Exosome inspired photo-triggered gelation hydrogel composite on modulating immune pathogenesis for treating rheumatoid arthritis.

Exosome inspired photo-triggered gelation hydrogel composite on modulating immune pathogenesis for treating rheumatoid arthritis.
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外泌体激发的光触发凝胶化水凝胶复合物调节免疫发病机制以治疗类风湿性关节炎。

DOI:
10.1186/s12951-023-01865-8
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发表时间:
2023-03-28
影响因子:
10.2
通讯作者:
Yang, Yumin
Yang, Yumin
中科院分区:
工程技术1区
文献类型:
--
作者:
Rui, Ke;Tang, Xiaoxuan;Shen, Ziwei;Jiang, Chao;Zhu, Qiugang;Liu, Shiyi;Che, Nan;Tian, Jie;Ling, Jue;Yang, Yumin

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尽管外泌体治疗已被认为是治疗类风湿性关节炎(RA)的一种有前途的策略,但持续调节RA特异性发病机制和减轻关节破坏的理想保护作用仍然存在挑战。在此,将包封有嗅觉外间充质干细胞衍生的外泌体(Exos@SFMA)的丝素蛋白水凝胶原位光交联以产生调节RA中的免疫微环境的持久治疗效果。这种原位水凝胶系统具有灵活的机械性能和良好的生物相容性,可用于保护关节中的组织表面。此外,在外泌体上鉴定出有希望的PD-L1表达,其通过抑制PI 3 K/AKT通路而有力地抑制Tfh细胞极化。重要的是,Exos@SFMA通过显著降低T滤泡辅助(Tfh)细胞反应并进一步抑制生发中心(GC)B细胞分化为浆细胞,有效缓解了滑膜炎症和关节破坏。总之,这种外泌体增强的丝素蛋白水凝胶为治疗RA和其他自身免疫性疾病提供了有效的策略。在线版本包含补充材料,可通过10.1186/s12951-023-01865-8获得。
Although exosome therapy has been recognized as a promising strategy in the treatment of rheumatoid arthritis (RA), sustained modulation on RA specific pathogenesis and desirable protective effects for attenuating joint destruction still remain challenges. Here, silk fibroin hydrogel encapsulated with olfactory ecto-mesenchymal stem cell-derived exosomes (Exos@SFMA) was photo-crosslinked in situ to yield long-lasting therapeutic effect on modulating the immune microenvironment in RA. This in situ hydrogel system exhibited flexible mechanical properties and excellent biocompatibility for protecting tissue surfaces in joint. Moreover, the promising PD-L1 expression was identified on the exosomes, which potently suppressed Tfh cell polarization via inhibiting the PI3K/AKT pathway. Importantly, Exos@SFMA effectively relieved synovial inflammation and joint destruction by significantly reducing T follicular helper (Tfh) cell response and further suppressing the differentiation of germinal center (GC) B cells into plasma cells. Taken together, this exosome enhanced silk fibroin hydrogel provides an effective strategy for the treatment of RA and other autoimmune diseases. The online version contains supplementary material available at 10.1186/s12951-023-01865-8.
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