2. Academic Validation
  3. Athlete-derived extracellular vesicles protect against spinal cord injury via inhibition of neuronal ferroptosis

Athlete-derived extracellular vesicles protect against spinal cord injury via inhibition of neuronal ferroptosis

  • Sci Adv. 2025 Dec 12;11(50):eadx7695. doi: 10.1126/sciadv.adx7695.
Jiaxing Wang 1 2,  Xuhui Ge 3,  Chuandong Lang 1,  Wenbin Xu 1,  Tao Hu 1,  Liang Wang 1,  Feng Hu 1,  Yongjin Sun 1,  Feng Zhang 1,  Weihua Cai 4,  Wei Liu 3,  Wenzhi Zhang 1,  Yuluo Rong 1 5 6
Affiliations

Affiliations

  • 1 Department of Orthopaedics, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, Anhui, China.
  • 2 Department of Orthopedics, Taizhou School of Clinical Medicine, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou 225300, Jiangsu, China.
  • 3 Department of Orthopedics, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, China.
  • 4 Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu, China.
  • 5 National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai 200444, China.
  • 6 State Key Laboratory of Trauma and Chemical Poisoning, Army Medical University, Chongqing 400038, China.
PMID: 41385620 DOI: 10.1126/sciadv.adx7695
Abstract

Spinal cord injury (SCI) causes high morbidity, disability, and mortality, while current surgical and pharmacological treatments provide limited benefit. Ferroptosis, a newly recognized form of regulated cell death, contributes critically to SCI pathology, and targeting this process may enhance neuronal survival. Extracellular vesicles, key mediators of intercellular communication, are emerging as promising therapeutic agents for central nervous system injury. Here, we examined the role of athlete-derived plasma extracellular vesicles (AEVs) in neuronal Ferroptosis and motor function recovery after SCI. In a murine model, AEVs markedly inhibited Ferroptosis and improved motor outcomes. Mechanistically, AEVs delivered RNF216, which promoted ubiquitination and degradation of NOX1, thereby reducing ferroptotic damage and facilitating recovery. Moreover, RNF216-enriched vesicles enhanced synaptic plasticity, supporting neuronal regeneration and network reestablishment. These findings reveal a previously unrecognized RNF216-NOX1 axis in SCI and highlight AEVs as a previously unidentified therapeutic strategy.

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