The team at Radboud University Medical Centre developed the NephroScreen containing polarized human proximal tubule cells in a multicompartmental microfluidic titerplate, as a better predictive in vitro system for drug-induced kidney toxicity (DIKI). During Phase 1, they demonstrated that culturing the stable human renal cell line ciPTEC in a microfluidic microtiter plate (OrganoPlate®) provides robust renal toxicity testing. The ciPTEC, cultured under perfused conditions, are accessed from both apical and basal sides. Each plate contains 96 tubules for individual analysis in situ and sampling for high-throughput screening of DIKI. The intact function of renal transporters and metabolic enzymes combined with specific responses to nephrotoxicants demonstrated the toxicological relevance of our system. NephroScreen allowed detection of toxicity markers, renal transport function and leakage markers. High reproducibility in two independent labs demonstrated robustness of the system. CiPTECs viability over prolonged (≥ 3 weeks) periods of time was demonstrated.
During Phase 2, the NephroScreen will be validated against current in vitro benchmarks and known clinical data. The team will demonstrate reproducibility with a range of biomarkers and cell functionalities.
NephroScreen is transferred to the Sponsors for implementation in their screening setups.
Ultimately, the NephroScreen will be commercialised as an in vitro renal toxicity screenings tool to answer the ambition to provide a better alternative to animal studies both in terms of throughput, costs and predictability.
Full details about this CRACK IT Challenge can be found on the CRACK IT website.
Contractor(s)Dr Martjin Wilmer
Radboud University Medical Centre
University of Applied Sciences and Arts Northwestern Switzerland