Alternative methods for the efficient and accurate prediction of organ-specific toxicity
Alternatives to animal testing are of increasing importance in toxicology. This development is driven by various causes, including concerns about the predictivity of animal models. Also, animal models are too slow and costly for screening of the large and increasing numbers of compounds that need to be tested. Furthermore, changes in legislation (e.g. animal bans for cosmetics testing) and other developments steeply increase the demand for alternative methods. However, many alternative methods are of unknown predictivity, and accepted alternative methods for predicting toxicity for human internal organs are not available. This problem is addressed by our work, which was initially focused on the kidney (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). Our kidney-specific methods include the only available predictive methods based on human induced pluripotent stem cell-derived renal cells and a predictive high-throughput platform. The high-throughput platform is currently applied in collaboration with the US Environmental Protection Agency to predict the human nephrotoxicity of ToxCast compounds. Based on a similar methodology we are now developing high-throughput platforms for predicting toxicity for other human organ systems, including liver and vasculature, and we are also establishing predictive organ-on-chip technologies for efficient repeated dose testing.
Faezah Hussain1, Jacqueline K. C. Chuah1, Lit-Hsin Loo2 and Jackie Y. Ying1 and Daniele Zink1
1Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore 138669, Singapore
2Bioinformatics Institute, 30 Biopolis Street, #07-01 Matrix, Singapore 138671, Singapore