Bone Marrow Mesenchymal Stem Cell-Derived Exosomes Accelerate Functional Recovery After Spinal Cord Injury by Promoting the Phagocytosis of Macrophages to Clean Myelin Debris
Macrophage phagocytosis contributes predominantly to processing central nervous system (CNS) debris and further facilitates neurological function restoration after CNS injury. The aims of this study were to evaluate the effect of bone marrow mesenchymal stem cells (BMSC)-derived exosomes (BMSC-Exos)...
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Frontiers Media S.A.
2021
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oai:doaj.org-article:0349be0512524007844d069fa4adbc392021-11-08T05:33:06ZBone Marrow Mesenchymal Stem Cell-Derived Exosomes Accelerate Functional Recovery After Spinal Cord Injury by Promoting the Phagocytosis of Macrophages to Clean Myelin Debris2296-634X10.3389/fcell.2021.772205https://doaj.org/article/0349be0512524007844d069fa4adbc392021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcell.2021.772205/fullhttps://doaj.org/toc/2296-634XMacrophage phagocytosis contributes predominantly to processing central nervous system (CNS) debris and further facilitates neurological function restoration after CNS injury. The aims of this study were to evaluate the effect of bone marrow mesenchymal stem cells (BMSC)-derived exosomes (BMSC-Exos) on the phagocytic capability of macrophages to clear myelin debris and to investigate the underlying molecular mechanism during the spinal cord injury (SCI) process. This work reveals that monocyte-derived macrophages (MDMs) infiltrating into the SCI site could efficiently engulf myelin debris and process phagocytic material. However, the phagocytic ability of macrophages to clear tissue debris is compromised after SCI. The administration of BMSC-Exos as an approach for SCI treatment could rescue macrophage normal function by improving the phagocytic capability of myelin debris internalization, which is beneficial for SCI repair, as evidenced by better axon regrowth and increased hindlimb locomotor functional recovery in a rodent model. Examination of macrophage treatment with BMSC-Exos revealed that BMSC-Exos could promote the capacity of macrophages to phagocytose myelin debris in vitro and could create a regenerative microenvironment for axon regrowth. In addition, we confirmed that BMSC-Exo treatment resulted in improved phagocytosis of engulfed myelin debris by promoting the expression of macrophage receptor with collagenous structure (MARCO) in macrophages. The inhibition of MARCO with PolyG (a MARCO antagonist) impaired the effect of BMSC-Exos on the phagocytic capacity of macrophages and resulted in compromised myelin clearance at the lesion site, leading to further tissue damage and impaired functional healing after SCI. In conclusion, these data indicated that targeting the phagocytic ability of macrophages may have therapeutic potential for the improvement in functional healing after SCI. The administration of BMSC-Exos as a cell-free immune therapy strategy has wide application prospects for SCI treatment.Xiaolong ShengXiaolong ShengXiaolong ShengXiaolong ShengJinyun ZhaoJinyun ZhaoJinyun ZhaoJinyun ZhaoMiao LiMiao LiMiao LiMiao LiMiao LiYan XuYan XuYan XuYan XuYi ZhouYi ZhouYi ZhouYi ZhouYi ZhouJiaqi XuJiaqi XuJiaqi XuJiaqi XuRundong HeRundong HeRundong HeRundong HeHongbin LuHongbin LuHongbin LuHongbin LuTianding WuTianding WuTianding WuTianding WuChunyue DuanChunyue DuanChunyue DuanChunyue DuanYong CaoYong CaoYong CaoYong CaoJianzhong HuJianzhong HuJianzhong HuJianzhong HuFrontiers Media S.A.articleBMSC derived exosomesmacrophagephagocytosismyelin debrisspinal cord injuryBiology (General)QH301-705.5ENFrontiers in Cell and Developmental Biology, Vol 9 (2021) |
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BMSC derived exosomes macrophage phagocytosis myelin debris spinal cord injury Biology (General) QH301-705.5 |
| spellingShingle |
BMSC derived exosomes macrophage phagocytosis myelin debris spinal cord injury Biology (General) QH301-705.5 Xiaolong Sheng Xiaolong Sheng Xiaolong Sheng Xiaolong Sheng Jinyun Zhao Jinyun Zhao Jinyun Zhao Jinyun Zhao Miao Li Miao Li Miao Li Miao Li Miao Li Yan Xu Yan Xu Yan Xu Yan Xu Yi Zhou Yi Zhou Yi Zhou Yi Zhou Yi Zhou Jiaqi Xu Jiaqi Xu Jiaqi Xu Jiaqi Xu Rundong He Rundong He Rundong He Rundong He Hongbin Lu Hongbin Lu Hongbin Lu Hongbin Lu Tianding Wu Tianding Wu Tianding Wu Tianding Wu Chunyue Duan Chunyue Duan Chunyue Duan Chunyue Duan Yong Cao Yong Cao Yong Cao Yong Cao Jianzhong Hu Jianzhong Hu Jianzhong Hu Jianzhong Hu Bone Marrow Mesenchymal Stem Cell-Derived Exosomes Accelerate Functional Recovery After Spinal Cord Injury by Promoting the Phagocytosis of Macrophages to Clean Myelin Debris |
| description |
Macrophage phagocytosis contributes predominantly to processing central nervous system (CNS) debris and further facilitates neurological function restoration after CNS injury. The aims of this study were to evaluate the effect of bone marrow mesenchymal stem cells (BMSC)-derived exosomes (BMSC-Exos) on the phagocytic capability of macrophages to clear myelin debris and to investigate the underlying molecular mechanism during the spinal cord injury (SCI) process. This work reveals that monocyte-derived macrophages (MDMs) infiltrating into the SCI site could efficiently engulf myelin debris and process phagocytic material. However, the phagocytic ability of macrophages to clear tissue debris is compromised after SCI. The administration of BMSC-Exos as an approach for SCI treatment could rescue macrophage normal function by improving the phagocytic capability of myelin debris internalization, which is beneficial for SCI repair, as evidenced by better axon regrowth and increased hindlimb locomotor functional recovery in a rodent model. Examination of macrophage treatment with BMSC-Exos revealed that BMSC-Exos could promote the capacity of macrophages to phagocytose myelin debris in vitro and could create a regenerative microenvironment for axon regrowth. In addition, we confirmed that BMSC-Exo treatment resulted in improved phagocytosis of engulfed myelin debris by promoting the expression of macrophage receptor with collagenous structure (MARCO) in macrophages. The inhibition of MARCO with PolyG (a MARCO antagonist) impaired the effect of BMSC-Exos on the phagocytic capacity of macrophages and resulted in compromised myelin clearance at the lesion site, leading to further tissue damage and impaired functional healing after SCI. In conclusion, these data indicated that targeting the phagocytic ability of macrophages may have therapeutic potential for the improvement in functional healing after SCI. The administration of BMSC-Exos as a cell-free immune therapy strategy has wide application prospects for SCI treatment. |
| format |
article |
| author |
Xiaolong Sheng Xiaolong Sheng Xiaolong Sheng Xiaolong Sheng Jinyun Zhao Jinyun Zhao Jinyun Zhao Jinyun Zhao Miao Li Miao Li Miao Li Miao Li Miao Li Yan Xu Yan Xu Yan Xu Yan Xu Yi Zhou Yi Zhou Yi Zhou Yi Zhou Yi Zhou Jiaqi Xu Jiaqi Xu Jiaqi Xu Jiaqi Xu Rundong He Rundong He Rundong He Rundong He Hongbin Lu Hongbin Lu Hongbin Lu Hongbin Lu Tianding Wu Tianding Wu Tianding Wu Tianding Wu Chunyue Duan Chunyue Duan Chunyue Duan Chunyue Duan Yong Cao Yong Cao Yong Cao Yong Cao Jianzhong Hu Jianzhong Hu Jianzhong Hu Jianzhong Hu |
| author_facet |
Xiaolong Sheng Xiaolong Sheng Xiaolong Sheng Xiaolong Sheng Jinyun Zhao Jinyun Zhao Jinyun Zhao Jinyun Zhao Miao Li Miao Li Miao Li Miao Li Miao Li Yan Xu Yan Xu Yan Xu Yan Xu Yi Zhou Yi Zhou Yi Zhou Yi Zhou Yi Zhou Jiaqi Xu Jiaqi Xu Jiaqi Xu Jiaqi Xu Rundong He Rundong He Rundong He Rundong He Hongbin Lu Hongbin Lu Hongbin Lu Hongbin Lu Tianding Wu Tianding Wu Tianding Wu Tianding Wu Chunyue Duan Chunyue Duan Chunyue Duan Chunyue Duan Yong Cao Yong Cao Yong Cao Yong Cao Jianzhong Hu Jianzhong Hu Jianzhong Hu Jianzhong Hu |
| author_sort |
Xiaolong Sheng |
| title |
Bone Marrow Mesenchymal Stem Cell-Derived Exosomes Accelerate Functional Recovery After Spinal Cord Injury by Promoting the Phagocytosis of Macrophages to Clean Myelin Debris |
| title_short |
Bone Marrow Mesenchymal Stem Cell-Derived Exosomes Accelerate Functional Recovery After Spinal Cord Injury by Promoting the Phagocytosis of Macrophages to Clean Myelin Debris |
| title_full |
Bone Marrow Mesenchymal Stem Cell-Derived Exosomes Accelerate Functional Recovery After Spinal Cord Injury by Promoting the Phagocytosis of Macrophages to Clean Myelin Debris |
| title_fullStr |
Bone Marrow Mesenchymal Stem Cell-Derived Exosomes Accelerate Functional Recovery After Spinal Cord Injury by Promoting the Phagocytosis of Macrophages to Clean Myelin Debris |
| title_full_unstemmed |
Bone Marrow Mesenchymal Stem Cell-Derived Exosomes Accelerate Functional Recovery After Spinal Cord Injury by Promoting the Phagocytosis of Macrophages to Clean Myelin Debris |
| title_sort |
bone marrow mesenchymal stem cell-derived exosomes accelerate functional recovery after spinal cord injury by promoting the phagocytosis of macrophages to clean myelin debris |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/0349be0512524007844d069fa4adbc39 |
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