Method Profile
Lipid, function, expression and two CYP metabolite assays compare donor suspensions with three fatty-acid-induced human hepatic systems.
Choose hepatic models and sampling times for drug-metabolism and ADME studies under steatotic conditions.
PHH suspensions, sandwiches and spheroids, plus HepaRG/LX-2/HUVEC micro-organoids. Suspensions compare donor groups; the other systems compare fatty-acid exposure with their own controls.
Day-0 suspension, day-7 sandwich and day-10 spheroid/micro-organoid sampling. Induced systems use 600 µM oleic/palmitic acid at 2:1, with different carriers and media; micro-organoids use a matched methanol vehicle control.
Human hepatic systems
Sandwiches and spheroids use three PHH donor lots; micro-organoids combine HepaRG, LX-2 and HUVECs at 4:2:1.
Functional and molecular measurements
Lipid staining, albumin/LDH/viability, a 33-gene panel and LC–MS/MS metabolites for CYP1A2 and CYP2C9.
Use within-platform controls and separate donor, independent-run and technical-replicate units. Donor comparisons are distinct from induced steatosis, and architecture alone does not explain cross-platform differences.
Phenotypic, expression and functional CYP comparisons across four hepatic systems.
Three PHH donor lots for sandwiches and spheroids; the suspension arm used six donors per group. Replicates differ by endpoint.
Putatively healthy versus putative MASH donors in suspensions; untreated controls for each induced system.
Fatty-acid-related CYP changes depended on model and donor; neither CYP activity changed significantly in micro-organoids.
A four-platform comparison combined lipid imaging, liver-function measurements, expression profiling and CYP assays. Lipid accumulation did not uniformly reduce drug metabolism, and differences depended on the model and donor.
