Exosomes derived from MSCs exposed to hypoxic and inflammatory environments slow intervertebral disc degeneration by alleviating the senescence of nucleus pulposus cells through epigenetic modifications
Yongzhao Zhao, Longting Chen, Shuai Jiang, Zhenquan Wu, Qian Xiang, Jialiang Lin, Shuo Tian, Zhuoran Sun, Chuiguo Sun, Weishi Li
Abstract
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. • Hi-Exos was superior to Exos in relieving the senescence of nucleus pulposus cells and intervertebral disc degeneration. • Epigenetic factor miR-221-3p played an important role in intervertebral disc degeneration. • Hi-Exos transferred the miR-221-3p to inhibit the DDIT4/NF-κB pathway. • Hi-Exos provided a novel strategy for intervertebral disc degeneration.