Human Menstrual Blood-Derived Stem Cells Ameliorate Liver Fibrosis in Mice by Targeting Hepatic Stellate Cells via Paracrine Mediators.
Human Menstrual Blood-Derived Stem Cells Ameliorate Liver Fibrosis in Mice by Targeting Hepatic Stellate Cells via Paracrine Mediators.
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DOI：
10.5966/sctm.2015-0265
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发表时间：
2017-01
影响因子：
6
通讯作者：
Xiang C
中科院分区：
文献类型：
--
作者：
Chen L;Zhang C;Chen L;Wang X;Xiang B;Wu X;Guo Y;Mou X;Yuan L;Chen B;Wang J;Xiang C
间充质干细胞（MSC）可能在治疗慢性肝病（CLD）的再生医学中具有潜在的应用。人类经血是 MSC 的新来源，称为经血衍生干细胞 (MenSC)。与骨髓间充质干细胞相比，MenSCs具有更高的增殖率，并且可以通过简单、安全、无痛的程序获得，无需考虑伦理问题。尽管 MenSCs 在某些疾病中的治疗功效已被探索，但其对肝纤维化的影响仍不清楚。在本研究中，我们研究了 MenSC 移植对四氯化碳诱导的小鼠肝纤维化模型的治疗效果。这些结果表明，MenSC 在移植后长达 2 周内显着改善了肝功能，减少了胶原蛋白沉积，并抑制了活化的肝星状细胞。此外，对表达绿色荧光蛋白的 MenSC 的追踪表明，移植的细胞迁移到损伤部位，但很少分化为功能性肝细胞样细胞。 Transwell 共培养实验还表明，MenSC 通过分泌单核细胞趋化蛋白-1、白细胞介素-6、肝细胞生长因子、生长相关癌基因、白细胞介素-8 和骨保护素来抑制 LX-2 细胞（永生化肝星状细胞系）的增殖。总的来说，我们的结果为 MenSCs 在肝纤维化中的抗纤维化能力提供了初步证据，并表明这些细胞可能是治疗 CLD 的替代治疗方法。干细胞转化医学 2017 年；6：272–284
Mesenchymal stem cells (MSCs) may have potential applications in regenerative medicine for the treatment of chronic liver diseases (CLDs). Human menstrual blood is a novel source of MSCs, termed menstrual blood‐derived stem cells (MenSCs). Compared with bone marrow MSCs, MenSCs exhibit a higher proliferation rate and they can be obtained through a simple, safe, painless procedure without ethical concerns. Although the therapeutic efficacy of MenSCs has been explored in some diseases, their effects on liver fibrosis are still unclear. In the present study, we investigated the therapeutic effects of MenSC transplantation in a carbon tetrachloride‐induced mouse model of liver fibrosis. These results revealed that MenSCs markedly improved liver function, attenuated collagen deposition, and inhibited activated hepatic stellate cells up to 2 weeks after transplantation. Moreover, tracking of green fluorescent protein‐expressing MenSCs demonstrated that transplanted cells migrated to the sites of injury, but few differentiated into functional hepatocyte‐like cells. Transwell coculturing experiments also showed that MenSCs suppressed proliferation of LX‐2 cells (an immortalized hepatic stellate cell line) through secretion of monocyte chemoattractant protein‐1, interleukin‐6, hepatocyte growth factor, growth‐related oncogene, interleukin‐8, and osteoprotegerin. Collectively, our results provided preliminary evidence for the antifibrotic capacity of MenSCs in liver fibrosis and suggested that these cells may be an alternative therapeutic approach for the treatment of CLDs. Stem Cells Translational Medicine 2017;6:272–284