Small Extracellular Vesicles Derived From MSCs Have Immunomodulatory Effects to Enhance Delivery of ASO-210 for Psoriasis Treatment.
Small Extracellular Vesicles Derived From MSCs Have Immunomodulatory Effects to Enhance Delivery of ASO-210 for Psoriasis Treatment.
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DOI：
10.3389/fcell.2022.842813
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发表时间：
2022
影响因子：
5.5
通讯作者：
Cheng F
中科院分区：
文献类型：
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作者：
Zhang W;Lin J;Shi P;Su D;Cheng X;Yi W;Yan J;Chen H;Cheng F
间充质干细胞（MSC）因其免疫调节功能而越来越多地用于治疗自身免疫性疾病，但其归巢效率低和安全问题限制了其广泛应用。最近，越来越多的研究表明，小细胞外囊泡（sEV）是间充质干细胞发挥免疫调节作用的关键介质。在这项研究中，我们发现IFN-γ刺激的人脐带间充质干细胞衍生的sEV（IFNγ-sEV）在体外抑制外周血单核细胞和T细胞的增殖和活化。此外，我们证实 IFNγ-sEV 可以减轻银屑病症状，包括皮损厚度、红斑和鳞屑； Th17细胞耗尽，Th2细胞增加；体内脾脏和皮肤病变中炎症细胞因子（如 IL-17A、IFN-γ、IL-6 和 TNF-α）的富集减少。重要的是，IFNγ-sEVs显着提高了ASO-210的递送效率和稳定性，miR-210的反义寡核苷酸阻断了免疫失衡和随后的银屑病发展。我们的结果表明 MSC-sEV 是有前途的无细胞治疗剂和用于治疗银屑病的反义寡核苷酸的理想递送载体。
Mesenchymal stem cells (MSCs) have been increasingly used for treating autoimmune diseases due to their immune modulation functions, but inefficient homing to the target tissue and safety issues limits their wide application. Recently, increasing studies demonstrate small extracellular vesicles (sEVs) as key mediators of MSCs to exert their immunomodulatory effects. In this study, we found that sEVs derived from human umbilical cord MSCs stimulated by IFN-γ (IFNγ-sEVs) inhibited proliferation and activation of peripheral blood mononuclear cells and T cells in vitro. Furthermore, we confirmed that IFNγ-sEVs reduced psoriasis symptoms including thickness, erythema, and scales of skin lesions; exhausted Th17 cells, increased Th2 cells; and reduced enrichment of inflammatory cytokines such as IL-17A, IFN-γ, IL-6, and TNF-α in both spleen and skin lesions in vivo. Importantly, IFNγ-sEVs significantly improved the delivery efficiency and stability of ASO-210, the antisense oligonucleotides of miR-210 block the immune imbalance and subsequent psoriasis development. Our results reveal MSC-sEVs as promising cell-free therapeutic agents and ideal delivery vehicles of antisense oligonucleotides for psoriasis treatment.
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DOI：
10.1002/advs.202102634
发表时间：
2022-01
期刊：
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
影响因子：
--
作者：
Tsai HI;Wu Y;Liu X;Xu Z;Liu L;Wang C;Zhang H;Huang Y;Wang L;Zhang W;Su D;Khan FU;Zhu X;Yang R;Pang Y;Eriksson JE;Zhu H;Wang D;Jia B;Cheng F;Chen H
通讯作者：
Chen H
间充质干细胞衍生的外泌体：生物学功能及其在辐射损伤中的治疗潜力
影响因子：
6
作者：
Pu X;Ma S;Gao Y;Xu T;Chang P;Dong L
通讯作者：
Dong L
影响因子：
16
作者：
Witwer, Kenneth W.;Van Balkom, Bas W. M.;Lim, Sai Kiang
通讯作者：
Lim, Sai Kiang
影响因子：
6.5
作者：
Chiricozzi, Andrea;Guttman-Yassky, Emma;Krueger, James G.
通讯作者：
Krueger, James G.
DOI：
10.1038/jid.2009.399
发表时间：
2010-05
期刊：
The Journal of investigative dermatology
影响因子：
--
作者：
通讯作者：
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