Extracellular Vesicles From TNFα Preconditioned MSCs: Effects on Immunomodulation and Bone Regeneration.
Extracellular Vesicles From TNFα Preconditioned MSCs: Effects on Immunomodulation and Bone Regeneration.
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DOI：
10.3389/fimmu.2022.878194
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
--
作者：
间充质干细胞表现出显着的多功能性，并通过改变其表型和行为来响应细胞外和微环境线索。在这方面，MSC在组织修复中的免疫调节特性是有据可查的。MSC在免疫调节中的旁分泌作用部分归因于其分泌的细胞外囊泡（EV）。当MSC迁移到伤口床时，它们暴露于无数的炎症信号。为了从EV的角度了解它们对炎症环境的反应，我们试图评估炎性细胞因子TNFα对MSC EV介导的免疫调节的影响。我们的结果表明，虽然EV的物理特性保持不变，但TNFα预处理的MSC EV具有增强的免疫调节特性。使用极化（M1和M2）原代小鼠巨噬细胞的体外实验表明，预处理的MSC EV抑制促炎（M1）标志物如IL-1β和iNOS，并升高修复（M2）标志物如Arg 1和CD 206。当在大鼠颅骨缺损模型中进行体内评估时，TNFα预处理的MSC EV在创伤后1天、3天和7天减少炎症，导致随后在创伤后4周和8周增强骨形成，这可能是通过调节制瘤素M（OSM）表达实现的。EV miRNA组成的分析揭示了预处理的MSC EV中抗炎miRNA的显著变化，暗示EV衍生的miRNA在增强的免疫调节活性中的可能作用。总之，这些结果表明，MSC暴露于炎症信号影响MSC EV在组织修复背景下的免疫调节功能。TNFα预处理的MSC EV miRNAs在骨再生的免疫调节控制中的特异性功能值得进一步研究。
Mesenchymal stem cells show remarkable versatility and respond to extracellular and micro environmental cues by altering their phenotype and behavior. In this regard, the MSC’s immunomodulatory properties in tissue repair are well documented. The paracrine effects of MSCs in immunomodulation are, in part, attributable to their secreted extracellular vesicles (EVs). When MSCs migrate to the wound bed, they are exposed to a myriad of inflammatory signals. To understand their response to an inflammatory environment from an EV perspective, we sought to evaluate the effects of the inflammatory cytokine TNFα on MSC EV mediated immunomodulation. Our results indicate that while the physical characteristics of the EVs remain unchanged, the TNFα preconditioned MSC EVs possess enhanced immunomodulatory properties. In vitro experiments using polarized (M1 and M2) primary mouse macrophages indicated that the preconditioned MSC EVs suppressed pro-inflammatory (M1) markers such as IL-1β and iNOS and elevated reparatory (M2) markers such as Arg1 and CD206. When evaluated in vivo in a rat calvarial defect model, the TNFα preconditioned MSC EVs reduced inflammation at 1-, 3- and 7-days post wounding resulting in the subsequent enhanced bone formation at 4- and 8-weeks post wounding possibly by modulation of oncostatin M (OSM) expression. An analysis of EV miRNA composition revealed significant changes to anti-inflammatory miRNAs in the preconditioned MSC EVs hinting at a possible role for EV derived miRNA in the enhanced immunomodulatory activity. Overall, these results indicate that MSC exposure to inflammatory signals influence the MSC EV’s immunomodulatory function in the context of tissue repair. The specific function of TNFα preconditioned MSC EV miRNAs in immunomodulatory control of bone regeneration merits further investigation.
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影响因子：
3.5
作者：
Katagiri W;Takeuchi R;Saito N;Suda D;Kobayashi T
通讯作者：
Kobayashi T
DOI：
10.1073/pnas.1018501108
发表时间：
2011-01-25
影响因子：
11.1
作者：
Glass, Graeme E.;Chan, James K.;Nanchahal, Jagdeep
通讯作者：
Nanchahal, Jagdeep
影响因子：
5.5
作者：
Kang M;Thalji G;Huang CC;Shirazi S;Lu Y;Ravindran S;Cooper LF
通讯作者：
Cooper LF
影响因子：
3.6
作者：
Kim, Mijin;Shin, Dong Il;Min, Byoung-Hyun
通讯作者：
Min, Byoung-Hyun
影响因子：
5.6
作者：
Matheakakis A;Batsali A;Papadaki HA;Pontikoglou CG
通讯作者：
Pontikoglou CG