Microglial Responses to MSC-EVs Treatment in Animal and Cellular Models of Ischemic Stroke: a Systematic Review with Meta-analysis.

IF 4.3 2区 医学 Q1 NEUROSCIENCES
Molecular Neurobiology Pub Date : 2025-11-01 Epub Date: 2025-05-22 DOI:10.1007/s12035-025-05025-x
Luis Pedro Bernardi, Thomas Hugentobler Schlickmann, Giovanna Carello-Collar, Marco Antonio De Bastiani, Eduardo Rigon Zimmer, Elizandra Braganhol, Francieli Rohden, Diogo Onofre Souza
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引用次数: 0

Abstract

The modulation of microglial reactivity has emerged as a potential target for developing ischemic stroke therapies. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) possess immunomodulatory properties that may influence microglial responses following ischemia. However, individual studies assessing this influence have provided limited results. Therefore, we conducted a systematic review and meta-analysis to investigate whether MSC-EVs treatment alters microglial responses in animal and cellular models of ischemic stroke. In accordance with the PRISMA 2020 statement, we searched PubMed, Web of Science, and EMBASE until January 2025 for studies assessing cellular and molecular parameters of microglial reactivity following MSC-EVs treatment in models of ischemic stroke. We estimated treatment effects using a random-effects meta-analysis of standardized mean differences and estimated heterogeneity via the I2 statistic. The risk of bias was assessed using the SYRCLE questionnaire. The search identified 386 studies, 35 of which met the inclusion criteria. In animal models, MSC-EVs reduced the number, surface area, and fluorescence intensity of Iba1+ cells, as well as the number of Iba1+ cells co-expressing the pro-inflammatory markers CD16, CD32, CD85, and iNOS. Conversely, MSC-EVs increased the number of Iba1+ cells co-expressing the anti-inflammatory markers Arg-1 and CD206. In cellular models, we observed decreased concentrations of TNF-α, IL-1β, and IL-6 in the culture medium. Our meta-analysis consolidates the immunomodulatory effects of MSC-EVs on microglial responses to ischemia, underscoring the potential of microglia-specific therapeutics in the development of MSC-EVs-based and regenerative treatments for ischemic stroke.

缺血性脑卒中动物和细胞模型中小胶质细胞对msc - ev治疗的反应:一项系统综述和荟萃分析。
小胶质细胞反应性的调节已成为开发缺血性卒中治疗的潜在靶点。间充质干细胞衍生的细胞外囊泡(msc - ev)具有免疫调节特性,可能影响缺血后的小胶质细胞反应。然而,评估这种影响的个别研究提供了有限的结果。因此,我们进行了一项系统综述和荟萃分析,以研究msc - ev治疗是否会改变缺血性卒中动物和细胞模型中的小胶质细胞反应。根据PRISMA 2020声明,我们检索了PubMed、Web of Science和EMBASE,直到2023年10月,以评估缺血性卒中模型中msc - ev治疗后小胶质细胞反应性的细胞和分子参数。我们使用标准化平均差异的随机效应荟萃分析估计治疗效果,并通过I2统计量估计异质性。使用sycle问卷评估偏倚风险。检索确定了297项研究,其中27项符合纳入标准。在动物模型中,msc - ev减少了Iba1+细胞的数量、表面积和荧光强度,以及共表达促炎标志物CD16、CD32、CD85和iNOS的Iba1+细胞的数量。相反,msc - ev增加了共表达抗炎标志物Arg-1和CD206的Iba1+细胞的数量。在细胞模型中,我们观察到培养基中TNF-α、IL-1β和IL-6的浓度降低。我们的荟萃分析巩固了msc - ev对小胶质细胞缺血反应的免疫调节作用,强调了小胶质细胞特异性治疗在开发基于msc - ev的缺血性卒中再生治疗中的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Molecular Neurobiology
Molecular Neurobiology 医学-神经科学
CiteScore
9.00
自引率
2.00%
发文量
480
审稿时长
1 months
期刊介绍: Molecular Neurobiology is an exciting journal for neuroscientists needing to stay in close touch with progress at the forefront of molecular brain research today. It is an especially important periodical for graduate students and "postdocs," specifically designed to synthesize and critically assess research trends for all neuroscientists hoping to stay active at the cutting edge of this dramatically developing area. This journal has proven to be crucial in departmental libraries, serving as essential reading for every committed neuroscientist who is striving to keep abreast of all rapid developments in a forefront field. Most recent significant advances in experimental and clinical neuroscience have been occurring at the molecular level. Until now, there has been no journal devoted to looking closely at this fragmented literature in a critical, coherent fashion. Each submission is thoroughly analyzed by scientists and clinicians internationally renowned for their special competence in the areas treated.
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