characterization of both models, different nephrotoxic compounds such as cisplatin, tacrolimus, and daunorubicin were used to study cell responses after treatment. The developed models in our study could be a valuable tool for pre-clinical nephrotoxic testing of drugs and new compounds.