Adipose-derived stem cells modulate neuroinflammation and improve functional recovery in chronic constriction injury of the rat sciatic nerve
IntroductionCompressive neuropathy, a common chronic traumatic injury of peripheral nerves, leads to variable impairment in sensory and motor function. Clinical symptoms persist in a significant portion of patients despite decompression, with muscle atrophy and persistent neuropathic pain affecting...
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Frontiers Media S.A.
2023-06-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2023.1172740/full |
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| author | Szu-Han Chen Szu-Han Chen Szu-Han Chen Szu-Han Chen Chia-Ching Wu Chia-Ching Wu Wan-Ling Tseng Wan-Ling Tseng Fu-I Lu Fu-I Lu Ya-Hsin Liu Shau-Ping Lin Sheng-Che Lin Yuan-Yu Hsueh Yuan-Yu Hsueh Yuan-Yu Hsueh Yuan-Yu Hsueh |
| author_facet | Szu-Han Chen Szu-Han Chen Szu-Han Chen Szu-Han Chen Chia-Ching Wu Chia-Ching Wu Wan-Ling Tseng Wan-Ling Tseng Fu-I Lu Fu-I Lu Ya-Hsin Liu Shau-Ping Lin Sheng-Che Lin Yuan-Yu Hsueh Yuan-Yu Hsueh Yuan-Yu Hsueh Yuan-Yu Hsueh |
| author_sort | Szu-Han Chen |
| collection | DOAJ |
| description | IntroductionCompressive neuropathy, a common chronic traumatic injury of peripheral nerves, leads to variable impairment in sensory and motor function. Clinical symptoms persist in a significant portion of patients despite decompression, with muscle atrophy and persistent neuropathic pain affecting 10%–25% of cases. Excessive inflammation and immune cell infiltration in the injured nerve hinder axon regeneration and functional recovery. Although adipose-derived stem cells (ASCs) have demonstrated neural regeneration and immunomodulatory potential, their specific effects on compressive neuropathy are still unclear.MethodsWe conducted modified CCI models on adult male Sprague-Dawley rats to induce irreversible neuropathic pain and muscle atrophy in the sciatic nerve. Intraneural ASC injection and nerve decompression were performed. Behavioral analysis, muscle examination, electrophysiological evaluation, and immunofluorescent examination of the injured nerve and associated DRG were conducted to explore axon regeneration, neuroinflammation, and the modulation of inflammatory gene expression. Transplanted ASCs were tracked to investigate potential beneficial mechanisms on the local nerve and DRG.ResultsPersistent neuropathic pain was induced by chronic constriction of the rat sciatic nerve. Local ASC treatment has demonstrated robust beneficial outcomes, including the alleviation of mechanical allodynia, improvement of gait, regeneration of muscle fibers, and electrophysiological recovery. In addition, locally transplanted ASCs facilitated axon remyelination, alleviated neuroinflammation, and reduced inflammatory cell infiltration of the injured nerve and associated dorsal root ganglion (DRG). Trafficking of the transplanted ASC preserved viability and phenotype less than 7 days but contributed to robust immunomodulatory regulation of inflammatory gene expression in both the injured nerve and DRG.DiscussionLocally transplanted ASC on compressed nerve improve sensory and motor recoveries from irreversible chronic constriction injury of rat sciatic nerve via alleviation of both local and remote neuroinflammation, suggesting the promising role of adjuvant ASC therapies for clinical compressive neuropathy. |
| first_indexed | 2024-03-13T02:31:37Z |
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| id | doaj.art-ea77edd4106d4d8d9b48d5ab0d15bf56 |
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| language | English |
| last_indexed | 2024-03-13T02:31:37Z |
| publishDate | 2023-06-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Neuroscience |
| spelling | doaj.art-ea77edd4106d4d8d9b48d5ab0d15bf562023-06-29T16:38:29ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2023-06-011710.3389/fnins.2023.11727401172740Adipose-derived stem cells modulate neuroinflammation and improve functional recovery in chronic constriction injury of the rat sciatic nerveSzu-Han Chen0Szu-Han Chen1Szu-Han Chen2Szu-Han Chen3Chia-Ching Wu4Chia-Ching Wu5Wan-Ling Tseng6Wan-Ling Tseng7Fu-I Lu8Fu-I Lu9Ya-Hsin Liu10Shau-Ping Lin11Sheng-Che Lin12Yuan-Yu Hsueh13Yuan-Yu Hsueh14Yuan-Yu Hsueh15Yuan-Yu Hsueh16Division of Plastic and Reconstructive Surgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, TaiwanCenter of Cell Therapy, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, TaiwanInternational Research Center for Wound Repair and Regeneration, National Cheng Kung University, Tainan, TaiwanInstitute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, TaiwanInternational Research Center for Wound Repair and Regeneration, National Cheng Kung University, Tainan, TaiwanDepartment of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan, TaiwanDivision of Plastic and Reconstructive Surgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, TaiwanInstitute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, TaiwanDepartment of Biotechnology and Bioindustry Science, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, TaiwanThe integrative Evolutionary Galliform Genomics (iEGG) and Animal Biotechnology Center, National Chung Hsing University, Taichung, TaiwanDepartment of Life Sciences, National Cheng Kung University, Tainan, TaiwanInstitute of Biotechnology, College of Bio-Resources and Agriculture, National Taiwan University, Taipei, Taiwan0Division of Plastic Surgery, Department of Surgery, An-Nan Hospital, China Medical University, Tainan, TaiwanDivision of Plastic and Reconstructive Surgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, TaiwanCenter of Cell Therapy, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, TaiwanInternational Research Center for Wound Repair and Regeneration, National Cheng Kung University, Tainan, TaiwanInstitute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, TaiwanIntroductionCompressive neuropathy, a common chronic traumatic injury of peripheral nerves, leads to variable impairment in sensory and motor function. Clinical symptoms persist in a significant portion of patients despite decompression, with muscle atrophy and persistent neuropathic pain affecting 10%–25% of cases. Excessive inflammation and immune cell infiltration in the injured nerve hinder axon regeneration and functional recovery. Although adipose-derived stem cells (ASCs) have demonstrated neural regeneration and immunomodulatory potential, their specific effects on compressive neuropathy are still unclear.MethodsWe conducted modified CCI models on adult male Sprague-Dawley rats to induce irreversible neuropathic pain and muscle atrophy in the sciatic nerve. Intraneural ASC injection and nerve decompression were performed. Behavioral analysis, muscle examination, electrophysiological evaluation, and immunofluorescent examination of the injured nerve and associated DRG were conducted to explore axon regeneration, neuroinflammation, and the modulation of inflammatory gene expression. Transplanted ASCs were tracked to investigate potential beneficial mechanisms on the local nerve and DRG.ResultsPersistent neuropathic pain was induced by chronic constriction of the rat sciatic nerve. Local ASC treatment has demonstrated robust beneficial outcomes, including the alleviation of mechanical allodynia, improvement of gait, regeneration of muscle fibers, and electrophysiological recovery. In addition, locally transplanted ASCs facilitated axon remyelination, alleviated neuroinflammation, and reduced inflammatory cell infiltration of the injured nerve and associated dorsal root ganglion (DRG). Trafficking of the transplanted ASC preserved viability and phenotype less than 7 days but contributed to robust immunomodulatory regulation of inflammatory gene expression in both the injured nerve and DRG.DiscussionLocally transplanted ASC on compressed nerve improve sensory and motor recoveries from irreversible chronic constriction injury of rat sciatic nerve via alleviation of both local and remote neuroinflammation, suggesting the promising role of adjuvant ASC therapies for clinical compressive neuropathy.https://www.frontiersin.org/articles/10.3389/fnins.2023.1172740/fulladipose derived stem cellsneuroinflammationcompressive neuropathychronic constriction injuryneuropathic painstem cell therapy |
| spellingShingle | Szu-Han Chen Szu-Han Chen Szu-Han Chen Szu-Han Chen Chia-Ching Wu Chia-Ching Wu Wan-Ling Tseng Wan-Ling Tseng Fu-I Lu Fu-I Lu Ya-Hsin Liu Shau-Ping Lin Sheng-Che Lin Yuan-Yu Hsueh Yuan-Yu Hsueh Yuan-Yu Hsueh Yuan-Yu Hsueh Adipose-derived stem cells modulate neuroinflammation and improve functional recovery in chronic constriction injury of the rat sciatic nerve Frontiers in Neuroscience adipose derived stem cells neuroinflammation compressive neuropathy chronic constriction injury neuropathic pain stem cell therapy |
| title | Adipose-derived stem cells modulate neuroinflammation and improve functional recovery in chronic constriction injury of the rat sciatic nerve |
| title_full | Adipose-derived stem cells modulate neuroinflammation and improve functional recovery in chronic constriction injury of the rat sciatic nerve |
| title_fullStr | Adipose-derived stem cells modulate neuroinflammation and improve functional recovery in chronic constriction injury of the rat sciatic nerve |
| title_full_unstemmed | Adipose-derived stem cells modulate neuroinflammation and improve functional recovery in chronic constriction injury of the rat sciatic nerve |
| title_short | Adipose-derived stem cells modulate neuroinflammation and improve functional recovery in chronic constriction injury of the rat sciatic nerve |
| title_sort | adipose derived stem cells modulate neuroinflammation and improve functional recovery in chronic constriction injury of the rat sciatic nerve |
| topic | adipose derived stem cells neuroinflammation compressive neuropathy chronic constriction injury neuropathic pain stem cell therapy |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2023.1172740/full |
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