Abstract

Introduction: Drug-induced liver injury (DILI) continues to be a major source of clinical attrition, precautionary warnings, and post-market withdrawal of drugs. We have developed a 3D primary human hepatocyte spheroid assay to study DILI with the goal to provide a more predictive hepatotoxicity model over our 2D cell line model. We used various imaging systems to support assay development and optimisation.

Results: Imaging endpoints enabled the detection of spheroid formation for assay QC, essential for chronic assay formats. Spheroid number, shape, size, intensity and amount of debris was also quantified using Columbus™ image analysis software. Our studies demonstrated improved sensitivity over existing 2D assay formats.

Conclusion: This phenotypic and human relevant assay leads to greater confidence in the assessment of potential pre-candidate’s selection for drug discovery projects across GSK.