Stem cell derived extracellular vesicles therapy for perinatal brain injury: A systematic review & meta-analysis of preclinical studies and a potential path to clinic

IF 3.7 3区医学 Q2 NEUROSCIENCES

Brain Research Bulletin Pub Date : 2025-07-27 DOI:10.1016/j.brainresbull.2025.111481

Xiaolin Guo , Tingting Peng , Mengru Zhong , Simian Cai , Lu He , Kaishou Xu

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引用次数: 0

Abstract

Background

Perinatal brain injury (PBI) is a significant cause of neonatal death and childhood disability. Current treatments for PBI are limited and ineffective. Stem cell derived extracellular vesicles (SC-EVs) have shown promising therapeutic potential in addressing PBI. We aimed to assess the effectiveness and potential mechanisms of SC-EVs therapy on behavioral and pathological outcomes in animal models of PBI.

Methods

We searched six databases (MEDLINE, Embase, Scopus, PubMed, ProQuest, and Web of Science) for articles on the therapeutic effects of SC-EVs in animal models of PBI. We extracted neurobehavioral and pathological results related to brain injury and used a random-effects model to calculate the standardized mean difference and confidence interval.

Results

Twenty-five articles met the inclusion criteria. Treatment with SC-EVs improved cerebral infarct size and tissue edema, as well as the recovery of cognition and motor function. The mechanism of action may be related to the inhibition of apoptosis, microglia activation, astrogliosis, and pro-inflammatory factor release, further promoting neuronal protection, remyelination, and angiogenesis. Study quality assessment found no studies to be at high risk, and there was significant heterogeneity among studies. Sensitivity analysis and subgroup analysis did not identify the source of heterogeneity.

Conclusion

SC-EVs might improve cognitive and motor functions, as well as brain microstructure, by exerting anti-apoptotic and anti-neuroinflammatory effects. This provides a theoretical basis for using cell-free therapies to prevent and treat PBI and supports the translation of SC-EVs from preclinical models to human applications.

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干细胞来源的细胞外囊泡治疗围产期脑损伤：临床前研究的系统回顾和荟萃分析以及临床的潜在途径。

背景：围产期脑损伤（PBI）是新生儿死亡和儿童残疾的重要原因。目前对PBI的治疗是有限和无效的。干细胞衍生的细胞外囊泡（sc - ev）在治疗PBI方面显示出良好的治疗潜力。我们的目的是评估sc - ev治疗对PBI动物模型的行为和病理结果的有效性和潜在机制。方法：检索MEDLINE、Embase、Scopus、PubMed、ProQuest、Web of Science等6个数据库，检索有关sc - ev对PBI动物模型治疗效果的文章。我们提取了与脑损伤相关的神经行为和病理结果，并使用随机效应模型计算标准化平均差和置信区间。结果：25篇文章符合纳入标准。sc - ev治疗可改善脑梗死面积和组织水肿，以及认知和运动功能的恢复。其作用机制可能与抑制细胞凋亡、小胶质细胞活化、星形胶质细胞形成和促炎因子释放有关，进而促进神经元保护、髓鞘再生和血管生成。研究质量评估未发现有高风险的研究，研究之间存在显著的异质性。敏感性分析和亚组分析未发现异质性的来源。结论：sc - ev可能通过发挥抗细胞凋亡和抗神经炎症作用，改善认知和运动功能，改善脑结构。这为使用无细胞疗法预防和治疗PBI提供了理论基础，并支持sc - ev从临床前模型向人类应用的转化。

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

Brain Research Bulletin 医学-神经科学

CiteScore

6.90

自引率

2.60%

发文量

253

审稿时长

67 days

期刊介绍： The Brain Research Bulletin (BRB) aims to publish novel work that advances our knowledge of molecular and cellular mechanisms that underlie neural network properties associated with behavior, cognition and other brain functions during neurodevelopment and in the adult. Although clinical research is out of the Journal''s scope, the BRB also aims to publish translation research that provides insight into biological mechanisms and processes associated with neurodegeneration mechanisms, neurological diseases and neuropsychiatric disorders. The Journal is especially interested in research using novel methodologies, such as optogenetics, multielectrode array recordings and life imaging in wild-type and genetically-modified animal models, with the goal to advance our understanding of how neurons, glia and networks function in vivo.