Transplantation of A2 type astrocytes promotes neural repair and remyelination after spinal cord injury
Abstract Background Limited progress in terms of an effective treatment for spinal cord injury (SCI) emphasizes the urgent need for novel therapies. As a vital central nervous system component, the resident astrocytes play crucial roles in regulating recovery after SCI. In this study, recovery after...
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| Format: | Article |
| Language: | English |
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BMC
2023-02-01
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| Series: | Cell Communication and Signaling |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12964-022-01036-6 |
| _version_ | 1797863993251987456 |
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| author | Jie Chang Zhanyang Qian Binyu Wang Jiang Cao Sheng Zhang Fan Jiang Renyi Kong Xiao Yu Xiaojian Cao Lei Yang Hongtao Chen |
| author_facet | Jie Chang Zhanyang Qian Binyu Wang Jiang Cao Sheng Zhang Fan Jiang Renyi Kong Xiao Yu Xiaojian Cao Lei Yang Hongtao Chen |
| author_sort | Jie Chang |
| collection | DOAJ |
| description | Abstract Background Limited progress in terms of an effective treatment for spinal cord injury (SCI) emphasizes the urgent need for novel therapies. As a vital central nervous system component, the resident astrocytes play crucial roles in regulating recovery after SCI. In this study, recovery after SCI was compared following the transplantation of either A1 or A2 astrocytes. A1 astrocytes are harmful as they upregulate the neurotoxic classical complement cascade genes. Conversely, A2 astrocytes are characterized as neuroprotective as they upregulate the production of many neurotrophic factors. Methods We used different supernatant obtained from microglia stimulated with lipopolysaccharide or interleukin-4 to generate A1 and A2 astrocytes. We detected the influence of astrocytes on neurons by co-culturing A1 and A2 astrocytes with neurons. We transplanted astrocytes into the lesion site of the spinal cord and assessed lesion progression, neural restoration, glia formation and locomotor recovery. Results Astrocytes were polarized into A1 and A2 phenotypes following culture in the supernatant obtained from microglia stimulated with lipopolysaccharide or interleukin-4, respectively. Furthermore, co-culturing A2 astrocytes with neurons significantly suppressed glutamate-induced neuronal apoptosis and promoted the degree of neuron arborization. Transplantation of these A2 astrocytes into the lesion site of the spinal cord of mice significantly improved motor function recovery, preserved spared supraspinal pathways, decreased glia scar deposition, and increased neurofilament formation at the site of injury compared to the transplantation of A1 astrocytes. Additionally, enhanced A2 astrocytes with potentially beneficial A2-like genes were also detected in the A2 group. Moreover, luxol fast blue staining and electron microscopy indicated increased preservation of myelin with organized structure after transplantation of A2 astrocytes than of A1 astrocytes. Conclusions A2 astrocyte transplantation could be a promising potential therapy for SCI. Graphical Abstract Video abstract |
| first_indexed | 2024-04-09T22:45:29Z |
| format | Article |
| id | doaj.art-069c1d64cba04f9195117fd1ddd6da18 |
| institution | Directory Open Access Journal |
| issn | 1478-811X |
| language | English |
| last_indexed | 2024-04-09T22:45:29Z |
| publishDate | 2023-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Communication and Signaling |
| spelling | doaj.art-069c1d64cba04f9195117fd1ddd6da182023-03-22T11:53:01ZengBMCCell Communication and Signaling1478-811X2023-02-0121112010.1186/s12964-022-01036-6Transplantation of A2 type astrocytes promotes neural repair and remyelination after spinal cord injuryJie Chang0Zhanyang Qian1Binyu Wang2Jiang Cao3Sheng Zhang4Fan Jiang5Renyi Kong6Xiao Yu7Xiaojian Cao8Lei Yang9Hongtao Chen10Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical SchoolSpine Center, Zhongda Hospital of Southeast UniversityDepartment of Orthopedics, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Orthopedics, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Orthopedics, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Orthopedics, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Orthopedics, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Orthopedics, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Orthopedics, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Orthopedics, Taizhou People’s Hospital, Nanjing Medical UniversityDepartment of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical SchoolAbstract Background Limited progress in terms of an effective treatment for spinal cord injury (SCI) emphasizes the urgent need for novel therapies. As a vital central nervous system component, the resident astrocytes play crucial roles in regulating recovery after SCI. In this study, recovery after SCI was compared following the transplantation of either A1 or A2 astrocytes. A1 astrocytes are harmful as they upregulate the neurotoxic classical complement cascade genes. Conversely, A2 astrocytes are characterized as neuroprotective as they upregulate the production of many neurotrophic factors. Methods We used different supernatant obtained from microglia stimulated with lipopolysaccharide or interleukin-4 to generate A1 and A2 astrocytes. We detected the influence of astrocytes on neurons by co-culturing A1 and A2 astrocytes with neurons. We transplanted astrocytes into the lesion site of the spinal cord and assessed lesion progression, neural restoration, glia formation and locomotor recovery. Results Astrocytes were polarized into A1 and A2 phenotypes following culture in the supernatant obtained from microglia stimulated with lipopolysaccharide or interleukin-4, respectively. Furthermore, co-culturing A2 astrocytes with neurons significantly suppressed glutamate-induced neuronal apoptosis and promoted the degree of neuron arborization. Transplantation of these A2 astrocytes into the lesion site of the spinal cord of mice significantly improved motor function recovery, preserved spared supraspinal pathways, decreased glia scar deposition, and increased neurofilament formation at the site of injury compared to the transplantation of A1 astrocytes. Additionally, enhanced A2 astrocytes with potentially beneficial A2-like genes were also detected in the A2 group. Moreover, luxol fast blue staining and electron microscopy indicated increased preservation of myelin with organized structure after transplantation of A2 astrocytes than of A1 astrocytes. Conclusions A2 astrocyte transplantation could be a promising potential therapy for SCI. Graphical Abstract Video abstracthttps://doi.org/10.1186/s12964-022-01036-6A2 astrocyteNeural repairRemyelinationSpinal cord injury |
| spellingShingle | Jie Chang Zhanyang Qian Binyu Wang Jiang Cao Sheng Zhang Fan Jiang Renyi Kong Xiao Yu Xiaojian Cao Lei Yang Hongtao Chen Transplantation of A2 type astrocytes promotes neural repair and remyelination after spinal cord injury Cell Communication and Signaling A2 astrocyte Neural repair Remyelination Spinal cord injury |
| title | Transplantation of A2 type astrocytes promotes neural repair and remyelination after spinal cord injury |
| title_full | Transplantation of A2 type astrocytes promotes neural repair and remyelination after spinal cord injury |
| title_fullStr | Transplantation of A2 type astrocytes promotes neural repair and remyelination after spinal cord injury |
| title_full_unstemmed | Transplantation of A2 type astrocytes promotes neural repair and remyelination after spinal cord injury |
| title_short | Transplantation of A2 type astrocytes promotes neural repair and remyelination after spinal cord injury |
| title_sort | transplantation of a2 type astrocytes promotes neural repair and remyelination after spinal cord injury |
| topic | A2 astrocyte Neural repair Remyelination Spinal cord injury |
| url | https://doi.org/10.1186/s12964-022-01036-6 |
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