Exosomes derived from bone marrow mesenchymal stem cells protect the injured spinal cord by inhibiting pericyte pyroptosis
Mesenchymal stem cell (MSC) transplantation is a promising treatment strategy for spinal cord injury, but immunological rejection and possible tumor formation limit its application. The therapeutic effects of MSCs mainly depend on their release of soluble paracrine factors. Exosomes are essential fo...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Medknow Publications
2022-01-01
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| Series: | Neural Regeneration Research |
| Subjects: | |
| Online Access: | http://www.nrronline.org/article.asp?issn=1673-5374;year=2022;volume=17;issue=1;spage=194;epage=202;aulast=Zhou |
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| author | Yan Zhou Lu-Lu Wen Yan-Fei Li Kai-Min Wu Ran-Ran Duan Yao-Bing Yao Li-Jun Jing Zhe Gong Jun-Fang Teng Yan-Jie Jia |
| author_facet | Yan Zhou Lu-Lu Wen Yan-Fei Li Kai-Min Wu Ran-Ran Duan Yao-Bing Yao Li-Jun Jing Zhe Gong Jun-Fang Teng Yan-Jie Jia |
| author_sort | Yan Zhou |
| collection | DOAJ |
| description | Mesenchymal stem cell (MSC) transplantation is a promising treatment strategy for spinal cord injury, but immunological rejection and possible tumor formation limit its application. The therapeutic effects of MSCs mainly depend on their release of soluble paracrine factors. Exosomes are essential for the secretion of these paracrine effectors. Bone marrow mesenchymal stem cell-derived exosomes (BMSC-EXOs) can be substituted for BMSCs in cell transplantation. However, the underlying mechanisms remain unclear. In this study, a rat model of T10 spinal cord injury was established using the impact method. Then, 30 minutes and 1 day after spinal cord injury, the rats were administered 200 μL exosomes via the tail vein (200 μg/mL; approximately 1 × 106 BMSCs). Treatment with BMSC-EXOs greatly reduced neuronal cell death, improved myelin arrangement and reduced myelin loss, increased pericyte/endothelial cell coverage on the vascular wall, decreased blood-spinal cord barrier leakage, reduced caspase 1 expression, inhibited interleukin-1β release, and accelerated locomotor functional recovery in rats with spinal cord injury. In the cell culture experiment, pericytes were treated with interferon-γ and tumor necrosis factor-α. Then, Lipofectamine 3000 was used to deliver lipopolysaccharide into the cells, and the cells were co-incubated with adenosine triphosphate to simulate injury in vitro. Pre-treatment with BMSC-EXOs for 8 hours greatly reduced pericyte pyroptosis and increased pericyte survival rate. These findings suggest that BMSC-EXOs may protect pericytes by inhibiting pyroptosis and by improving blood-spinal cord barrier integrity, thereby promoting the survival of neurons and the extension of nerve fibers, and ultimately improving motor function in rats with spinal cord injury. All protocols were conducted with the approval of the Animal Ethics Committee of Zhengzhou University on March 16, 2019. |
| first_indexed | 2024-12-23T04:15:54Z |
| format | Article |
| id | doaj.art-55c235a2c9a848e2a519f4c56d911c0b |
| institution | Directory Open Access Journal |
| issn | 1673-5374 |
| language | English |
| last_indexed | 2024-12-23T04:15:54Z |
| publishDate | 2022-01-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Neural Regeneration Research |
| spelling | doaj.art-55c235a2c9a848e2a519f4c56d911c0b2022-12-21T18:00:22ZengWolters Kluwer Medknow PublicationsNeural Regeneration Research1673-53742022-01-0117119420210.4103/1673-5374.314323Exosomes derived from bone marrow mesenchymal stem cells protect the injured spinal cord by inhibiting pericyte pyroptosisYan ZhouLu-Lu WenYan-Fei LiKai-Min WuRan-Ran DuanYao-Bing YaoLi-Jun JingZhe GongJun-Fang TengYan-Jie JiaMesenchymal stem cell (MSC) transplantation is a promising treatment strategy for spinal cord injury, but immunological rejection and possible tumor formation limit its application. The therapeutic effects of MSCs mainly depend on their release of soluble paracrine factors. Exosomes are essential for the secretion of these paracrine effectors. Bone marrow mesenchymal stem cell-derived exosomes (BMSC-EXOs) can be substituted for BMSCs in cell transplantation. However, the underlying mechanisms remain unclear. In this study, a rat model of T10 spinal cord injury was established using the impact method. Then, 30 minutes and 1 day after spinal cord injury, the rats were administered 200 μL exosomes via the tail vein (200 μg/mL; approximately 1 × 106 BMSCs). Treatment with BMSC-EXOs greatly reduced neuronal cell death, improved myelin arrangement and reduced myelin loss, increased pericyte/endothelial cell coverage on the vascular wall, decreased blood-spinal cord barrier leakage, reduced caspase 1 expression, inhibited interleukin-1β release, and accelerated locomotor functional recovery in rats with spinal cord injury. In the cell culture experiment, pericytes were treated with interferon-γ and tumor necrosis factor-α. Then, Lipofectamine 3000 was used to deliver lipopolysaccharide into the cells, and the cells were co-incubated with adenosine triphosphate to simulate injury in vitro. Pre-treatment with BMSC-EXOs for 8 hours greatly reduced pericyte pyroptosis and increased pericyte survival rate. These findings suggest that BMSC-EXOs may protect pericytes by inhibiting pyroptosis and by improving blood-spinal cord barrier integrity, thereby promoting the survival of neurons and the extension of nerve fibers, and ultimately improving motor function in rats with spinal cord injury. All protocols were conducted with the approval of the Animal Ethics Committee of Zhengzhou University on March 16, 2019.http://www.nrronline.org/article.asp?issn=1673-5374;year=2022;volume=17;issue=1;spage=194;epage=202;aulast=Zhoublood-spinal cord barrier; edema; exosome; pericyte; nod1; pro-caspase 1; pyroptosis; spinal cord injury |
| spellingShingle | Yan Zhou Lu-Lu Wen Yan-Fei Li Kai-Min Wu Ran-Ran Duan Yao-Bing Yao Li-Jun Jing Zhe Gong Jun-Fang Teng Yan-Jie Jia Exosomes derived from bone marrow mesenchymal stem cells protect the injured spinal cord by inhibiting pericyte pyroptosis Neural Regeneration Research blood-spinal cord barrier; edema; exosome; pericyte; nod1; pro-caspase 1; pyroptosis; spinal cord injury |
| title | Exosomes derived from bone marrow mesenchymal stem cells protect the injured spinal cord by inhibiting pericyte pyroptosis |
| title_full | Exosomes derived from bone marrow mesenchymal stem cells protect the injured spinal cord by inhibiting pericyte pyroptosis |
| title_fullStr | Exosomes derived from bone marrow mesenchymal stem cells protect the injured spinal cord by inhibiting pericyte pyroptosis |
| title_full_unstemmed | Exosomes derived from bone marrow mesenchymal stem cells protect the injured spinal cord by inhibiting pericyte pyroptosis |
| title_short | Exosomes derived from bone marrow mesenchymal stem cells protect the injured spinal cord by inhibiting pericyte pyroptosis |
| title_sort | exosomes derived from bone marrow mesenchymal stem cells protect the injured spinal cord by inhibiting pericyte pyroptosis |
| topic | blood-spinal cord barrier; edema; exosome; pericyte; nod1; pro-caspase 1; pyroptosis; spinal cord injury |
| url | http://www.nrronline.org/article.asp?issn=1673-5374;year=2022;volume=17;issue=1;spage=194;epage=202;aulast=Zhou |
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