Contribution and Mobilization of Mesenchymal Stem Cells in a mouse model of carbon tetrachloride-induced liver fibrosis.
Contribution and Mobilization of Mesenchymal Stem Cells in a mouse model of carbon tetrachloride-induced liver fibrosis.
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间充质干细胞在四氯化碳诱导的肝纤维化小鼠模型中的贡献和动员
DOI：
10.1038/srep17762
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发表时间：
2015-12-08
影响因子：
4.6
通讯作者：
Wei L
中科院分区：
文献类型：
--
作者：
Liu Y;Yang X;Jing Y;Zhang S;Zong C;Jiang J;Sun K;Li R;Gao L;Zhao X;Wu D;Shi Y;Han Z;Wei L
肝纤维化与骨髓间充质干细胞(BM-MSCs)有关。在这项研究中，我们的目标是确定MSCs在这一过程中扮演什么角色，以及它们如何从骨髓中动员。我们采用了四氯化碳(CCl4)诱导的小鼠肝纤维化模型。冰冻切片检测小鼠和人肝纤维化组织中MSCs的数量。检测丙氨酸氨基转移酶(ALT)和天冬氨酸氨基转移酶(AST)以评估肝功能。研究发现，外源性和内源性的MSCs均可加重肝纤维化，减轻肝损伤，表现为血清ALT和AST水平降低。基质细胞衍生因子-1(SDF-1)α/CXCR4是调控骨髓间充质干细胞向肝纤维化迁移的最重要的趋化轴。冰冻切片结果显示，这种迁移并非始于肝损伤开始，而是在肝与骨髓之间的SDF-1α表达平衡被破坏时发生的，且肝脏中SDF-1α的表达高于骨髓。我们的研究结果进一步证明了BM-MSCs在肝纤维化中的作用，并阐明了在CCl4诱导的早期肝纤维化小鼠模型中MSCs动员的机制。
Hepatic fibrosis is associated with bone marrow derived mesenchymal stem cells (BM-MSCs). In this study, we aimed to determine what role MSCs play in the process and how they mobilize from bone marrow (BM). We employed a mouse model of carbon tetrachloride(CCl4)-induced liver fibrosis. Frozen section was used to detect MSCs recruited to mice and human fibrotic liver. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) was detected to assess liver function. It was found that MSCs of both exogenous and endogenous origin could aggravate liver fibrosis and attenuate liver damage as indicated by lower serum ALT and AST levels. Stromal cell–derived factor-1 (SDF-1α)/ CXCR4 was the most important chemotactic axis regulating MSCs migration from BM to fibrotic liver. Frozen section results showed that the migration did not start from the beginning of liver injury but occured when the expression balance of SDF-1α between liver and BM was disrupted, where SDF-1α expression in liver was higher than that in BM. Our findings provide further evidence to show the role of BM-MSCs in liver fibrosis and to elucidate the mechanism underlying MSCs mobilization in our early liver fibrosis mice model induced by CCl4.