Zhao Yongzhao, Chen Longting, Jiang Shuai, Wu Zhenquan, Xiang Qian, Lin Jialiang, Tian Shuo, Sun Zhuoran, Sun Chuiguo, Li Weishi
Department of Orthopaedics, Peking University Third Hospital, Beijing, China.
Beijing Key Laboratory of Spinal Disease Research, Beijing, China.
Bioact Mater. 2025 Mar 20;49:515-530. doi: 10.1016/j.bioactmat.2025.02.046. eCollection 2025 Jul.
Intervertebral disc degeneration (IDD) is the leading cause of low back pain, which places heavy burdens on society and individuals. Surgical intervention is the conventional therapy for IDD, but patients who undergo surgery face relatively high risks of recurrence and complications. Therefore, a relatively less invasive and efficient treatment for IDD is urgently needed. In this study, we constructed a novel nanobiomaterial, named Hi-Exos, to slow IDD. Hi-Exos are exosomes derived from mesenchymal stem cells exposed to hypoxic and inflammatory environments. Hi-Exos could relieve the senescence of nucleus pulposus cells and slow IDD through an epigenetic modification mechanism by introducing the epigenetic factor miR-221-3p into senescent nucleus pulposus cells to reduce DDIT4 expression and inhibit the activation of NF-κB signalling pathway. This study provided a novel strategy for IDD treatment involving the use of Hi-Exos to deliver miR-221-3p to reduce the senescence of nucleus pulposus cells and repair IDD via epigenetic modifications.
椎间盘退变（IDD）是腰痛的主要原因，给社会和个人带来了沉重负担。手术干预是IDD的传统治疗方法，但接受手术的患者面临相对较高的复发和并发症风险。因此，迫切需要一种侵入性相对较小且高效的IDD治疗方法。在本研究中，我们构建了一种名为Hi-Exos的新型纳米生物材料来延缓IDD。Hi-Exos是源自暴露于缺氧和炎症环境的间充质干细胞的外泌体。Hi-Exos可以通过将表观遗传因子miR-221-3p引入衰老的髓核细胞以降低DDIT4表达并抑制NF-κB信号通路的激活，通过表观遗传修饰机制缓解髓核细胞衰老并延缓IDD。本研究为IDD治疗提供了一种新策略，即利用Hi-Exos递送miR-221-3p，通过表观遗传修饰减少髓核细胞衰老并修复IDD。
