Development of human growth hormone-treated chimeric mice with humanized livers for an evaluation model of drug-induced fatty liver disease.

Chimeric mice with humanized livers were used to evaluate drug-induced liver injury (DILI). However, lipid accumulation is observed in the human hepatocytes of chimeric mice because of human growth hormone deficiency (GHD), which is an obstacle in the evaluation of drug-induced fatty liver disease (DIFLD), a common type of DILI. Previously, we showed that lipid droplets were reduced by the administration of human growth hormone (h-GH) to chimeric mice.

Humanized liver mouse model with transplanted human hepatocytes from patients with ornithine transcarbamylase deficiency.

Ornithine transcarbamylase deficiency (OTCD) is a metabolic and genetic disease caused by dysfunction of the hepatocytic urea cycle. To develop new drugs or therapies for OTCD, it is ideal to use models that are more closely related to human metabolism and pathology. Primary human hepatocytes (HHs) isolated from two patients (a 6-month-old boy and a 5-year-old girl) and a healthy donor were transplanted into host mice (hemi-, hetero-OTCD mice, and control mice, respectively).

Detection of acute toxicity of aflatoxin B1 to human hepatocytes in vitro and in vivo using chimeric mice with humanized livers.

Aflatoxin B1 (AFB1), a mycotoxin, is acutely hepatotoxic to many animals including humans. However, there are marked interspecies differences in sensitivity to AFB1-induced toxicity depending on bioactivation by cytochrome P450s (CYPs). In the present study, we examined the applicability of chimeric mice with humanized livers and derived fresh human hepatocytes for in vivo and vitro studies on AFB1 cytotoxicity to human hepatocytes.