Exosomes from umbilical cord mesenchymal stem cells ameliorate intervertebral disc degeneration via repairing mitochondrial dysfunction

作者：Shu Jia, Tao Yang, Sheng Gao, Luyue Bai, Zhiguo Zhu, Siqi Zhao, Yexin Wang, Xiao Liang, Yanpeng Li, Longfei Gao, Zifang Zhang, Xu Gao, Dongru Li, Shang Chen, Bin Zhang, Chunyang Meng · 发表于：Journal of Orthopaedic Translation · 年份：2024 · DOI：10.1016/j.jot.2023.10.004 · 被引用次数：23 · 研究领域：Spine and Intervertebral Disc Pathology、Cervical and Thoracic Myelopathy、Spinal Cord Injury Research

Reactive oxygen species (ROS), predominantly generated by mitochondria, play a crucial role in the pathogenesis of intervertebral disc degeneration (IVDD). Reduction of ROS levels may be an effective strategy to delay IVDD. In this study, we assessed whether umbilical cord mesenchymal stem cell-exosomes (UCMSC-exos) can be used to treat IVDD by suppressing ROS production caused by mitochondrial dysfunction. Human UCMSC-exos were isolated and identified. Nucleus pulposus cells (NPCs) were stimulated with H2O2 in the presence or absence of exosomes. Then, 4D label free quantitative (4D-LFQ) proteomics were used to analyze the differentially expressed (DE) proteins. Mitochondrial membrane potential (MMP), mitochondrial ROS and protein levels were determined via immunofluorescence staining, flow cytometry and western blotting respectively. Additionally, high-throughput sequencing was performed to identify the DE miRNAs in NPCs. Finally, therapeutic effects of UCMSC-exos were investigated in a puncture-induced IVDD rat model. Degenerative grades of rat IVDs were assessed using magnetic resonance imaging and histochemical staining. UCMSC-exos effectively improved the viability of NPCs and restored the expression of the extracellular matrix (ECM) proteins, collagen type II alpha-1 (COL2A1) and matrix metalloproteinase-13 induced by H2O2. Additionally, UCMSC-exos not only reduced the total intracellular ROS and mitochondrial superoxide levels, but also increased MMP in pathological N...