Inoue Takashi, Ishizaka Yukihito, Sasaki Emi, Lu Jun, Mineshige Takayuki, Yanase Mikio, Sasaki Erika, Shimoda Masayuki
Department of Marmoset Research, Central Institute for Experimental Animals, 3-25-12 Tonomachi, Kawasaki-ku, Kawasaki-shi, Kanagawa 210-0821, Japan.
Department of Intractable Diseases, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan.
Exp Anim. 2018 Jul 30;67(3):321-327. doi: 10.1538/expanim.17-0156. Epub 2018 Mar 22.
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.
普通狨猴（Callithrix jacchus）是一种非人类灵长类动物，因其与人类相似且体型较小，被用于干细胞移植疗法的临床前研究，这使得研究人员无需准备大量细胞即可进行实验。在本研究中，我们为再生医学研究建立了一个狨猴肝纤维化模型。对6只4至6岁的雌性狨猴，每周两次或三次给予剂量为2.5至40 mg/kg的硫代乙酰胺（TAA）。当血液生化指标显示肝脏损伤时，通过肝活检评估肝纤维化情况。给予TAA后，总胆汁酸、天冬氨酸转氨酶和总胆红素升高，血清白蛋白水平降低。连续注射TAA超过11周后，组织学分析在所有动物中均检测到肝纤维化。肝纤维化动物的IV型胶原7S血清水平显著高于正常动物，这可能是狨猴肝纤维化的一个标志物。最后一次给予TAA后进行的系列肝活检显示，诱导的纤维化可持续11周。结果表明，持续给予TAA可诱导普通狨猴出现持续性肝纤维化，并且这个非人类灵长类动物肝纤维化模型有可能评估测试样品改善肝纤维化的治疗效果。
