Bone Mesenchymal Stem Cell-Derived Extracellular Vesicles Promote Recovery Following Spinal Cord Injury via Improvement of the Integrity of the Blood-Spinal Cord Barrier
Mesenchymal stem cell (MSC) transplantation has been shown to represent a potential treatment for traumatic spinal cord injury (SCI). However, there are several obstacles that need to be overcome before MSCs can be considered for clinical application, such as failure of MSCs to reach the spinal cord...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-03-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fnins.2019.00209/full |
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| author | Yanhui Lu Yanhui Lu Yan Zhou Ruiyi Zhang Ruiyi Zhang Lulu Wen Kaimin Wu Yanfei Li Yaobing Yao Ranran Duan Yanjie Jia |
| author_facet | Yanhui Lu Yanhui Lu Yan Zhou Ruiyi Zhang Ruiyi Zhang Lulu Wen Kaimin Wu Yanfei Li Yaobing Yao Ranran Duan Yanjie Jia |
| author_sort | Yanhui Lu |
| collection | DOAJ |
| description | Mesenchymal stem cell (MSC) transplantation has been shown to represent a potential treatment for traumatic spinal cord injury (SCI). However, there are several obstacles that need to be overcome before MSCs can be considered for clinical application, such as failure of MSCs to reach the spinal cord lesion core and possible tumor formation. Recent studies have suggested that MSC treatment is beneficial owing to paracrine-secreted factors. Extracellular vesicles are considered to be some of the most valuable paracrine molecules. However, the therapeutic mechanism of extracellular vesicles on spinal cord injury has not been studied clearly. Therefore, our study investigated the effect of systemic administration of extracellular vesicles on the loss of motor function after SCI and examined the potential mechanisms underlying their effects. Disruption of the blood-spinal cord barrier (BSCB) is a crucial factor that can be detrimental to motor function recovery. Pericytes are an important component of the neurovascular unit, and play a pivotal role in maintaining the structural integrity of the BSCB. Our study demonstrated that administration of bone mesenchymal stem cell-derived extracellular vesicles (BMSC-EV) reduced brain cell death, enhanced neuronal survival and regeneration, and improved motor function compared with the administration of BMSC-EV free culture media (EV-free CM). Besides, the BSCB was attenuated and pericyte coverage was significantly decreased in vivo. Furthermore, we found that exosomes reduced pericyte migration via downregulation of NF-κB p65 signaling, with a consequent decrease in the permeability of the BSCB. In summary, we identified that extracellular vesicles treatment suppressed the migration of pericytes and further improved the integrity of the BSCB via NF-κB p65 signaling in pericytes. Our data suggest that extracellular vesicles may serve as a promising treatment strategy for SCI. |
| first_indexed | 2024-12-13T09:40:20Z |
| format | Article |
| id | doaj.art-3cf38810c5e642748fdc085ed91f4494 |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-12-13T09:40:20Z |
| publishDate | 2019-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-3cf38810c5e642748fdc085ed91f44942022-12-21T23:52:13ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2019-03-011310.3389/fnins.2019.00209443376Bone Mesenchymal Stem Cell-Derived Extracellular Vesicles Promote Recovery Following Spinal Cord Injury via Improvement of the Integrity of the Blood-Spinal Cord BarrierYanhui Lu0Yanhui Lu1Yan Zhou2Ruiyi Zhang3Ruiyi Zhang4Lulu Wen5Kaimin Wu6Yanfei Li7Yaobing Yao8Ranran Duan9Yanjie Jia10Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaAcademy of Medical Sciences, Zhengzhou University, Zhengzhou, ChinaDepartment of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaAcademy of Medical Sciences, Zhengzhou University, Zhengzhou, ChinaDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaMesenchymal stem cell (MSC) transplantation has been shown to represent a potential treatment for traumatic spinal cord injury (SCI). However, there are several obstacles that need to be overcome before MSCs can be considered for clinical application, such as failure of MSCs to reach the spinal cord lesion core and possible tumor formation. Recent studies have suggested that MSC treatment is beneficial owing to paracrine-secreted factors. Extracellular vesicles are considered to be some of the most valuable paracrine molecules. However, the therapeutic mechanism of extracellular vesicles on spinal cord injury has not been studied clearly. Therefore, our study investigated the effect of systemic administration of extracellular vesicles on the loss of motor function after SCI and examined the potential mechanisms underlying their effects. Disruption of the blood-spinal cord barrier (BSCB) is a crucial factor that can be detrimental to motor function recovery. Pericytes are an important component of the neurovascular unit, and play a pivotal role in maintaining the structural integrity of the BSCB. Our study demonstrated that administration of bone mesenchymal stem cell-derived extracellular vesicles (BMSC-EV) reduced brain cell death, enhanced neuronal survival and regeneration, and improved motor function compared with the administration of BMSC-EV free culture media (EV-free CM). Besides, the BSCB was attenuated and pericyte coverage was significantly decreased in vivo. Furthermore, we found that exosomes reduced pericyte migration via downregulation of NF-κB p65 signaling, with a consequent decrease in the permeability of the BSCB. In summary, we identified that extracellular vesicles treatment suppressed the migration of pericytes and further improved the integrity of the BSCB via NF-κB p65 signaling in pericytes. Our data suggest that extracellular vesicles may serve as a promising treatment strategy for SCI.https://www.frontiersin.org/article/10.3389/fnins.2019.00209/fullextracellular vesiclesbone mesenchymal stromal cellsspinal cord injuryblood spinal cord barrierpericytesmigration |
| spellingShingle | Yanhui Lu Yanhui Lu Yan Zhou Ruiyi Zhang Ruiyi Zhang Lulu Wen Kaimin Wu Yanfei Li Yaobing Yao Ranran Duan Yanjie Jia Bone Mesenchymal Stem Cell-Derived Extracellular Vesicles Promote Recovery Following Spinal Cord Injury via Improvement of the Integrity of the Blood-Spinal Cord Barrier Frontiers in Neuroscience extracellular vesicles bone mesenchymal stromal cells spinal cord injury blood spinal cord barrier pericytes migration |
| title | Bone Mesenchymal Stem Cell-Derived Extracellular Vesicles Promote Recovery Following Spinal Cord Injury via Improvement of the Integrity of the Blood-Spinal Cord Barrier |
| title_full | Bone Mesenchymal Stem Cell-Derived Extracellular Vesicles Promote Recovery Following Spinal Cord Injury via Improvement of the Integrity of the Blood-Spinal Cord Barrier |
| title_fullStr | Bone Mesenchymal Stem Cell-Derived Extracellular Vesicles Promote Recovery Following Spinal Cord Injury via Improvement of the Integrity of the Blood-Spinal Cord Barrier |
| title_full_unstemmed | Bone Mesenchymal Stem Cell-Derived Extracellular Vesicles Promote Recovery Following Spinal Cord Injury via Improvement of the Integrity of the Blood-Spinal Cord Barrier |
| title_short | Bone Mesenchymal Stem Cell-Derived Extracellular Vesicles Promote Recovery Following Spinal Cord Injury via Improvement of the Integrity of the Blood-Spinal Cord Barrier |
| title_sort | bone mesenchymal stem cell derived extracellular vesicles promote recovery following spinal cord injury via improvement of the integrity of the blood spinal cord barrier |
| topic | extracellular vesicles bone mesenchymal stromal cells spinal cord injury blood spinal cord barrier pericytes migration |
| url | https://www.frontiersin.org/article/10.3389/fnins.2019.00209/full |
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