Umbilical cord-derived mesenchymal stem cells alleviate liver fibrosis in rats
Umbilical cord-derived mesenchymal stem cells alleviate liver fibrosis in rats
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DOI：
10.3748/wjg.v22.i26.6036
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发表时间：
2016-07-14
影响因子：
4.3
通讯作者：
Linghu, En-Qiang
中科院分区：
文献类型：
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作者：
Chai, Ning-Li;Zhang, Xiao-Bin;Linghu, En-Qiang
目的：评价脐带间充质干细胞(UC-MSCs)移植治疗肝纤维化的疗效。方法：分离培养的人UC-MSCs，输注于二甲基亚硝胺(DMN)诱导的大鼠肝纤维化模型。观察输注UC-MSCs对大鼠肝纤维化的影响，并检测血清IL-4、IL-10水平。分离和培养肝纤维化组织中的Kupffer细胞(KCs)，分析其表型。此外，将UC-MSCs与KCs体外共培养，观察UC-MSCs对KCs表型的影响，并检测细胞培养上清液中IL-4和IL-10的水平。最后在IL-4抗体存在下培养UC-MSCs和KCs，以阻断该细胞因子的作用，并对KC进行表型分析。结果：输注UC-MSCs的大鼠被损伤的肝脏招募，并减轻肝纤维化，提高血清IL-4和IL-10水平。有趣的是，UC-MSCs不仅在纤维化的肝脏中促进KCs的动员，而且在体外也促进KCs的动员。UC-MSCs与KCs共培养可增加IL-4和IL-10的产生。联合培养体系中加入IL-4抗体后，KC动员能力下降。结论：UC-MSCs在体内外均能提高IL-4水平，促进KC动员，从而减轻DMN诱导的肝纤维化。
AIM: To evaluate the efficacy of umbilical cord-derived mesenchymal stem cells (UC-MSCs) transplantation in the treatment of liver fibrosis.METHODS: Cultured human UC-MSCs were isolated and transfused into rats with liver fibrosis induced by dimethylnitrosamine (DMN). The effects of UC-MSCs transfusion on liver fibrosis were then evaluated by histopathology; serum interleukin (IL)-4 and IL-10 levels were also measured. Furthermore, Kupffer cells (KCs) in fibrotic livers were isolated and cultured to analyze their phenotype. Moreover, UC-MSCs were co-cultured with KCs in vitro to assess the effects of UC-MSCs on KCs' phenotype, and IL-4 and IL-10 levels were measured in cell culture supernatants. Finally, UC-MSCs and KCs were cultured in the presence of IL-4 antibodies to block the effects of this cytokine, followed by phenotypical analysis of KCs.RESULTS: UC-MSCs transfused into rats were recruited by the injured liver and alleviated liver fibrosis, increasing serum IL-4 and IL-10 levels. Interestingly, UC-MSCs promoted mobilization of KCs not only in fibrotic livers, but also in vitro. Co-culture of UC-MSCs with KCs resulted in increased production of IL-4 and IL-10. The addition of IL-4 antibodies into the co-culture system resulted in decreased KC mobilization.CONCLUSION: UC-MSCs could increase IL-4 and promote mobilization of KCs both in vitro and in vivo, subsequently alleviating the liver fibrosis induced by DMN.