The SHEDs-derived apoptotic bodies for inflammatory regulation in spinal cord repair

  • NPJ Regen Med. 2026 Apr 23;11(1):30. doi: 10.1038/s41536-026-00475-w.
Lihua Luo  #  1 ,  Na Dong  #  2  3 ,  Junpeng Xu  #  2  3 ,  Chen Zhang  1 ,  Sa Bao  1 ,  Haichao Xu  1 ,  Xiping Wang  1 ,  Peng Dai  3 ,  Caiyan Li  3 ,  Qiao Zhang  2  3 ,  Yibo Ying  2  3 ,  Dawei Jiang  2  3 ,  Shengcun Li  3  4 ,  Ping Wu  2  3 ,  Liqing Mei  1 ,  Xiaokun Li  5  6 ,  Junjie Deng  7  8 ,  Yihuai Pan  9 ,  Zhouguang Wang  10  11
Affiliations
  • 1. School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, China.
  • 2. The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
  • 3. Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision, and Brain Health), National Key Laboratory of Macromolecular Drugs and Large-scale Preparation, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China.
  • 4. Rehabilitation Medicine Center, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
  • 5. The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China. [email protected].
  • 6. Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision, and Brain Health), National Key Laboratory of Macromolecular Drugs and Large-scale Preparation, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China. [email protected].
  • 7. Joint Centre of Translational Medicine, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, China. [email protected].
  • 8. Zhejiang Engineering Research Center for Tissue Repair Materials, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, China. [email protected].
  • 9. School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, China. [email protected].
  • 10. The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China. [email protected].
  • 11. Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision, and Brain Health), National Key Laboratory of Macromolecular Drugs and Large-scale Preparation, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China. [email protected].
  • # Contributed equally.
PMID: 42026088 DOI: 10.1038/s41536-026-00475-w
Abstract

Neuroinflammation is a key therapeutic target for spinal cord injury (SCI). Apoptotic bodies (ABs) derived from mesenchymal stem cells may modulate early inflammation, promoting SCI repair. Stem cells from human exfoliated deciduous teeth (SHEDs), with neural crest origins, are promising for neurological therapies, but their ABs' role in SCI remains unclear. In this study, as exploratory research, we aimed to investigate the preliminary effects and mechanisms of SHEDs-derived ABs on the treatment of SCI. Herein, SHEDs-derived ABs enhanced functional recovery in SCI mice, improving BMS scores, joint movement, and bioelectrical conduction. Histologically, ABs boosted axonal growth and neuronal regeneration. Moreover, SHEDs-derived ABs significantly suppressed M1 polarization while enhancing M2 polarization in both in vitro and in vivo models. GO/KEGG analyses revealed AB enrichment in immune-related pathways. Mechanistically, the ANXA1/FPR2 axis was critical for ABs-induced microglia/macrophage polarization, with M1 regulation mediated by the NF-κB pathway and M2 modulation driven by the Akt/mTOR pathway. Thus, SHEDs-derived ABs may serve as a clinically translatable strategy for treating SCI by mediating immunomodulation via the ANXA1/FPR2 axis.

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