The application of omics-based human liver platforms for investigating the mechanism of drug-induced hepatotoxicity in vitro

作者: Jian Jiang , Charlie D. Pieterman , Gökhan Ertaylan , Ralf L. M. Peeters , Theo M. C. M. de Kok

DOI: 10.1007/S00204-019-02585-5

关键词: ToxicogenomicsComputational biologyAnimal testingComputer scienceInduced pluripotent stem cellDrug developmentOmicsPharmaceutical industryMechanism (biology)In vitro

摘要: Drug-induced liver injury (DILI) complicates safety assessment for new drugs and poses major threats to both patient health drug development in the pharmaceutical industry. A number of human cell-based vitro models combined with toxicogenomics methods have been developed as an alternative animal testing studying DILI mechanisms. In this review, we discuss systems their applications omics-based drug-induced hepatotoxicity studies. We furthermore present bioinformatic approaches that are useful analyzing toxicogenomic data generated from these current potential contributions understanding mechanisms DILI. Human pluripotent stem cells, carrying donor-specific genetic information, hold great advancing study individual-specific toxicological responses. When co-cultured other liver-derived non-parenchymal cells a microfluidic device, resulting dynamic platform enables us immune-mediated hypersensitivity accelerates personalized toxicology flexible would also support assembly more advanced organs-on-a-chip further bridging gap between vivo conditions. The standard transcriptomic analysis cell can be complemented causality-inferring improve These involve statistical techniques capable elucidating regulatory interactions parts use elaborated models, harmony will pave way establishing powerful methodology systematically assess across wide range

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