AN EXPERIMENTAL-MODEL OF ACUTE LIVER-INJURY USING MULTICELLULAR SPHEROIDS COMPOSED OF RAT PARENCHYMAL AND NONPARENCHYMAL LIVER-CELLS

Massive hepatic cell necrosis can be induced by Corynebacterium parvum and lipopolysaccharide (LPS) in rats. In this model, serum LDH, GOT a nd GPT activities are significantly increased in vivo within several h ours after LPS injection. An in vitro experimental acute liver injury animal model was produced by using multicellular spheroids composed of rat parenchymal and non-parenchymal liver cells. These multicellular spheroids were prepared by detaching the confluent monolayer on the co llagen-conjugated thermo-responsive polymer coated culture dish at a t emperature below the lower critical solution temperature and culturing it on the non-adhesive substratum. LPS caused clear elevations of GOT , GPT and LDH activities from these spheroids into the medium. However , the increase of LDH activity was only observed in the monolayer cult ure system. These results suggest that the multicellular spheroids of liver cells are useful models as an alternative to animal tests for he patotoxicity.