中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (10): 2246-2251.doi: 10.4103/1673-5374.369114

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

骨髓间充质干细胞来源外泌体是治疗缺血性脑卒中的一种潜在方法

  

  • 出版日期:2023-10-15 发布日期:2023-03-28
  • 基金资助:
    国家自然科学基金项目（81971231）；辽宁省自然科学基金项目（2022-MS-391）；辽宁省教育厅科研项目（JYTQN2020011，LJKQZ2021147）

Exosomes from bone marrow mesenchymal stem cells are a potential treatment for ischemic stroke

Chang Liu1, #, Tian-Hui Yang1, #, Hong-Dan Li2, Gong-Zhe Li3, Jia Liang2, *, Peng Wang1, *   

  1. 1Liaoning Provincial Key Laboratory of Neurodegenerative Diseases and Department of Neurobiology, Jinzhou Medical University, Jinzhou, Liaoning Province, China; 2Institute of Life Science, Jinzhou Medical University, Jinzhou, Liaoning Province, China; 3College of Pharmacy, Jinzhou Medical University, Jinzhou, Liaoning Province, China
  • Online:2023-10-15 Published:2023-03-28
  • Contact: Jia Liang, PhD, liangjia@jzmu.edu.cn; Peng Wang, PhD, wangpeng@jzmu.edu.cn.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, No. 81971231 (to JL); the Natural Science Foundation of Liaoning Province, No. 2022-MS-391 (to PW); and the Scientific Research Project from the Education Department of Liaoning Province, Nos. JYTQN2020011 (to PW), LJKQZ2021147 (to JL).

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摘要：

骨髓间充质干细胞来源的外泌体具有易于扩增和储存、肿瘤形成风险低以及免疫原性低等特点，同时具有抗炎作用，其对缺血性脑损伤的治疗作用已得到广泛关注，但其作用机制尚不十分明确。因此实验首先以线栓法诱导大脑中动脉闭塞建立缺血性脑损伤小鼠模型，并于30min后尾静脉注射人骨髓间充质干细胞来源外泌体，结果显示，骨髓间充质干细胞来源的外泌体移植能缩小缺血性脑卒中小鼠脑梗死体积，增加脑梗死半暗带中白细胞介素33和生长刺激表达基因2蛋白的水平，并改善神经功能。体外实验结果显示，氧糖剥夺星形胶质细胞条件培养基联合骨髓间充质干细胞来源的外泌体可提升原代皮质神经元的存活率，而IL-33 siRNA或ST2 siRNA转染的氧糖剥夺星形胶质细胞条件培养基联合骨髓间充质干细胞来源的外泌体干预的原代皮质神经元的存活率显著下降。表明骨髓间充质干细胞来源的外泌体是通过星形胶质细胞中白细胞介素33/生长刺激表达基因2蛋白信号通路抑制氧糖剥夺诱导的神经元死亡。提示骨髓间充质干细胞来源的外泌体可通过调节白细胞介素33/生长刺激表达基因2信号蛋白通路减轻缺血诱导的脑损伤，因而骨髓间充质干细胞来源的外泌体可能是治疗缺血性脑卒中的一种潜在方法。

https://orcid.org/0000-0001-7311-1260 (Jia Liang); https://orcid.org/0000-0001-9660-0147 (Peng Wang)

关键词: 外泌体, 骨髓间充质干细胞, 缺血性脑卒中, 星形胶质细胞, 白细胞介素33, 生长刺激表达基因2信号蛋白, 神经元, 脑损伤, 神经功能

Abstract: Exosomes derived from human bone marrow mesenchymal stem cells (MSC-Exo) are characterized by easy expansion and storage, low risk of tumor formation, low immunogenicity, and anti-inflammatory effects. The therapeutic effects of MSC-Exo on ischemic stroke have been widely explored. However, the underlying mechanism remains unclear. In this study, we established a mouse model of ischemic brain injury induced by occlusion of the middle cerebral artery using the thread bolt method and injected MSC-Exo into the tail vein. We found that administration of MSC-Exo reduced the volume of cerebral infarction in the ischemic brain injury mouse model, increased the levels of interleukin-33 (IL-33) and suppression of tumorigenicity 2 receptor (ST2) in the penumbra of cerebral infarction, and improved neurological function. In vitro results showed that astrocyte-conditioned medium of cells deprived of both oxygen and glucose, to simulate ischemia conditions, combined with MSC-Exo increased the survival rate of primary cortical neurons. However, after transfection by IL-33 siRNA or ST2 siRNA, the survival rate of primary cortical neurons was markedly decreased. These results indicated that MSC-Exo inhibited neuronal death induced by oxygen and glucose deprivation through the IL-33/ST2 signaling pathway in astrocytes. These findings suggest that MSC-Exo may reduce ischemia-induced brain injury through regulating the IL-33/ST2 signaling pathway. Therefore, MSC-Exo may be a potential therapeutic method for ischemic stroke.

Key words: astrocytes, bone marrow mesenchymal stem cells, brain injury, exosome, IL-33, inflammation, ischemic stroke, neurological function, neuron, ST2