Exhibitor Tutorial

Axol Bioscience Exhibitor Tutorial: Stem Cell-Derived Human Renal Cells for Compound Screening and Nephrotoxicity Prediction

• DZ

  Dr. Daniele Zink

The kidney is a main target organ for compound-induced toxicity. Recently, we have developed the first pre-validated screening platforms for the accurate prediction of nephrotoxicity in humans (Li et al., Toxicol. Res., 2013; Li et al., Mol. Pharm., 2014; Su et al., BMC Bioinformatics, 2014; Kandasamy et al., Sci. Rep., 2015; Su et al., Arch. Toxicol., 2016; Chuah & Zink, Biotechnol. Adv, 2017; Loo & Zink, Altern. Lab. Anim., 2017). These platforms include the only available predictive methods based on human induced pluripotent stem cell (iPSC)-derived renal cells (Kandasamy et al., 2015; Chuah & Zink, 2017). A protocol has been developed for the rapid generation of iPSC-derived human renal proximal tubular cell (PTC)-like cells. PTC-like cells with a purity of >90% can be obtained within only 8 days of differentiation and these cells can be directly applied for compound screening (Kandasamy et al., 2015). Alternatively, the cells can be cryopreserved. When assays based on iPSC-derived PTC-like cells were combined with machine learning techniques, compound-induced nephrotoxicity could be predicted with a test balanced accuracy of 87% (Kandasamy et al., 2015). In addition, compound-induced injury mechanisms and cellular pathways were correctly identified. PTC-like cells would be also suitable for applications in our recently developed high-throughput platform (Su et al., 2016; Chuah & Zink, 2017). This high-throughput platform predicts nephrotoxicity in humans with a test balanced accuracy of ~80% - 90% depending on the cell type used (Su et al., 2016; Loo & Zink, 2017), and is currently applied in collaboration with the US Environmental Protection Agency to predict the human nephrotoxicity of ToxCast compounds. Currently we are developing kidney-on-chip technologies for repeated dose testing and prediction of the human dose response.