Exploring the local immunomodulation of Spinal cord injury using Nanomedicines
(2026)
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- Abstract
- Spinal cord injury (SCI) is a severe public health problem that often leads to permanent sensory, motor, and autonomic dysfunction. Mesenchymal stem cell (MSC) therapy has shown promise for treating SCI, but its therapeutic efficacy is greatly limited by poor cell survival caused by excessive neuroinflammation and immune rejection in the injured microenvironment. After SCI, proinflammatory M1-like microglia dominate, while their transition to pro-resolutive M2-like phenotypes is impaired, driving chronic inflammation. Selective depletion of M1-like microglia can promote inflammation resolution and tissue repair. Colony-stimulating factor 1 receptor (CSF1R) is essential for microglial survival, making it an attractive target for regulating neuroinflammation. This thesis develops CSF1R-based nanomedicine strategies, including PLGA nanoparticles loaded with the CSF1R antagonist PLX5622 and lipid nanoparticles delivering CSF1R-targeting siRNA, to modulate or deplete microglia after SCI. Local administration of CSF1R nanomedicine reduces neuroinflammation and shifts microglia toward a pro-resolutive phenotype, creating a favorable microenvironment for repair. Furthermore, combining CSF1R nanomedicine pretreatment with hyaluronic acid hydrogel–based MSC transplantation significantly improves stem cell survival and enhances functional recovery. Overall, this work demonstrates that nanomedicine-mediated microenvironmental modulation synergizes with stem cell therapy and represents a promising therapeutic strategy for spinal cord injury.
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Citations
Yang, J. (2026). Exploring the local immunomodulation of Spinal cord injury using Nanomedicines. https://hdl.handle.net/2078.5/273115