Extracellular vesicles (EVs) are membrane vesicles released virtually by all cell types. Several studies have shown that stem cell-derived EVs may mimic both in vitro and in vivo the biological effects of the cells. We recently demonstrated that non-alcoholic steatohepatitis (NASH) is inhibited by treatment with human liver stem cells (HLSCs). The aim of the present study was to evaluate whether EVs released by HLSCs influence the progression of NASH, induced by a diet deprived of methionine and choline, in immunocompromised mice. EV treatment was initiated after 2 weeks of diet with a biweekly administration of three different doses. Bio-distribution evaluated by optical imaging showed a preferential accumulation in normal and, in particular, in fibrotic liver. EV treatment significantly improved liver function and reduced signs of liver fibrosis and inflammation at both morphological and molecular levels. In particular, we observed that, out of 29 fibrosis-associated genes upregulated in NASH liver, 28 were significantly downregulated by EV treatment. In conclusion, HLSC-derived EVs display anti-fibrotic and anti-inflammatory effects in a model of chronic liver disease, leading to an improvement of liver function.

中文翻译：

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HLSC衍生的细胞外囊泡可在非酒精性脂肪性肝炎的小鼠模型中减轻肝纤维化和炎症。

细胞外囊泡（EVs）实际上是所有细胞类型释放的膜囊泡。多项研究表明，干细胞衍生的电动汽车可以在体外和体内模拟细胞的生物学效应。我们最近证明，非酒精性脂肪性肝炎（NASH）被人肝干细胞（HLSCs）抑制。本研究的目的是评估免疫功能低下的小鼠中，HLSC释放的电动汽车是否会影响由缺乏蛋氨酸和胆碱的饮食诱导的NASH的进展。饮食2周后开始进行EV治疗，每两周施用三种不同剂量。通过光学成像评估的生物分布显示出在正常且特别是在肝纤维化肝脏中的优先积累。EV治疗在形态和分子水平上均显着改善了肝功能，并减少了肝纤维化和炎症的迹象。尤其是，我们观察到，在NASH肝中上调的29个与纤维化相关的基因中，有28个通过EV治疗而显着下调。总之，HLSC衍生的电动汽车在慢性肝病模型中显示出抗纤维化和抗炎作用，从而改善了肝功能。