Frontiers in Cell and Developmental Biology (Nov 2021)
Bone Marrow Mesenchymal Stem Cell-Derived Exosomes Accelerate Functional Recovery After Spinal Cord Injury by Promoting the Phagocytosis of Macrophages to Clean Myelin Debris
- 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
Affiliations
- Xiaolong Sheng
- Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, China
- Xiaolong Sheng
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, China
- Xiaolong Sheng
- Hunan Engineering Research Center of Sports and Health, Changsha, China
- Xiaolong Sheng
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
- Jinyun Zhao
- Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, China
- Jinyun Zhao
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, China
- Jinyun Zhao
- Hunan Engineering Research Center of Sports and Health, Changsha, China
- Jinyun Zhao
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
- Miao Li
- Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, China
- Miao Li
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, China
- Miao Li
- Hunan Engineering Research Center of Sports and Health, Changsha, China
- Miao Li
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
- Miao Li
- Department of Orthopedics, Hunan Children’s Hospital, Changsha, China
- Yan Xu
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, China
- Yan Xu
- Hunan Engineering Research Center of Sports and Health, Changsha, China
- Yan Xu
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
- Yan Xu
- Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, China
- Yi Zhou
- Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, China
- Yi Zhou
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, China
- Yi Zhou
- Hunan Engineering Research Center of Sports and Health, Changsha, China
- Yi Zhou
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
- Yi Zhou
- Department of Pain, Institute of Pain Medicine, Third Xiangya Hospital of Central South University, Changsha, China
- Jiaqi Xu
- Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, China
- Jiaqi Xu
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, China
- Jiaqi Xu
- Hunan Engineering Research Center of Sports and Health, Changsha, China
- Jiaqi Xu
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
- Rundong He
- Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, China
- Rundong He
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, China
- Rundong He
- Hunan Engineering Research Center of Sports and Health, Changsha, China
- Rundong He
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
- Hongbin Lu
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, China
- Hongbin Lu
- Hunan Engineering Research Center of Sports and Health, Changsha, China
- Hongbin Lu
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
- Hongbin Lu
- Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, China
- Tianding Wu
- Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, China
- Tianding Wu
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, China
- Tianding Wu
- Hunan Engineering Research Center of Sports and Health, Changsha, China
- Tianding Wu
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
- Chunyue Duan
- Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, China
- Chunyue Duan
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, China
- Chunyue Duan
- Hunan Engineering Research Center of Sports and Health, Changsha, China
- Chunyue Duan
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
- Yong Cao
- Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, China
- Yong Cao
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, China
- Yong Cao
- Hunan Engineering Research Center of Sports and Health, Changsha, China
- Yong Cao
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
- Jianzhong Hu
- Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, China
- Jianzhong Hu
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, China
- Jianzhong Hu
- Hunan Engineering Research Center of Sports and Health, Changsha, China
- Jianzhong Hu
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
- DOI
- https://doi.org/10.3389/fcell.2021.772205
- Journal volume & issue
-
Vol. 9
Abstract
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.
Keywords
