Chen Puwen, Wang Fangsheng, Ling Baodian, Zhu Yifan, Lin Haihong, Huang Junyun, Wang Xiaoling
The First School of Clinical Medicine, Gannan Medical University, Ganzhou, 341000, People's Republic of China.
Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, People's Republic of China.
Int J Nanomedicine. 2025 Jul 2;20:8547-8565. doi: 10.2147/IJN.S526945. eCollection 2025.
Neurodegenerative diseases are a group of chronic diseases characterized by a gradual loss of neurons that worsens over time and dysfunction. These diseases are extremely harmful, not only affecting the physical health of the patients, but also having a serious impact on their quality of life. They mainly include Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Amyotrophic lateral sclerosis (ALS), etc. Their pathogenesis is complex, and it is difficult for the existing treatments to effectively slow down the progression of the disease. In recent years, Mesenchymal Stem Cells (MSCs) have received widespread attention for their anti-inflammatory, immunomodulatory and neuroprotective properties. In this context, MSC-derived Extracellular Vesicles (MSC-EVs) have demonstrated unique therapeutic potential as a cell-free therapeutic strategy. MSC-EVs are rich in bioactive substances such as proteins, lipids, mRNAs and miRNAs, which can pass through the blood-brain barrier and be targeted to the diseased area to regulate neuronal survival, synaptic plasticity and neuroinflammatory responses. In addition, compared with stem cell therapy, MSC-EVs have the advantages of low immunogenicity, easy storage and transportation, and avoiding ethical controversies. However, their clinical application still faces challenges: standardized isolation and purification techniques have not been unified, vesicle loading efficiency and targeting need to be further optimized, and long-term safety needs to be systematically evaluated. This review focuses on the role of MSC-EVs in the development of neurological diseases and explores their possible dual roles, both favorable and unfavorable, in the context of neurological diseases. In addition, this review provides a review of current studies on EVs as potential biomarkers for the diagnosis and treatment of neurodegenerative diseases and provides a comprehensive review of the prospects and challenges of MSC-EVs in clinical applications.
神经退行性疾病是一组慢性疾病,其特征是神经元逐渐丧失,且随着时间的推移病情会恶化并出现功能障碍。这些疾病极具危害性,不仅影响患者的身体健康,还对其生活质量产生严重影响。它们主要包括阿尔茨海默病(AD)、帕金森病(PD)、亨廷顿病(HD)、肌萎缩侧索硬化症(ALS)等。其发病机制复杂,现有治疗方法难以有效减缓疾病进展。近年来,间充质干细胞(MSCs)因其抗炎、免疫调节和神经保护特性而受到广泛关注。在此背景下,源自间充质干细胞的细胞外囊泡(MSC-EVs)作为一种无细胞治疗策略已展现出独特的治疗潜力。MSC-EVs富含蛋白质、脂质、mRNA和miRNA等生物活性物质,它们可以穿过血脑屏障并靶向病变区域,从而调节神经元存活、突触可塑性和神经炎症反应。此外,与干细胞治疗相比,MSC-EVs具有免疫原性低、易于储存和运输以及避免伦理争议等优点。然而,其临床应用仍面临挑战:标准化的分离和纯化技术尚未统一,囊泡装载效率和靶向性有待进一步优化,长期安全性需要进行系统评估。本综述重点关注MSC-EVs在神经疾病发展中的作用,并探讨它们在神经疾病背景下可能存在的有利和不利双重作用。此外,本综述还对当前关于EVs作为神经退行性疾病诊断和治疗潜在生物标志物的研究进行了综述,并全面回顾了MSC-EVs在临床应用中的前景和挑战。
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