Suppression of Carbon Tetrachloride-Induced Liver Fibrosis by Transplantation of a Clonal Mesenchymal Stem Cell Line Derived From Rat Bone Marrow
Suppression of Carbon Tetrachloride-Induced Liver Fibrosis by Transplantation of a Clonal Mesenchymal Stem Cell Line Derived From Rat Bone Marrow
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DOI：
10.3727/096368909788237140
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发表时间：
2009-01-01
影响因子：
3.3
通讯作者：
Huh, Narn-ho
中科院分区：
文献类型：
--
作者：
Hardjo, Marhaen;Miyazaki, Masahiro;Huh, Narn-ho
肝细胞或骨髓来源的细胞移植已被证明可以改善动物模型中的肝纤维化，但没有直接比较相对效率。本研究旨在比较LIS法建立的骨髓间充质干细胞克隆系（rBM 25/S3）及其向脂肪细胞或肝细胞分化的衍生物对大鼠肝纤维化的抑制作用。在培养中诱导rBM 25/S3细胞分化为成脂细胞或成肝细胞后，我们在开始四氯化碳处理（1 ml/kg体重，每周两次，共8周）之前和4周后将这三种类型的细胞脾内移植到大鼠中（3 × 10（7）个细胞/大鼠）以诱导肝纤维化。未分化的rBM 25/S3细胞对肝纤维化的抑制作用最强，其次是成脂细胞和肝细胞。MMP-2和MMP-9在未分化的rBM 25/S3细胞中的表达水平也最高。这些结果表明，骨髓来源的克隆间充质干细胞系是有用的细胞介导的抑制肝纤维化的进一步机制的研究，这样的细胞系将提供适当的细胞来源的肝硬化移植治疗的信息。
Transplantation of hepatocytes or bone marrow-derived cells has been shown to ameliorate liver fibrosis in animal models, but no direct comparison of relative efficiency has been made. The aim of this study was to compare the efficiency of a bone marrow-derived clonal mesenchymal stem cell line established by LIS (rBM25/S3) with that of its adipogenic or hepatogenic differentiation derivative for Suppression of rat liver fibrosis. After induction of differentiation of rBM25/S3 cells into adipogenic or hepatogenic cells in Culture, we intrasplenically transplanted the three types of cells into rats (3 x 10(7) cells/rat) before and 4 weeks after initiation of carbon tetrachloride treatment (1 ml/kg body weight twice a week for 8 weeks) to induce liver fibrosis. Undifferentiated rBM25/S3 cells were the most effective for suppression of liver fibrosis, followed by the adipogenic cells and hepatogenic cells. Expression levels of MMP-2 and MMP-9 were also highest in undifferentiated rBM25/S3 cells. These results indicate that bone marrow-derived clonal mesenchymal stem cell lines are useful for further mechanistic studies on cell-mediated suppression of liver fibrosis and that such cell lines will provide information on an appropriate cell source for transplantation therapy for cirrhosis.