The Combination of Sodium Tanshinone IIA Sulfonate and Mesenchymal Stem Cell-derived Exosomes Against Spinal Cord Injury via VEGF Pathway

Spinal cord injury (SCI), a prevalent cause of severe disability, primarily stems from trauma, degenerative pathologies, or underlying diseases. Spinal cord injury presents significant therapeutic challenges. This study investigated the potential synergistic effect of combining Sodium Tanshinone IIA Sulfonate (STS) and bone mesenchymal stem cell-derived exosomes (BMSC-Exos) for SCI treatment, focusing on the vascular endothelial growth factor (VEGF) pathway.The STS-Exo combination significantly protected Mouse Brain Microvascular Endothelial Cells (bEnd.3) against H₂O₂-induced cytotoxicity, as shown by CCK-8. This synergistic treatment robustly enhanced angiogenic capacity measured through tube formation analysis and accelerated endothelial cell migration in scratch wound healing assays, outperforming individual monotherapies. In SCI rats, combined therapy promoted functional recovery, evidenced by elevated BBB locomotor scores and footprint analysis. Histopathological assessment via HE staining revealed attenuated tissue damage, while Evans Blue extravasation tests confirmed restoration of blood-spinal cord barrier(BSCB) integrity. Furthermore, immunofluorescence quantification showed marked reduction in glial scar formation. Mechanistically, WB and IF analyses confirmed that the STS-Exo combination potently activated the VEGF signaling pathway. This combination strategy represents a promising therapeutic approach for SCI.