Transplantation of bone marrow cells reduces CCl4-induced liver fibrosis in mice
Transplantation of bone marrow cells reduces CCl4-induced liver fibrosis in mice
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DOI：
10.1111/j.1478-3231.2010.02364.x
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发表时间：
2011-08-01
影响因子：
6.7
通讯作者：
Ryu, Kyung-Ha
中科院分区：
文献类型：
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作者：
Cho, Kyung-Ah;Lim, Goh-Woon;Ryu, Kyung-Ha
背景：我们研究了注射CCl4诱导的肝纤维化的可逆性以及干细胞在逆转肝损伤中的作用。此外，还分析了修复过程中骨髓细胞中最有效的细胞比例。方法：C57BL/6小鼠注射CCl4 5周后随机分为4组：对照组、GFP供体骨髓移植后5周、10周和5周后处死小鼠。比较两组间的肝功能测试和肝纤维化标志物的实时聚合酶链式反应(PCR)。为确定修复肝损伤最有效的BMC组分，将小鼠分为3组：单纯粒细胞集落刺激因子(G-CSF)组、单核细胞(MNC)移植组和Lin-SCA-1+c-kit+造血干细胞(HSC)移植组。移植后8天取材，进行形态计量学、免疫组织化学分析，比较细胞外基质和肝纤维化相关因子的表达。结果：CCl4诱导的小鼠肝纤维化不能自发恢复，但可持续至10周，但注射BMCs组肝纤维化程度减轻，肝功能改善。G-CSF动员促进了损伤肝脏的恢复，以单核细胞组分和Lin-SCA-1+c-kit+HSC组分的动员效果最好，两组间差异无统计学意义。结论：骨髓间充质干细胞移植联合G-CSF动员能有效治疗小鼠肝损伤。对于患有肝纤维化的人类，这些都是很有希望的自体移植技术。
Background: We investigated the reversibility of liver fibrosis induced with a CCl4 injection and the role of stem cells in reversing the hepatic injury. Furthermore, the most effective cell fraction among bone marrow cells (BMCs) in the repair process was analysed. Methods: C57BL/6 mice were divided into four groups after 5 weeks of injection of CCl4: control, sacrificed after 5 weeks, sacrificed at 10 weeks and sacrificed 5 weeks later after GFP-donor BM transplantation. Liver function tests and real-time polymerase chain reaction (PCR) of markers indicating liver fibrosis were compared between the groups. To identify the most effective BMC fraction that repairs liver injury, the mice were divided into three groups after the injection of CCl4 for 2 days: granulocyte colony stimulating factor (G-CSF) only, mononuclear cell (MNC) transplantation and Lin-Sca-1+c-kit+haematopoietic stem cell (HSC) transplantation. Eight days after transplantation, the mice were harvested and morphometric, immunohistochemical analyses were performed to compare the expression of extracellular matrix and liver fibrosis-related factors. Results: The liver fibrosis induced by CCl4 was not spontaneously recovered but was persistent until 10 weeks, but the group injected with BMCs had less fibrosis and better liver function. Mobilization with G-CSF increased the recovery of the injured liver and the best results were seen in those mice administered the MNC fraction and Lin-Sca-1+c-kit+HSC fraction, with no difference between the two groups. Conclusion: BMC transplantation and stem cell mobilization with G-CSF effectively treats liver injury in mice. These are promising techniques for autologous transplantation in humans with liver fibrosis.