Zhdanova Daria Y, Bobkova Natalia V, Chaplygina Alina V, Svirshchevskaya Elena V, Poltavtseva Rimma A, Vodennikova Anastasia A, Chernyshev Vasiliy S, Sukhikh Gennadiy T
Institute of Cell Biophysics, Federal Research Center Pushchino Research Center for Biological Studies, Russian Academy of Sciences, Institutskaya 3, Pushchino, 142290 Moscow, Russia.
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Ulitsa M0iklukho-Maklaya 16/10, 117997 Moscow, Russia.
Int J Mol Sci. 2025 Apr 24;26(9):4026. doi: 10.3390/ijms26094026.
Alzheimer's disease (AD) is one of the most common progressive neurodegenerative diseases leading to impairments in memory, orientation, and behavior. However, significant work is still needed to fully understand the progression of such disease and develop novel therapeutic agents for AD prevention and treatment. Small extracellular vesicles (sEVs) have received attention in recent years due to their potential therapeutic effects on AD. The aim of this study was to determine the potential effect of sEVs in an in vitro model of AD. sEVs were isolated from human Wharton's jelly mesenchymal stem cells (MSCs) by asymmetric depth filtration, a method developed recently by us. AD was modeled in vitro using cells obtained from the hippocampi of newborn 5xFAD transgenic mice carrying mutations involved in familial AD. After isolation, sEVs underwent detailed characterization that included scanning electron microscopy, nanoparticle tracking analysis, confocal microscopy, Western blotting, and Luminex assay. When added to 5xFAD hippocampal cells, sEVs were nontoxic, colocalized with neurons and astrocytes, decreased the level of Aβ peptide, and increased the synaptic density. These results support the possibility that sEVs can improve brain cell function during aging, decrease the risk of AD, and potentially be used for AD therapeutics.
阿尔茨海默病（AD）是最常见的进行性神经退行性疾病之一，会导致记忆、定向和行为障碍。然而，要全面了解此类疾病的进展并开发用于预防和治疗AD的新型治疗药物，仍需要大量工作。近年来，小细胞外囊泡（sEVs）因其对AD的潜在治疗作用而受到关注。本研究的目的是确定sEVs在AD体外模型中的潜在作用。通过不对称深度过滤从人脐带间充质干细胞（MSCs）中分离sEVs，这是我们最近开发的一种方法。使用从携带家族性AD相关突变的新生5xFAD转基因小鼠海马中获得的细胞在体外建立AD模型。分离后，对sEVs进行了详细表征，包括扫描电子显微镜、纳米颗粒跟踪分析、共聚焦显微镜、蛋白质免疫印迹和Luminex检测。当添加到5xFAD海马细胞中时，sEVs无毒，与神经元和星形胶质细胞共定位，降低了Aβ肽水平，并增加了突触密度。这些结果支持了sEVs可以改善衰老过程中脑细胞功能、降低AD风险并有可能用于AD治疗的可能性。
