Institute of Medical Immunology, Affiliated Hospital of Jiangsu University, Zhenjiang, China.
Key Laboratory of Neuroregeneration, Co-innovation Center of Neuroregeneration, Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Ministry of Education and Jiangsu Province, Nantong University, Nantong, China.
J Nanobiotechnology. 2023 Mar 28;21(1):111. doi: 10.1186/s12951-023-01865-8.
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.
尽管外泌体治疗已被认为是治疗类风湿关节炎 (RA) 的一种有前途的策略，但持续调节 RA 的特定发病机制和减轻关节破坏的理想保护作用仍然是挑战。在这里，丝素蛋白水凝胶包裹着嗅外胚层间充质干细胞衍生的外泌体 (Exos@SFMA) 被原位光交联，从而对调节 RA 中的免疫微环境产生持久的治疗效果。这种原位水凝胶系统具有灵活的机械性能和优异的生物相容性，可保护关节表面的组织。此外，外泌体上鉴定出有前途的 PD-L1 表达，通过抑制 PI3K/AKT 途径，强力抑制滤泡辅助性 T 细胞 (Tfh) 极化。重要的是，Exos@SFMA 通过显著减少滤泡辅助性 T 细胞 (Tfh) 反应并进一步抑制生发中心 (GC) B 细胞向浆细胞的分化，有效缓解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一种有效的策略。
