Exosomes derived from three-dimensional cultured human umbilical cord mesenchymal stem cells ameliorate pulmonary fibrosis in a mouse silicosis model.
Exosomes derived from three-dimensional cultured human umbilical cord mesenchymal stem cells ameliorate pulmonary fibrosis in a mouse silicosis model.
复制标题
三维培养人脐带间充质干细胞来源的外泌体改善小鼠矽肺模型中的肺纤维化
DOI：
10.1186/s13287-020-02023-9
复制
发表时间：
2020-11-25
影响因子：
7.5
通讯作者：
Tian L
中科院分区：
文献类型：
--
作者：
Xu C;Zhao J;Li Q;Hou L;Wang Y;Li S;Jiang F;Zhu Z;Tian L
矽肺是一种因长期过量吸入二氧化硅而引起的职业性呼吸道疾病，最常见于工业环境中。不幸的是，没有有效的治疗方法来延缓和治愈矽肺的进展。近年来，干细胞治疗因其独特的生物学特性而成为治疗肺纤维化（PF）的一种有吸引力的工具。然而，直接使用干细胞仍然受到许多风险因素的限制。从干细胞，而不是细胞分泌的外泌体的独家效用，已被认为是一个有前途的替代方案，以克服基于细胞的治疗的局限性，同时保持其优点。方法和resultsIn这项研究中，我们首先采用了三维（3D）动态系统培养人脐带间充质干细胞（hucMSC）球状体在微载体悬浮液产生外泌体从无血清培养基。在C57 BL/6 J小鼠中通过气管内滴注二氧化硅悬浮液诱导实验性硅肺，所述二氧化硅悬浮液具有/不具有源自hucMSC的外来体（hucMSC-Exos），之后经由尾静脉注射。结果显示，与对照组相比，二氧化硅组中I型胶原（COL 1A 1）和纤连蛋白（FN）的基因表达上调;然而，这种变化随着hucMSC-Exo处理而减弱。与对照组相比，二氧化硅组的FEV0.1值降低，并且这种变化随着hucMSC-Exo治疗而减弱。这些结果表明，hucMSC-Exos可以抑制二氧化硅诱导的PF并调节肺功能。我们还进行了体外实验，以证实这些发现;结果显示，hucMSC-Exos减少胶原沉积在NIH-3 T3细胞暴露于silica.ConclusionsTaken在一起，这些研究支持hucMSC-Exos在改善肺纤维化的潜在作用，并为改善二氧化硅诱导的临床治疗提供了新的证据。
BackgroundSilicosis is an occupational respiratory disease caused by long-term excessive silica inhalation, which is most commonly encountered in industrial settings. Unfortunately, there is no effective therapy to delay and cure the progress of silicosis. In the recent years, stem cell therapy has emerged as an attractive tool against pulmonary fibrosis (PF) owing to its unique biological characteristics. However, the direct use of stem cells remains limitation by many risk factors for therapeutic purposes. The exclusive utility of exosomes secreted from stem cells, rather than cells, has been considered a promising alternative to overcome the limitations of cell-based therapy while maintaining its advantages.Methods and resultsIn this study, we first employed a three-dimensional (3D) dynamic system to culture human umbilical cord mesenchymal stem cell (hucMSC) spheroids in a microcarrier suspension to yield exosomes from serum-free media. Experimental silicosis was induced in C57BL/6J mice by intratracheal instillation of a silica suspension, with/without exosomes derived from hucMSC (hucMSC-Exos), injection via the tail vein afterwards. The results showed that the gene expression of collagen I (COL1A1) and fibronectin (FN) was upregulated in the silica group as compared to that in the control group; however, this change decreased with hucMSC-Exo treatment. The value of FEV0.1 decreased in the silica group as compared to that in the control group, and this change diminished with hucMSC-Exo treatment. These findings suggested that hucMSC-Exos could inhibit silica-induced PF and regulate pulmonary function. We also performed in vitro experiments to confirm these findings; the results revealed that hucMSC-Exos decreased collagen deposition in NIH-3T3 cells exposed to silica.ConclusionsTaken together, these studies support a potential role for hucMSC-Exos in ameliorating pulmonary fibrosis and provide new evidence for improving clinical treatment induced by silica.
登录
查看更多内容
影响因子：
17.1
作者：
Hu, Shiqi;Li, Zhenhua;Cheng, Ke
通讯作者：
Cheng, Ke
影响因子：
3
作者：
Frith, Jessica E.;Thomson, Brian;Genever, Paul G.
通讯作者：
Genever, Paul G.
影响因子：
10.6
作者：
Chanda D;Otoupalova E;Smith SR;Volckaert T;De Langhe SP;Thannickal VJ
通讯作者：
Thannickal VJ
DOI：
10.1152/ajplung.00492.2005
发表时间：
2006-08-01
影响因子：
4.9
作者：
Lovgren, Alysia Kern;Jania, Leigh A.;Koller, Beverly H.
通讯作者：
Koller, Beverly H.
MicroRNA-29b 介导硅肺模型中的肺间质-上皮转化并预防肺纤维化
影响因子：
8.8
作者：
Sun, Jingping;Li, Qiuyue;Tian, Lin
通讯作者：
Tian, Lin