Agrin‐Enriched Neonatal Spinal Cord‐Derived Extracellular Vesicles Bypass Age Barriers to Organize Spinal Cord Repair
6 affiliations
- 1Xijing Hospital, Fourth Military Medical University
- 2The First Affiliated Hospital of Chongqing Medical University
- 3the University of Hong Kong
- 4Shaanxi University of Chinese Medicine
- 5The Second Affiliated Hospital of Xi'an Jiao Tong University
- 6General Hospital of Northern Theater Command
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.
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BibTeX
@article{zhang2026agrinenriched,
title = {{Agrin‐Enriched Neonatal Spinal Cord‐Derived Extracellular Vesicles Bypass Age Barriers to Organize Spinal Cord Repair}},
author = {Yongfeng Zhang and Qi Liu and Beibei Yu and Borui Xue and Shijie Yang and Teng Ma and Lingli Guo and Haining Wu and Xue Gao and Shengyou Li and Yujie Yang and Yiming Hao and Ziqing Zhu and Meijia Su and Hongyu Li and Shuanshuan Fan and Jiaqi Wang and Huangtao Chen and Longhui Fu and Anhui Qin and Zhenguo Wang and Shihao Nie and Mingze Qin and Xinxin Bai and Guang Kong and Rui Zhao and Dong Lei and Yue Yu and Junxiong Ma and Shouping Gong and Bing Xia and Jinghui Huang},
journal = {Journal of extracellular vesicles},
year = {2026},
month = oct,
doi = {10.1002/jev2.70371},
url = {https://europepmc.org/article/PMC/PMC13653649},
note = {CC BY},
}
RIS
TY - JOUR
TI - Agrin‐Enriched Neonatal Spinal Cord‐Derived Extracellular Vesicles Bypass Age Barriers to Organize Spinal Cord Repair
AU - Yongfeng Zhang
AU - Qi Liu
AU - Beibei Yu
AU - Borui Xue
AU - Shijie Yang
AU - Teng Ma
AU - Lingli Guo
AU - Haining Wu
AU - Xue Gao
AU - Shengyou Li
AU - Yujie Yang
AU - Yiming Hao
AU - Ziqing Zhu
AU - Meijia Su
AU - Hongyu Li
AU - Shuanshuan Fan
AU - Jiaqi Wang
AU - Huangtao Chen
AU - Longhui Fu
AU - Anhui Qin
AU - Zhenguo Wang
AU - Shihao Nie
AU - Mingze Qin
AU - Xinxin Bai
AU - Guang Kong
AU - Rui Zhao
AU - Dong Lei
AU - Yue Yu
AU - Junxiong Ma
AU - Shouping Gong
AU - Bing Xia
AU - Jinghui Huang
PY - 2026
DA - 2026/10/01
JO - Journal of extracellular vesicles
DO - 10.1002/jev2.70371
UR - https://europepmc.org/article/PMC/PMC13653649
AB - 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.
SN - 2001-3078
ER -