Transcriptional comparisons of stem cell-derived hepatocytes (hiPS-Hep), HepaRG cells and 3D human hepatocyte spheroids as predictive in vitro systems for drug-induced liver injury

Three current hepatic in vitro cell systems were compared at the gene expression level in order to determine their suitability for investigations of hepatotoxicity. For mechanistic investigations we focussed on the PHH spheroid system, treating them with IC10 concentrations of either aflatoxin B1, amiodarone or chlorpromazine for up to 2 weeks and investigating the transcriptional changes induced by each of the compounds. We observed significant alterations in genes regulating carcinogenic, steatotic and cholestatic pathologies respectively. At 48h, 7 days (3 treatments) and 14 days (6 treatments) cells were harvested and RNA isolated. For each treatment three technical replicates were analysed.