Thioacetamide-induced hepatic fibrosis in the common marmoset

被引:15
|
作者
Inoue, Takashi [1 ]
Ishizaka, Yukihito [2 ]
Sasaki, Emi [1 ]
Lu, Jun [2 ]
Mineshige, Takayuki [1 ]
Yanase, Mikio [3 ]
Sasaki, Erika [1 ,4 ]
Shimoda, Masayuki [5 ]
机构
[1] Cent Inst Expt Anim, Dept Marmoset Res, Kawasaki Ku, 3-25-12 Tonomachi, Kawasaki, Kanagawa 2100821, Japan
[2] Natl Ctr Global Hlth & Med, Dept Intractable Dis, Shinjuku Ku, 1-21-1 Toyama, Tokyo 1628655, Japan
[3] Natl Ctr Global Hlth & Med, Dept Gastroenterol, Shinjuku Ku, 1-21-1 Toyama, Tokyo 1628655, Japan
[4] Keio Univ, Keio Adv Res Ctr, Shinjuku Ku, 35 Shinanomachi, Tokyo 1608582, Japan
[5] Natl Ctr Global Hlth & Med, Diabet Res Ctr, Islet Cell Transplantat Project, Shinjuku Ku, 1-21-1 Toyama, Tokyo 1628655, Japan
关键词
liver fibrosis; marmoset; nonhuman primate; thioacetamide; COLLAGEN 7S DOMAIN; LIVER FIBROSIS; IV COLLAGEN; CELL THERAPY; STEM-CELL; DISEASE; SERUM; TRANSPLANTATION; MODELS;
D O I
10.1538/expanim.17-0156
中图分类号
S85 [动物医学(兽医学)];
学科分类号
0906 ;
摘要
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.
引用
收藏
页码:321 / 327
页数:7
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