MiR-124 Delivered by Extracellular Vesicles from Mesenchymal Stem Cell Exerts Neuroprotective Effects by Stabilizing the p62-Keap1-Nrf2 Pathway after Spinal Cord Injury in Rats

  • Mol Neurobiol. 2025 Jul;62(7):8328-8340. doi: 10.1007/s12035-025-04755-2.
Chao Fang  1 ,  Jun Qian  2 ,  Bi-Zhi Tu  3 ,  Xiang Xia  2 ,  Chong-Yu Jia  2 ,  Cai-Liang Shen  4  5
Affiliations
  • 1. Department of Orthopedics, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, Anhui Province, China.
  • 2. Department of Orthopedics and Spine Surgery, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, Anhui Province, China.
  • 3. Department of Orthopedics, The First People's Hospital of Hefei, No. 390 Huaihe Road, Hefei, Anhui Province, China.
  • 4. Department of Orthopedics and Spine Surgery, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, Anhui Province, China. [email protected].
  • 5. Laboratory of Spinal and Spinal Cord Injury Regeneration and Repair, The First Affiliated Hospital of Anhui Medical University, Shushan District of Hefei, No. 218 Jixi Road, Anhui Province, China. [email protected].
PMID: 39992585 DOI: 10.1007/s12035-025-04755-2
Abstract

Spinal Cord Injury (SCI) can cause irreversible trauma to nervous tissue, leading to permanent damage to the patient's motor and sensory functions. Extracellular vesicles derived from mesenchymal stem cells (MSC-EVs) can simulate most of the functions of MSCs and are considered an ideal treatment option for SCI. However, the potential mechanism of MSC-EVs treatment for SCI still needs to be explored. We cultured neurons in vitro to investigate the effect of miR-124 on the p62-Keap1-Nrf2 pathway. Besides, MSC-EVs containing miR-124 were injected into a rat Spinal Cord Injury model to observe their neural repair effect. The accumulation of p62 can be reversed by miR-124, which promotes Autophagy and alleviates oxidative stress, thereby exerting neuroprotective effects. Rats who received injection of MSC-EVs overexpressing miR-124 after surgery showed higher BBB scores, lower levels of cell Apoptosis, and better spinal cord tissue morphology. Our results indicated that miR-124 can stabilize the p62-Keap1-Nrf2 loop, thereby promoting Autophagy and alleviating oxidative stress to exert neuroprotective effects. Our research proposes a novel potential target for treating SCI.

Keywords
Extracellular vesicles; Mesenchymal stem cells; MiR-124; P62-Keap1-Nrf2; Spinal cord injury.