Exosomes Derived From Pericytes Improve Microcirculation and Protect Blood–Spinal Cord Barrier After Spinal Cord Injury in Mice
Spinal cord injury (SCI) often leads to severe and permanent paralysis and places a heavy burden on individuals, families, and society. Until now, the therapy of SCI is still a big challenge for the researchers. Transplantation of mesenchymal stem cells (MSCs) is a hot spot for the treatment of SCI,...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-04-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fnins.2019.00319/full |
| _version_ | 1818016768049807360 |
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| author | Xiaochen Yuan Qingbin Wu Peng Wang Yingli Jing Haijiang Yao Yinshan Tang Zhigang Li Honggang Zhang Ruijuan Xiu |
| author_facet | Xiaochen Yuan Qingbin Wu Peng Wang Yingli Jing Haijiang Yao Yinshan Tang Zhigang Li Honggang Zhang Ruijuan Xiu |
| author_sort | Xiaochen Yuan |
| collection | DOAJ |
| description | Spinal cord injury (SCI) often leads to severe and permanent paralysis and places a heavy burden on individuals, families, and society. Until now, the therapy of SCI is still a big challenge for the researchers. Transplantation of mesenchymal stem cells (MSCs) is a hot spot for the treatment of SCI, but many problems and risks have not been resolved. Some studies have reported that the therapeutic effect of MSCs on SCI is related to the paracrine secretion of cells. The exosomes secreted by MSCs have therapeutic potential for many diseases. There are abundant pericytes which possess the characteristics of stem cells in the neurovascular unit. Due to the close relationship between pericytes and endothelial cells, the exosomes of pericytes can be taken up by endothelial cells more easily. There are fewer studies about the therapeutic potential of the exosomes derived from pericytes on SCI now. In this study, exosomes of pericytes were transplanted into the mice with SCI to study the restoration of motor function and explore the underlying mechanism. We found that the exosomes derived from pericytes could reduce pathological changes, improve the motor function, the blood flow and oxygen deficiency after SCI. In addition, the exosomes could improve the endothelial ability to regulate blood flow, protect the blood-spinal cord barrier, reduce edema, decrease the expression of HIF-1α, Bax, Aquaporin-4, and MMP2, increase the expression of Claudin-5, bcl-2 and inhibit apoptosis. The experiments in vitro proved that exosomes derived from pericytes could protect the barrier of spinal cord microvascular endothelial cells under hypoxia condition, which was related to PTEN/AKT pathway. In summary, our study showed that exosomes of pericytes had therapeutic prospects for SCI. |
| first_indexed | 2024-04-14T07:18:13Z |
| format | Article |
| id | doaj.art-c453e061dea240f89062814c5800fd39 |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-04-14T07:18:13Z |
| publishDate | 2019-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-c453e061dea240f89062814c5800fd392022-12-22T02:06:15ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2019-04-011310.3389/fnins.2019.00319448861Exosomes Derived From Pericytes Improve Microcirculation and Protect Blood–Spinal Cord Barrier After Spinal Cord Injury in MiceXiaochen Yuan0Qingbin Wu1Peng Wang2Yingli Jing3Haijiang Yao4Yinshan Tang5Zhigang Li6Honggang Zhang7Ruijuan Xiu8Key Laboratory of Microcirculation, Ministry of Health, Institute of Microcirculation, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, ChinaKey Laboratory of Microcirculation, Ministry of Health, Institute of Microcirculation, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, ChinaOrthopedics Department, Hebei Provincial Hospital of Traditional Chinese Medicine, Shijiazhuang, ChinaChina Rehabilitation Science Institute, China Rehabilitation Research Center, Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing Key Laboratory of Neural Injury and Rehabilitation, Beijing, ChinaTreatment Center of TCM, Beijing Bo’ai Hospital, China Rehabilitation Research Center, School of Rehabilitation, Capital Medical University, Beijing, ChinaDepartment of Rehabilitation in Traditional Chinese Medicine, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaSchool of Acupuncture, Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, ChinaKey Laboratory of Microcirculation, Ministry of Health, Institute of Microcirculation, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, ChinaKey Laboratory of Microcirculation, Ministry of Health, Institute of Microcirculation, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, ChinaSpinal cord injury (SCI) often leads to severe and permanent paralysis and places a heavy burden on individuals, families, and society. Until now, the therapy of SCI is still a big challenge for the researchers. Transplantation of mesenchymal stem cells (MSCs) is a hot spot for the treatment of SCI, but many problems and risks have not been resolved. Some studies have reported that the therapeutic effect of MSCs on SCI is related to the paracrine secretion of cells. The exosomes secreted by MSCs have therapeutic potential for many diseases. There are abundant pericytes which possess the characteristics of stem cells in the neurovascular unit. Due to the close relationship between pericytes and endothelial cells, the exosomes of pericytes can be taken up by endothelial cells more easily. There are fewer studies about the therapeutic potential of the exosomes derived from pericytes on SCI now. In this study, exosomes of pericytes were transplanted into the mice with SCI to study the restoration of motor function and explore the underlying mechanism. We found that the exosomes derived from pericytes could reduce pathological changes, improve the motor function, the blood flow and oxygen deficiency after SCI. In addition, the exosomes could improve the endothelial ability to regulate blood flow, protect the blood-spinal cord barrier, reduce edema, decrease the expression of HIF-1α, Bax, Aquaporin-4, and MMP2, increase the expression of Claudin-5, bcl-2 and inhibit apoptosis. The experiments in vitro proved that exosomes derived from pericytes could protect the barrier of spinal cord microvascular endothelial cells under hypoxia condition, which was related to PTEN/AKT pathway. In summary, our study showed that exosomes of pericytes had therapeutic prospects for SCI.https://www.frontiersin.org/article/10.3389/fnins.2019.00319/fullpericytesexosomesspinal cord injurymicrocirculationmicrovascular |
| spellingShingle | Xiaochen Yuan Qingbin Wu Peng Wang Yingli Jing Haijiang Yao Yinshan Tang Zhigang Li Honggang Zhang Ruijuan Xiu Exosomes Derived From Pericytes Improve Microcirculation and Protect Blood–Spinal Cord Barrier After Spinal Cord Injury in Mice Frontiers in Neuroscience pericytes exosomes spinal cord injury microcirculation microvascular |
| title | Exosomes Derived From Pericytes Improve Microcirculation and Protect Blood–Spinal Cord Barrier After Spinal Cord Injury in Mice |
| title_full | Exosomes Derived From Pericytes Improve Microcirculation and Protect Blood–Spinal Cord Barrier After Spinal Cord Injury in Mice |
| title_fullStr | Exosomes Derived From Pericytes Improve Microcirculation and Protect Blood–Spinal Cord Barrier After Spinal Cord Injury in Mice |
| title_full_unstemmed | Exosomes Derived From Pericytes Improve Microcirculation and Protect Blood–Spinal Cord Barrier After Spinal Cord Injury in Mice |
| title_short | Exosomes Derived From Pericytes Improve Microcirculation and Protect Blood–Spinal Cord Barrier After Spinal Cord Injury in Mice |
| title_sort | exosomes derived from pericytes improve microcirculation and protect blood spinal cord barrier after spinal cord injury in mice |
| topic | pericytes exosomes spinal cord injury microcirculation microvascular |
| url | https://www.frontiersin.org/article/10.3389/fnins.2019.00319/full |
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