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.