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Cancer Research Institute, Biomedical Research Center, Slovak Academy of  Sciences, Bratislava, Slovakia

Renal advanced in vitro models for nephrotoxicity determination  

The natural renal function, to serve as a primary organ for detoxification and  elimination of xenobiotics, make the kidneys especially susceptible to toxic chemicals  including drugs. Hence, the development of sensitive predictive models and high  throughput cell-based in vitro assays for evaluation of the nephrotoxic potential of  toxicants as well as new therapeutic substances is an urgent need and a major  challenge.  

Microfluidic technology offers an alternative platform for in vitro nephrotoxicity  screening of chemicals including nanomaterials under physiologically-relevant  conditions and provides an attractive strategy for enhancing the efficiency of hazard  profiling. In this study, a new microfluidic module with a size of a microscopic slide  and a microcavity with a membrane made from silicon nitride (Si3N4) integrated into a  fluidic system with tubing, valves, and pump delivering cell culture medium to the  cells under a constant medium flow rate was investigated. The human renal proximal  tubule epithelial TH-1 cells were cultivated under standard conditions (on inserts,  static conditions) and on the chip-based microfluidic module. The aim of this work  was to verify the suitability of the microhole chip and the microfluidic module for the  cultivation of TH-1 cells as a basis for the development of the kidney-on-a-chip  model. TH-1 cells were exposed to cisplatin, a known nephrotoxic compound, and  fluorescent-labeled silica nanoparticles (FITC-SiO2NPs). The cytotoxic effects of  xenobiotics were evaluated by vital staining using fluorescein diacetate and  propidium iodide and by the transendothelial electrical resistance (TEER)  measurement. We observed no changes in cell morphology and proliferation activity  in TH-1 cells growing on the microchip in comparison with the inserts. Moreover, the  microfluidic module allowed a continuous optical characterization and TEER  measurement of the cells during cultivation and exposure, thus offering a promising  tool for screening of xenobiotics. The human renal proximal tubule epithelial TH1  cells are promising in vitro kidney model for the development of a kidney-on-a-chip  module mimicking more realistic human exposure to toxicants. 


The research leading these results has received funding from grant H2020 HISENTS  (GA no. 685817) and VISION (GA no. 857381). Kristina Kopecka received STSM  Grant (ID 42926) under COST Action CA 17140 "Cancer Nanomedicine from the  Bench to the Bedside" supported by COST (European Cooperation in Science and  Technology).