PDF(Pubmed)
Abstract：
Osteoarthritis (OA) is a degenerative disease that significantly impairs quality of life. There is a pressing need for innovative OA therapies. While small extracellular vesicles (sEVs) show promising therapeutic effects against OA, their limited yield restricts clinical translation. Here, we devised a novel production system for sEVs that enhances both their yield and therapeutic properties. By stimulating mesenchymal stem cells (MSCs) using electromagnetic field (EMF) combined with ultrasmall superparamagnetic iron oxide (USPIO) particles, we procured an augmented yield of EMF-USPIO-sEVs. These vesicles not only activate anabolic pathways but also inhibit catabolic activities, and crucially, they promote M2 macrophage polarization, aiding cartilage regeneration. In an OA mouse model triggered by anterior cruciate ligament transection surgery, EMF-USPIO-sEVs reduced OA severity, and augmented matrix synthesis. Moreover, they decelerated OA progression through the microRNA-99b/MFG-E8/NF-κB signaling axis. Consequently, EMF-USPIO-sEVs present a potential therapeutic option for OA, acting by modulating matrix homeostasis and macrophage polarization.
摘要：
骨关节炎（OA）是一种严重损害生活质量的退行性疾病。迫切需要创新的OA疗法。虽然小的细胞外囊泡（sEV）对OA显示出有希望的治疗效果，它们有限的产量限制了临床翻译。这里,我们设计了一种新型的sEV生产系统，可以提高其产量和治疗性能。通过使用电磁场（EMF）结合超小超顺磁性氧化铁（USPIO）颗粒刺激间充质干细胞（MSC），我们获得了提高的EMF-USPIO-sEV产量。这些囊泡不仅激活合成代谢途径，而且抑制分解代谢活性，至关重要的是,它们促进M2巨噬细胞极化，辅助软骨再生。在前交叉韧带横断手术引发的OA小鼠模型中，EMF-USPIO-sEV降低OA严重程度，和增广矩阵合成。此外，他们通过microRNA-99b/MFG-E8/NF-κB信号轴减缓OA的进展.因此,EMF-USPIO-sEV为OA提供了一种潜在的治疗选择，通过调节基质稳态和巨噬细胞极化。
