Agrin‐Enriched Neonatal Spinal Cord‐Derived Extracellular Vesicles Bypass Age Barriers to Organize Spinal Cord Repair
Year: 2026
Type: article
Abstract: Spinal cord injury (SCI) poses a formidable challenge in regenerative medicine, with current therapeutic strategies proving largely unsuccessful in achieving functional repair. Notably, paediatric patients and neonatal mice exhibit spontaneous and efficient regeneration after SCI, while the mechanisms remain elusive. Through integrated multi-omics analysis in neonatal, adult and aged mice with SCI, we discovered that the regeneration time window, inflammatory response, and intercellular communication are all age-dependent. Neonatal spinal cord-derived extracellular vesicles (nSC-EVs) were identified carrying a regenerative protein signature and were critical mediators in restoring SCI repair in neonatal mice. Functionally, nSC-EVs promote neurogenesis via the Wnt/β-catenin pathway and mediate axonal growth through the core effector Agrin (encoded by Agrn), which was found to be predominantly expressed in endothelial cells. We further developed a targeted delivery system for nSC-EVs, which significantly enhanced functional recovery, including motor and bladder control, in adult SCI mice. This work elucidates the mechanistic basis of age-dependent repair processes and proposes a novel EV-based therapy for SCI.
DOI: 10.1002/jev2.70371
Authors: Yongfeng Zhang, Qi Liu, Beibei Yu, Borui Xue, Shijie Yang, Teng Ma, Lingli Guo, Haining Wu, Xue Gao, Shengyou Li, Yujie Yang, Yiming Hao, Ziqing Zhu, Meijia Su, Hongyu Li, Shuanshuan Fan, Jiaqi Wang, Huangtao Chen, Longhui Fu, Anhui Qin, Zhenguo Wang, Shihao Nie, Mingze Qin, Xinxin Bai, Guang Kong, Rui Zhao, Dong Lei, Yue Yu, Junxiong Ma, Shouping Gong, Bing Xia, Jinghui Huang
Institutions: First Affiliated Hospital of Xi'an Jiaotong University, Xijing Hospital, Xi'an Jiaotong University, Air Force Medical University, The Affiliated Yongchuan Hospital of Chongqing Medical University, University of Hong Kong, Shaanxi University of Chinese Medicine, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an Medical University
Language: English
Topic: Spinal Cord Injury Research
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,410
OpenAlex ID: W7221319884