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缺血性脑损伤中的间充质干细胞与外泌体:综述

Mesenchymal stem cells and exosomes in ischemic brain injury: a review.

作者信息

Xu Haiyan, Yang Lanlan, Wang Weitie, Zhang Chengwei

机构信息

Department of Rehabilitation Therapeutics, School of Nursing, Jilin University, Changchun, Jilin, China.

Department of Biliary and Pancreatic Internal Medicine, The Second Hospital of Jilin University, Changchun, Jilin, China.

出版信息

Front Genet. 2025 Aug 29;16:1639756. doi: 10.3389/fgene.2025.1639756. eCollection 2025.

DOI:10.3389/fgene.2025.1639756
PMID:40949877
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12425733/
Abstract

Stroke poses a serious threat to human health and life, serving as a leading cause of death and disability in adults. The incidence rate of stroke continues to rise annually. Following the onset of ischemic stroke, most patients experience a period of spontaneous recovery. Neural repair after cerebral ischemia is closely associated with neurovascular plasticity, which facilitates the regeneration and repair of nerves and blood vessels in the ischemic injury area. Mesenchymal stem cells (MSCs), adult stem cells isolated from bone marrow or other tissues, can differentiate into various cell types and possess characteristics such as self-renewal, low immunogenicity, and easy of isolation. Exosomes are regarded as the primary mediators of MSC functions. These specialized extracellular vesicles play critical roles in intercellular communication, targeted transport, and regulation of recipient cell functions through their surface molecules and cargo (e.g., proteins, RNA, and other bioactive factors). Studies demonstrate that MSCs and their exosomes participate in both neuronal and vascular endothelial cell damage and repair after stroke. They exert distinct effects at different stages of cerebral ischemia injury, promoting angiogenesis, neurogenesis, and reducing inflammation. While preclinical studies show promising therapeutic potential, clinical translation faces challenges such as standardization of exosome isolation, optimal dosing, delivery methods, and long-term safety evaluation. Future research should focus on overcoming these barriers to facilitate their application in stroke therapy. This review summarizes current research on the therapeutic potential of MSCs and their exosomes in ischemic brain injury.

摘要

中风对人类健康和生命构成严重威胁,是成年人死亡和残疾的主要原因。中风的发病率每年持续上升。缺血性中风发作后,大多数患者会经历一段自发恢复的时期。脑缺血后的神经修复与神经血管可塑性密切相关,神经血管可塑性有助于缺血损伤区域神经和血管的再生与修复。间充质干细胞(MSCs)是从骨髓或其他组织中分离出来的成体干细胞,能够分化为多种细胞类型,并具有自我更新、低免疫原性和易于分离等特性。外泌体被认为是MSCs功能的主要介导者。这些特殊的细胞外囊泡通过其表面分子和货物(如蛋白质、RNA和其他生物活性因子)在细胞间通讯、靶向运输和受体细胞功能调节中发挥关键作用。研究表明,MSCs及其外泌体参与中风后神经元和血管内皮细胞的损伤与修复。它们在脑缺血损伤的不同阶段发挥不同作用,促进血管生成、神经发生并减轻炎症。虽然临床前研究显示出有前景的治疗潜力,但临床转化面临着外泌体分离标准化、最佳剂量、给药方法和长期安全性评估等挑战。未来的研究应专注于克服这些障碍,以促进它们在中风治疗中的应用。本综述总结了目前关于MSCs及其外泌体在缺血性脑损伤治疗潜力的研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bba/12425733/0e9d08a12dd4/fgene-16-1639756-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bba/12425733/0e121e1b26e9/fgene-16-1639756-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bba/12425733/0e9d08a12dd4/fgene-16-1639756-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bba/12425733/0e121e1b26e9/fgene-16-1639756-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bba/12425733/0e9d08a12dd4/fgene-16-1639756-g002.jpg

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本文引用的文献

1
Regulation of blood-brain barrier integrity by brain microvascular endothelial cells in ischemic stroke: A therapeutic opportunity.脑微血管内皮细胞对缺血性脑卒中血脑屏障完整性的调节:一个治疗契机。
Eur J Pharmacol. 2025 Jun 5;996:177553. doi: 10.1016/j.ejphar.2025.177553. Epub 2025 Mar 25.
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The foam cell-derived exosomal miRNA Novel-3 drives neuroinflammation and ferroptosis during ischemic stroke.泡沫细胞衍生的外泌体微小RNA Novel-3在缺血性中风期间引发神经炎症和铁死亡。
Nat Aging. 2024 Dec;4(12):1845-1861. doi: 10.1038/s43587-024-00727-8. Epub 2024 Oct 28.
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Advances in therapies using mesenchymal stem cells and their exosomes for treatment of peripheral nerve injury: state of the art and future perspectives.
间充质干细胞及其外泌体治疗周围神经损伤的疗法进展:现状与未来展望
Neural Regen Res. 2025 Nov 1;20(11):3151-3171. doi: 10.4103/NRR.NRR-D-24-00235. Epub 2024 Oct 22.
4
3D-printing hydrogel programmed released exosomes to restore aortic medial degeneration through inhibiting VSMC ferroptosis in aortic dissection.3D 打印水凝胶程序性释放外泌体通过抑制主动脉夹层中 VSMC 铁死亡来恢复主动脉中层退变。
J Nanobiotechnology. 2024 Oct 4;22(1):600. doi: 10.1186/s12951-024-02821-w.
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Exosome-based drug delivery systems for enhanced neurological therapeutics.用于增强神经治疗的基于外泌体的药物递送系统。
Drug Deliv Transl Res. 2025 Apr;15(4):1121-1138. doi: 10.1007/s13346-024-01710-x. Epub 2024 Sep 26.
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Systemic administration of blood-derived exosomes induced by remote ischemic post-conditioning, by delivering a specific cluster of miRNAs, ameliorates ischemic damage and neurological function.远程缺血后处理诱导的血液源性外泌体经全身给药,通过递送特定的一组微小RNA,可改善缺血损伤和神经功能。
J Cereb Blood Flow Metab. 2024 Dec;44(12):1459-1471. doi: 10.1177/0271678X241270284. Epub 2024 Aug 11.
7
Metabolically Glycoengineered Neural Stem Cells Boost Neural Repair After Cardiac Arrest.代谢糖工程化神经干细胞促进心脏骤停后的神经修复。
Adv Funct Mater. 2024 Apr 25;34(17). doi: 10.1002/adfm.202309866. Epub 2023 Dec 22.
8
Anti-ferroptosis exosomes engineered for targeting M2 microglia to improve neurological function in ischemic stroke.靶向 M2 小胶质细胞的抗铁死亡外泌体工程改善缺血性脑卒中的神经功能。
J Nanobiotechnology. 2024 May 27;22(1):291. doi: 10.1186/s12951-024-02560-y.
9
Pericyte-derived exosomal miR-210 improves mitochondrial function and inhibits lipid peroxidation in vascular endothelial cells after traumatic spinal cord injury by activating JAK1/STAT3 signaling pathway.血管周细胞衍生的外泌体 miR-210 通过激活 JAK1/STAT3 信号通路改善创伤性脊髓损伤后血管内皮细胞的线粒体功能并抑制脂质过氧化。
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Exosomal circBBS2 inhibits ferroptosis by targeting miR-494 to activate SLC7A11 signaling in ischemic stroke.外泌体 circBBS2 通过靶向 miR-494 激活 SLC7A11 信号通路抑制缺血性脑卒中细胞铁死亡。
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