Thioacetamide-induced hepatic fibrosis in the common marmoset.

The common marmoset (Callithrix jacchus) is a nonhuman primate that is used for preclinical research on stem cell transplantation therapies due to its similarity to human beings as well as its small size, enabling researchers to perform experiments without preparing a large number of cells. In this study, we developed a marmoset hepatic fibrosis model for regenerative medicine research. Six female marmosets aged 4-6 years were administered thioacetamide (TAA) at a dose of 2.5-40 mg/kg two or three times a week. Hepatic fibrosis was assessed by liver biopsy when blood chemistry indicated liver damage. Administration of TAA increased total bile acid, aspartate aminotransferase, and total bilirubin and decreased serum albumin levels. Following more than 11 weeks of continuous injection of TAA, histological analyses detected hepatic fibrosis in all animals. Type IV collagen 7S serum levels in animals with hepatic fibrosis were significantly higher than in normal animals as a possible marker of hepatic fibrosis in marmosets. Serial liver biopsies following the last administration of TAA revealed that induced fibrosis remained up to 11 weeks. The results suggest that continuous TAA administration induces persistent hepatic fibrosis in the common marmoset and this nonhuman primate hepatic fibrosis model have the possibility to evaluate the therapeutic effects of test samples to ameliorate hepatic fibrosis.

Japanese herbal medicine TJ-48 prevents autoimmune diabetes in NOD mice.

Type 1 diabetes mellitus (T1DM) is mainly caused by CD8(+) cytotoxic T cell infiltration into islets. Recently, the role of regulatory T cells (Tregs) in the prevention of the onset of T1DM was reported. We reported that TJ-48, a common Japanese herbal medicine, decreased Treg population in cancer patients, thus we investigated whether TJ-48 had an influence on T1DM onset using NOD mice. In the TJ-48 group, TJ-48 (2.0g/kg/day) was administered in the drinking water for NOD mice from three weeks of age to 20 weeks of age. Their body weight and fast blood glucose (FBG) were measured every week. Histology (Hematoxylin-Eosin staining) was investigated every month. Lymphocyte profiles were investigated every month with FACS. The results were compared to the age-matched NOD mice control group. FBG of the control group mice showed diabetic status of 66.7% at 18 weeks of age. On the other hand, the TJ-48 group mice showed diabetic status of 16.7% at 18 weeks of age (p = 1.905E-06). There were no significant differences in general conditions or body weight between the two groups. Lymphocyte infiltrations into islets were dramatically suppressed in the TJ-48 group. The effect of TJ-48 on decreasing Tregs was less apparent in the NOD mice model. TJ-48 inhibited lymphocyte infiltrations into islets, which led to preventing the onset of T1DM in NOD mice.