Autophagy modulation by hADSCs and green light therapy alleviates inflammation and promotes functional recovery after spinal cord injury.

Background: Spinal cord injury (SCI) results in chronic motor deficits and intractable neuropathic pain, driven by neuroinflammation and impaired tissue repair. Current therapies inadequately address these multifaceted challenges. This study investigated the therapeutic effects of human adipose-derived mesenchymal stem cells (hADSCs) transplantation combined with green light (GL) therapy to modulate inflammation, enhance autophagy, and facilitate functional restoration post-SCI.

Methods: In a murine SCI model, hADSCs (1 × 10 cells) were intraspinally delivered with concurrent GL irradiation (100 lux, 8 h/d). Behavioral assessments included footprint analysis, von Frey test, and thermal hyperalgesia testing. Histological analyses included Luxol Fast Blue (LFB), Nissl, Masson, and hematoxylin and eosin (HE) staining for myelin integrity, neuronal survival and glial scar area. Immunofluorescence, ELISA and qPCR were used to assess inflammation, and autophagy-related proteins were analyzed using immunofluorescence and western blotting. The role of microglial autophagy was investigated by inhibiting autophagy using 3-methyladenine (3MA).

Results: The combined treatment group (hADSCs + GL) showed significant motor function recovery, pain relief, and histological improvement, outperforming either treatment alone. Histological analyses revealed enhanced myelin preservation, reduced glial scar formation, and increased neuronal survival. Quantitative analysis revealed that TNF-α, IL-1β, and CD68 expression in the combined treatment group were markedly lower than those in single-treatment cohorts (P < 0.05). Furthermore, the combined treatment promoted microglia autophagy, evidenced by increased Beclin1 and LC3B expression and decreased P62 in microglia. Inhibition of autophagy with 3MA reversed the anti-inflammatory benefits of the combined therapy, exacerbating the inflammatory response.

Conclusions: The combined treatment of hADSCs transplantation and GL therapy significantly improves functional recovery and reduces inflammation following SCI. The therapeutic effects are mediated in part by the modulation of microglial autophagy.