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The transplantation of mesenchymal stem cell\u2010derived exosomes has shown great promise. Wnt5a has been reported to promote neuronal differentiation and spinal cord regeneration. However, its mechanistic role when delivered via exosomes remains unclear. In the present study, the function and underlying mechanism of Wnt5a in promoting neuronal differentiation and spinal cord repair were investigated using bone marrow mesenchymal stem cell\u2010derived exosomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study initially constructed Wnt5a\u2010overexpressing BMSCs and isolated and characterized their exosomes. Subsequently, in\u00a0vitro experiments were conducted to detect markers of neurons, astrocytes, and microglia. This was followed by high\u2010throughput sequencing to analyze related pathways. Finally, in\u00a0vivo experiments were performed, in which rats were divided into the Sham group, the SCI group, the Exo group, and the pLV\u2010Exo\u2010Wnt5a group. The effects of exosomes in\u00a0vivo were analyzed through histological, behavioral, electrophysiological, western blot, PCR, and immunofluorescence assays.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our results demonstrated that Wnt5a\u2010enriched BMSC\u2010Exos significantly enhanced the proliferation and neuronal differentiation of neural stem cells, while suppressing astrocyte formation. High\u2010throughput RNA sequencing revealed an association between Wnt5a and the NF\u2010\u03baB signaling pathway. Intervention with lipopolysaccharide confirmed that Wnt5a exerts a suppressive effect on this pathway. In\u00a0vivo, the transplantation of Wnt5a\u2010modified BMSC\u2010Exos facilitated the polarization of microglia towards an anti\u2010inflammatory M2 phenotype, promoted neurogenesis, reduced astrocyte accumulation, improved spinal cord tissue architecture, and led to better motor function recovery.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Collectively, these findings indicate that Wnt5a enhances the neuroregenerative potential of BMSC\u2010Exos by modulating immune responses and suppressing neuroinflammation, likely through inhibiting the NF\u2010\u03baB signaling pathway.<\/jats:p>\n                  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