Mesenchymal-Stem-Cell-Derived Extracellular Vesicles Mitigate Trained Immunity in the Brain.
Mesenchymal-Stem-Cell-Derived Extracellular Vesicles Mitigate Trained Immunity in the Brain.
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间充质干细胞衍生的细胞外囊泡可减轻大脑中经过训练的免疫力
DOI：
10.3389/fbioe.2020.599058
复制
发表时间：
2020
影响因子：
5.7
通讯作者：
Cui M
中科院分区：
文献类型：
--
作者：
Feng Y;Guo M;Zhao H;Han S;Dong Q;Cui M
最近在先天免疫细胞中发现了训练有素的免疫力，并被证明可以在第二次损伤发生时促进病原体的清除。然而，它会加剧神经病理学的几个方面，需要适当的治疗来纠正这种异常的免疫反应。间充质干细胞（MSC）表现出独特的脑修复能力，但存在安全问题。间充质干细胞衍生的细胞外囊泡是一种有前途的替代疗法。在这项研究中，我们使用脂多糖来激活大脑中经过训练的免疫力，并检查了 MSC 衍生的细胞外囊泡在减轻经过训练的免疫引起的神经病理学恶化方面的治疗潜力。我们发现，间充质干细胞衍生的细胞外囊泡在减轻大脑中训练有素的免疫力方面表现出与间充质干细胞相当的效果。此外，给予 MCS 来源的细胞外囊泡可减轻中风急性期的聚集炎症反应，并减轻 APP/PS1 小鼠中免疫训练诱导的淀粉样蛋白-β 负荷增加。我们进一步研究了 MSC 衍生的细胞外囊泡的分子机制，发现 IL-10 对于介导 MSC 衍生的细胞外囊泡的治疗潜力以减轻训练有素的免疫力非常重要。我们的研究表明，基于细胞外囊泡的再生策略可能有助于减轻大脑中经过训练的免疫力。
Trained immunity was recently discovered in innate immune cells and shown to facilitate the clearance of pathogens at the time of occurrence of the second insult. However, it exacerbates several aspects of neuropathologies, and proper therapy is needed to rectify this abnormal immune reaction. Mesenchymal-stem cells (MSCs) exhibit a distinct capability for brain repair but are associated with safety concerns. Extracellular vesicles derived from MSCs are a promising alternative therapy. In this study, we used lipopolysaccharides to activate trained immunity in the brain and examined the therapeutic potential of MSC-derived extracellular vesicles in mitigating the trained-immunity-induced exacerbated neuropathology. We found that MSC-derived extracellular vesicles showed comparable effects to those of MSCs in the mitigation of trained immunity in the brain. Moreover, the administration of MCS-derived extracellular vesicles mitigated the aggregated inflammatory responses in the acute stage of stroke and alleviated the trained-immunity-induced increased load of amyloid-β in APP/PS1 mice. We further investigated the molecular machinery of MSC-derived extracellular vesicles and found that IL-10 is important for the mediation of the therapeutic potential of MSC-derived extracellular vesicles toward the alleviation of trained immunity. Our study indicates that extracellular-vesicle-based regenerative strategies might be useful to mitigate trained immunity in the brain.
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DOI：
10.1016/j.apsb.2016.02.001
发表时间：
2016-07
期刊：
Acta pharmaceutica Sinica. B
影响因子：
--
作者：
Ha D;Yang N;Nadithe V
通讯作者：
Nadithe V
影响因子：
15.1
作者：
Rutherford NJ;Sacino AN;Brooks M;Ceballos-Diaz C;Ladd TB;Howard JK;Golde TE;Giasson BI
通讯作者：
Giasson BI
hUCMSC 减轻缺血性中风中 LPS 诱导的训练免疫
影响因子：
7.3
作者：
Feng YW;Wu C;Liang FY;Lin T;Li WQ;Jing YH;Dai P;Yu HX;Lan Y;Pei Z;Xu GQ
通讯作者：
Xu GQ
影响因子：
7.5
作者：
Park, Kyong-Su;Svennerholm, Kristina;Lotvall, Jan
通讯作者：
Lotvall, Jan
影响因子：
8.3
作者：
Chen J;Chopp M
通讯作者：
Chopp M