In both preclinical and clinical testing, drug induced liver injury (DILI) is the major cause of drug attrition, costing pharmaceutical companies millions of dollars every year. It is therefore essential to rapidly identify and remove drug candidates that pose a risk, decreasing development costs and improving post market success. Currently primary human hepatocytes are the most widely used cell type for the prediction of DILI. However when cultured in vitro they do not proliferate and rapidly lose their phenotype, in particular drug metabolism. Furthermore, sources are limited and usually isolated from diseased tissue, limiting their utility. The cost effective delivery of human tissue from a renewable resource, such as pluripotent stem cells, offers a solution to the issues associated with human somatic cells for in vitro testing. Of note, stem cell derived hepatocytes have been shown to be as sensitive and as human hepatocytes (Szkolnicka et al 2014, Stem Cells Translational Medicine and Szkolnicka et al 2016, Stem Cells Translational Medicine). More recently, improvements in culture methods and protocols have led to automation of these processes, leading to further improvements in hepatocyte function and stability. We are currently using those models to better understand fetal liver exposure to environmental toxins and the role of the innate immune system during virus infection of the liver. Going forward our automated systems will be perfused, multiplexed and combined with a bank cell lines to study genetic variation in the human population. These data will be composed of standard biochemical and label free real time monitoring measurements, generating multiparametric datasets of significant value for industry and ultimately the patient.

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