Transplantation of adipose-derived stem cells ameliorates Echinococcus multilocularis-induced liver fibrosis in mice.
Transplantation of adipose-derived stem cells ameliorates Echinococcus multilocularis-induced liver fibrosis in mice.
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脂肪干细胞移植可改善多房棘球蚴诱导的小鼠肝纤维化
DOI：
10.1371/journal.pntd.0010175
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发表时间：
2022-01
影响因子：
3.8
通讯作者：
Lin R
中科院分区：
文献类型：
--
作者：
Yang N;Ma W;Ke Y;Liu H;Chu J;Sun L;Lü G;Bi X;Lin R
泡状棘球蚴病（AE）可导致严重的肝纤维化，如果不治疗可能是致命的。目前，对于AE诱导的肝纤维化没有有效的治疗选择。鉴于脂肪干细胞（ADSCs）的治疗潜力，我们研究了ADSCs移植是否具有控制或逆转多房棘球绦虫（E.多房性）感染的小鼠。C57 BL/6小鼠感染E.通过门静脉接种的多房小鼠静脉内注射从6-8周龄小鼠的腹股沟脂肪组织分离的ADSC。采用苏木精-伊红染色、Masson三色染色、天狼星红染色等组织学方法观察肝纤维化程度。ADSCs移植后30天的肝组织学检查显示，ADSCs可显著减轻E.通过抑制α-SMA的表达和Ⅰ型胶原沉积，抑制多房性巨噬细胞的增殖。此外，与非移植组相比，ADSCs移植减少了E.感染小鼠。ADSCs移植后TGF-β1和TGF-βR的表达明显下调，而TGF-β/Smad信号通路中Smad 7的表达明显上调。ADSCs可通过调节TGF-β/Smad 7信号通路的活性水平来减轻泡球蚴感染诱导的肝纤维化，为泡球蚴病的治疗提供了一种潜在的途径。多房性纤维化泡状棘球蚴病是北方发达国家和发展中国家最致命的人畜共患病之一。多房的）。这种疾病的特征是病变周围严重纤维化的发展，逐渐取代正常的肝实质并影响肝功能。间充质干细胞（MSC）已被评估为组织修复（包括纤维化）的替代治疗选择。脂肪源性干细胞（Adipose-derived stem cells，ADSCs）是间充质干细胞（MSCs）的一个亚群，可以通过吸脂术从脂肪组织中获得，这意味着可以通过创伤较小的手术获得大量细胞。在多种组织中，包括肺、皮肤、肾，特别是肝组织，ADSC已被证明在纤维化治疗中有效。因此，我们研究了脂肪干细胞对多房棘球绦虫感染的治疗潜力。简而言之，E.发现移植了ADSC的多房感染小鼠的肝纤维化程度较低，表明ADSC作为E.多房性肝纤维化虽然这些发现是有希望的，但应使用长期AE感染模型进行研究以确认ADSC对AE的治疗效果。
Alveolar echinococcosis (AE) can cause severe liver fibrosis and could be fatal if left untreated. Currently, there are no effective therapeutic options for AE-induced liver fibrosis. In view of the therapeutic potential of adipose-derived stem cells (ADSCs), we investigated whether ADSCs transplantation has the ability to control or reverse fibrosis progression in the liver of Echinococcus multilocularis (E. multilocularis) infected mice. C57BL/6 mice infected with E. multilocularis through portal vein inoculation were intravenously injected with ADSCs isolated from inguinal adipose tissues of 6–8 weeks old mice. Histopathological analysis including heamatoxylin & eosin staining as well as Masson’s trichrome staining, and Sirius red staining were performed to access the degree of liver fibrosis. Histopathological examination 30 days after ADSCs transplantation revealed that ADSCs significantly decreased the degree of liver fibrosis in E. multilocularis infected mice by inhibiting the expressions of α-SMA and type 1 collagen deposition. In addition, compared to the non-transplanted group, ADSCs transplantation reduced fibrotic areas in E. multilocularis infected mice. We also found that ADSCs transplantation significantly down-regulated TGF-β1 and TGF-βR expressions, while up-regulating Smad7 expression in the TGF-β/Smad signaling pathway. ADSCs can alleviate Echinococcus multilocularis infection-induced liver fibrosis by modulating the activity level of the TGF-β/Smad7 signaling pathway and provide a potential therapeutic approach for E. multilocularis-induced fibrosis. Alveolar echinococcosis (AE), one of the most deadly zoonoses in both developing and developed Northern Hemisphere countries, is caused by the larval stages (metacestode) of the tapeworm Echinococcus multilocularis (E. multilocularis). This disease is characterized by the development of severe fibrosis around the lesion, which gradually replaces normal liver parenchyma and affects liver function. Mesenchymal stem cells (MSCs) have been evaluated as an alternative therapeutic option for tissue repair (including fibrosis). Adipose-derived stem cells (ADSCs), which are one of MSCs subsets, can easily obtained from adipose tissues through liposuction, implying that a large number of cells can be obtained with less traumatic surgery. In multiple tissues, including pulmonary, dermal, renal, and especially liver tissues, ADSCs have been shown to be effective in fibrosis treatment. Therefore, we investigated the therapeutic potential of ADSCs on Echinococcus multilocularis infections. Briefly, E. multilocularis-infected mice that were transplanted with ADSCs were found to have less liver fibrosis, indicating the potential of ADSCs as novel therapeutic approaches for E. multilocularis-induced liver fibrosis. Although these findings are promising, studies using long-term AE infection models should be performed to confirm the therapeutic effects of ADSCs on AE.
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