Method Profile
Four species are compared across monolayers, static spheroid-format cultures and perfused microtissues, with biochemical and transcriptomic drug-injury endpoints.
Investigate species-specific drug-induced liver injury (DILI) signals and determine whether perfusion adds value for a defined hepatocyte lot and drug question.
Primary human, cynomolgus-monkey, Wistar-rat and beagle-dog hepatocytes; single human/monkey/dog donors and a pooled rat lot.
Fourteen-day monolayer, static Elplasia and perfused HUMIMIC Chip2 cultures; repeated drug dosing begins on day 6.
Cell preparations
Human lot IIN selected for spheroid formation; monkey VRX, rat JJU and dog JEO. Animal lots were not equivalently spheroid-qualified.
Culture formats
Static monolayers, static microwell aggregates/spheroids and perfused microtissues. Compact spheroids formed consistently in the human preparation, not all species.
Drug panel
Chlorpromazine, bosentan and fialuridine (FIAU) in static concentration-response comparisons; only FIAU at 100 μM in the lower-throughput perfused system.
Normalize biochemical values to initial seeding density or day-matched vehicle as specified for each analysis. Preserve species, time, platform and replicate unit; lower released-enzyme signal can accompany cell loss. Interpret transcriptomic signatures alongside exposure and biochemical results.
Compare species-dependent drug responses across static and perfused formats.
Static drug conditions n = 3; perfused FIAU n = 2. One human/monkey/dog donor and pooled rat lot.
Day-matched vehicle controls and static concentration-response conditions; perfused FIAU at 100 μM only.
Human static cultures gave clearer FIAU responses. Static spheroids showed albumin reduction without significant LDH/AST increases; perfused biochemical trends were nonsignificant. FIAU altered 1,705 genes in human monolayers and 1,724 in static spheroids, with about two-thirds overlapping; the perfused response was attenuated.
Primary hepatocytes from humans, monkeys, rats and dogs were compared in monolayers, static aggregates and perfused microtissues. Static human cultures detected fialuridine responses, while the low-throughput perfused comparison showed weaker, nonsignificant biochemical changes.
