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人脐带来源间充质干细胞细胞外囊泡的蛋白质组学特征及其治疗阿尔茨海默病的治疗潜力评估。

Proteomic characterization of hUC-MSC extracellular vesicles and evaluation of its therapeutic potential to treat Alzheimer's disease.

机构信息

Ministry of Education Key Laboratory of Molecular and Cellular Biology, Hebei Anti-Tumour Molecular Target Technology Innovation Center, College of Life Science, Hebei Normal University, Shijiazhuang, 050024, China.

Jianyuan Precision Medicines (Zhangjiakou) Co., Ltd., Zhangjiakou, 075000, China.

出版信息

Sci Rep. 2024 Mar 12;14(1):5959. doi: 10.1038/s41598-024-56549-6.

DOI:10.1038/s41598-024-56549-6
PMID:38472335
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10933327/
Abstract

In recent years, human umbilical cord mesenchymal stem cell (hUC-MSC) extracellular vesicles (EVs) have been used as a cell replacement therapy and have been shown to effectively overcome some of the disadvantages of cell therapy. However, the specific mechanism of action of EVs is still unclear, and there is no appropriate system for characterizing the differences in the molecular active substances of EVs produced by cells in different physiological states. We used a data-independent acquisition (DIA) quantitative proteomics method to identify and quantify the protein composition of two generations EVs from three different donors and analysed the function and possible mechanism of action of the proteins in EVs of hUC-MSCs via bioinformatics. By comparative proteomic analysis, we characterized the different passages EVs. Furthermore, we found that adaptor-related protein complex 2 subunit alpha 1 (AP2A1) and adaptor-related protein complex 2 subunit beta 1 (AP2B1) in hUC-MSC-derived EVs may play a significant role in the treatment of Alzheimer's disease (AD) by regulating the synaptic vesicle cycle signalling pathway. Our work provides a direction for batch-to-batch quality control of hUC-MSC-derived EVs and their application in AD treatment.

摘要

近年来，人脐带间充质干细胞（hUC-MSC）细胞外囊泡（EVs）已被用作细胞替代疗法，已被证明能有效克服细胞疗法的一些缺点。然而，EVs 的具体作用机制仍不清楚，也没有适当的系统来描述不同生理状态下细胞产生的 EVs 中分子活性物质的差异。我们使用了一种数据非依赖性采集（DIA）定量蛋白质组学方法来鉴定和定量三个不同供体来源的两代 EVs 的蛋白质组成，并通过生物信息学分析研究 hUC-MSCs EVs 中蛋白质的功能和可能的作用机制。通过比较蛋白质组学分析，我们对不同传代的 EVs 进行了特征描述。此外，我们发现 hUC-MSC 来源的 EVs 中的衔接蛋白相关复合物 2 亚基α1（AP2A1）和衔接蛋白相关复合物 2 亚基β1（AP2B1）可能通过调节突触小泡循环信号通路在阿尔茨海默病（AD）的治疗中发挥重要作用。我们的工作为 hUC-MSC 衍生 EVs 的批间质量控制及其在 AD 治疗中的应用提供了一个方向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4518/10933327/1a4f4e687ada/41598_2024_56549_Fig7_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4518/10933327/1a4f4e687ada/41598_2024_56549_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4518/10933327/6a0e5f300835/41598_2024_56549_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4518/10933327/7f14ac4cb8a8/41598_2024_56549_Fig2_HTML.jpg
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