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CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
骨髓间充质干细胞外泌体来源 microRNA-216a-5p 对脊髓损伤中运动功能、神经损伤和小胶质细胞炎症的影响
英文原题：Bone marrow mesenchymal stem cell exosomes-derived microRNA-216a-5p on locomotor performance, neuronal injury, and microglia inflammation in spinal cord injury.
查看英文原题
Bone marrow mesenchymal stem cell exosomes-derived microRNA-216a-5p on locomotor performance, neuronal injury, and microglia inflammation in spinal cord injury.
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中文摘要
背景
MicroRNA-216a-5p（miR-216a-5p）可介导炎症反应和神经元损伤，参与脊髓损伤（SCI）的病理过程。本研究旨在探讨骨髓间充质干细胞外泌体（BMSC-Exo）来源的miR-216a-5p对SCI大鼠运动功能、神经元损伤及小胶质细胞介导炎症的影响。
方法
向SCI大鼠注射大鼠BMSC或BMSC-Exo，并采用GW4869抑制BMSC外泌体分泌。随后，向SCI大鼠注射miR-216a-5p过表达的BMSC-Exo（BMSC-miR-Exo）或阴性对照过表达BMSC-Exo（BMSC-NC-Exo）。
结果
注射BMSC或BMSC-Exo可改善运动功能（Basso、Beattie和Bresnahan评分，p<0.001）和神经元存活（NeuN+细胞，p<0.01），并减少神经元凋亡（TUNEL阳性率、裂解型caspase-3表达及B细胞淋巴瘤2表达，p<0.05）。此外，BMSC或BMSC-Exo可抑制小胶质细胞M1极化相关炎症，表现为IBA1+iNOS+细胞、肿瘤坏死因子、IL-1和IL-6减少（p<0.01）。值得注意的是，GW4869处理可削弱BMSC对上述指标的改善作用（多数p<0.05）。与BMSC-NC-Exo相比，注射BMSC-miR-Exo进一步改善运动功能（p<0.05），同时抑制神经元凋亡和小胶质细胞M1极化介导的炎症（均p<0.05）。此外，BMSC-miR-Exo可降低Toll样受体4（TLR4，p<0.01）、髓样分化因子88（p<0.05）及核因子κB（NF-κB，p<0.05）的表达。
结论
BMSC-Exo来源的miR-216a-5p可通过减轻神经元损伤和小胶质细胞介导的炎症促进SCI功能恢复，可能与抑制TLR4/NF-κB通路有关。
展开英文摘要原文
Background: MicroRNA-216a-5p (miR-216a-5p) mediates inflammatory responses and neuronal injury to participate in the pathology of spinal cord injury (SCI).
This study intended to explore the engagement of bone marrow mesenchymal stem cell exosomes (BMSC-Exo)-derived miR-216a-5p in locomotor performance, neuronal injury, and microglia-mediated inflammation in SCI rats. Methods: Rat BMSC or BMSC-Exo was injected into SCI rats. GW4869 treatment was adopted to suppress the exosome secretion from BMSC. Subsequently, miR-216a-5p-overexpressed BMSC-Exo (BMSC-miR-Exo) or negative-control-overexpressed BMSC-Exo (BMSC-NC-Exo) were injected into SCI rats.
Results: The injection of BMSC or BMSC-Exo enhanced locomotor performance reflected by Basso, Beattie & Bresnahan score ( p < 0. 001), and neuronal viability reflected by NeuN + cells ( p < 0. 01), but attenuated neuronal apoptosis reflected by TUNEL positive rate, cleaved-caspase-3 expression, and B-cell leukemia/lymphoma-2 expression ( p < 0. 05).
Additionally, the injection of BMSC or BMSC-Exo suppressed microglia M1 polarization-mediated inflammation reflected by IBA1 + iNOS + cells, tumor necrosis factor- , interleukin (IL)-1 , and IL-6 ( p < 0. 01).
Notably, the effect of BMSC on the above functions was retarded by the GW4869 treatment (most p < 0. 05). Subsequently, the injection of BMSC-miR-Exo further improved locomotor performance ( p < 0. 05), while inhibiting neuronal apoptosis ( p < 0. 05) and microglia M1 polarization-mediated inflammation ( p < 0. 05) compared to BMSC-NC-Exo. Interestingly, the injection of BMSC-miR-Exo reduced toll-like receptor 4 (TLR4) ( p < 0.
01), myeloid differentiation factor 88 ( p < 0. 05), and nuclear factor kappa B (NF- B) ( p < 0. 05) expressions versus BMSC-NC-Exo. Conclusion: BMSC-Exo-derived miR-216a-5p enhances functional recovery by attenuating neuronal injury and microglia-mediated inflammation in SCI, which may be attributable to its inhibition of the TLR4/NF- B pathway.
论文信息
- 作者
- Xue H、Ran B、Li J、Wang G、Chen B、Mao H
- 期刊
- Frontiers in cell and developmental biology2023
- 原文标识
- PubMed 37766965 · DOI 10.3389/fcell.2023.1227440
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