Autophagy modulation by hADSCs and green light therapy alleviates inflammation and promotes functional recovery after spinal cord injury
Abstract 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 adip...
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BMC
2025-05-01
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| Series: | Stem Cell Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13287-025-04367-6 |
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| author | Junjie Chen Quanxin He Huan Xie Bin Gu Liyi Zhou Daoyuan Jiang Hongxin Xie Li Liang Zhilai Zhou Hui Zhang |
| author_facet | Junjie Chen Quanxin He Huan Xie Bin Gu Liyi Zhou Daoyuan Jiang Hongxin Xie Li Liang Zhilai Zhou Hui Zhang |
| author_sort | Junjie Chen |
| collection | DOAJ |
| description | Abstract 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 × 106 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. |
| format | Article |
| id | doaj-art-ee140650fdae442096c3527d5fececf4 |
| institution | DOAJ |
| issn | 1757-6512 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj-art-ee140650fdae442096c3527d5fececf42025-08-20T03:08:40ZengBMCStem Cell Research & Therapy1757-65122025-05-0116111710.1186/s13287-025-04367-6Autophagy modulation by hADSCs and green light therapy alleviates inflammation and promotes functional recovery after spinal cord injuryJunjie Chen0Quanxin He1Huan Xie2Bin Gu3Liyi Zhou4Daoyuan Jiang5Hongxin Xie6Li Liang7Zhilai Zhou8Hui Zhang9The Affiliated Guangdong Second Provincial General Hospital of Jinan UniversityThe Affiliated Guangdong Second Provincial General Hospital of Jinan UniversityThe Affiliated Guangdong Second Provincial General Hospital of Jinan UniversityThe Affiliated Guangdong Second Provincial General Hospital of Jinan UniversityThe Affiliated Guangdong Second Provincial General Hospital of Jinan UniversityThe Affiliated Guangdong Second Provincial General Hospital of Jinan UniversityThe Second School of Clinical Medicine, Southern Medical UniversityThe Second School of Clinical Medicine, Southern Medical UniversityThe Affiliated Guangdong Second Provincial General Hospital of Jinan UniversityThe Affiliated Guangdong Second Provincial General Hospital of Jinan UniversityAbstract 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 × 106 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.https://doi.org/10.1186/s13287-025-04367-6Spinal cord injuryNeuropathic painGreen lightAdipose-derived mesenchymal stem cellsAutophagy |
| spellingShingle | Junjie Chen Quanxin He Huan Xie Bin Gu Liyi Zhou Daoyuan Jiang Hongxin Xie Li Liang Zhilai Zhou Hui Zhang Autophagy modulation by hADSCs and green light therapy alleviates inflammation and promotes functional recovery after spinal cord injury Stem Cell Research & Therapy Spinal cord injury Neuropathic pain Green light Adipose-derived mesenchymal stem cells Autophagy |
| title | Autophagy modulation by hADSCs and green light therapy alleviates inflammation and promotes functional recovery after spinal cord injury |
| title_full | Autophagy modulation by hADSCs and green light therapy alleviates inflammation and promotes functional recovery after spinal cord injury |
| title_fullStr | Autophagy modulation by hADSCs and green light therapy alleviates inflammation and promotes functional recovery after spinal cord injury |
| title_full_unstemmed | Autophagy modulation by hADSCs and green light therapy alleviates inflammation and promotes functional recovery after spinal cord injury |
| title_short | Autophagy modulation by hADSCs and green light therapy alleviates inflammation and promotes functional recovery after spinal cord injury |
| title_sort | autophagy modulation by hadscs and green light therapy alleviates inflammation and promotes functional recovery after spinal cord injury |
| topic | Spinal cord injury Neuropathic pain Green light Adipose-derived mesenchymal stem cells Autophagy |
| url | https://doi.org/10.1186/s13287-025-04367-6 |
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