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从实验室到临床:一种通过模拟疾病微环境预处理间充质干细胞衍生外泌体的精准治疗策略

From laboratory to clinic: a precise treatment strategy of mesenchymal stem cells-derived exosomes pretreated by simulating disease microenvironment.

作者信息

Ye Hailian, He Qi, Qi Fang, Xu Guangchao, Qahar Mulan, Deng Chenliang, Wei Zairong

机构信息

Department of Burns and Plastic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China.

The 2011 Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China.

出版信息

Front Immunol. 2025 Jul 17;16:1609288. doi: 10.3389/fimmu.2025.1609288. eCollection 2025.

DOI:10.3389/fimmu.2025.1609288
PMID:40746527
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12310476/
Abstract

Mesenchymal Stem Cells (MSCs) and their secreted extracellular vesicles (EVs), particularly exosomes (Exos), have garnered significant attention for their potential in tissue repair, fibrosis, and tumor therapy. However, the therapeutic efficacy of mesenchymal stem cell-derived exosomes (MSC-Exos) is notably influenced by the disease-specific microenvironment. This review examines the mechanisms of action of MSCs and MSC-Exos in various diseases and analyzes the impact of inflammatory preconditioning on the functions and paracrine signaling of MSCs. We propose a personalized MSC preconditioning strategy based on the characteristics of the disease microenvironment to enhance the precision and efficacy of MSC-Exos therapy. Additionally, we discuss the limitations of traditional preconditioning strategies and introduce novel approaches for MSC preconditioning by simulating the disease microenvironment, such as using tissue homogenates and EVs derived from diseased tissues. These methods more accurately reflect the spatiotemporal features of the disease microenvironment, thereby improving the therapeutic potential of MSC-Exos. Finally, we explore the application of engineered exosomes loaded with key miRNAs targeting disease treatment, offering new insights for precision medicine.

摘要

间充质干细胞(MSCs)及其分泌的细胞外囊泡(EVs),特别是外泌体(Exos),因其在组织修复、纤维化和肿瘤治疗方面的潜力而备受关注。然而,间充质干细胞来源的外泌体(MSC-Exos)的治疗效果受到疾病特异性微环境的显著影响。本综述探讨了MSCs和MSC-Exos在各种疾病中的作用机制,并分析了炎症预处理对MSCs功能和旁分泌信号的影响。我们基于疾病微环境的特征提出了一种个性化的MSC预处理策略,以提高MSC-Exos治疗的精准性和疗效。此外,我们讨论了传统预处理策略的局限性,并介绍了通过模拟疾病微环境对MSC进行预处理的新方法,如使用组织匀浆和疾病组织来源的EVs。这些方法更准确地反映了疾病微环境的时空特征,从而提高了MSC-Exos的治疗潜力。最后,我们探索了装载靶向疾病治疗的关键miRNAs的工程化外泌体的应用,为精准医学提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8526/12310476/a835179a51f7/fimmu-16-1609288-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8526/12310476/9c046a351e18/fimmu-16-1609288-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8526/12310476/a835179a51f7/fimmu-16-1609288-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8526/12310476/9c046a351e18/fimmu-16-1609288-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8526/12310476/a835179a51f7/fimmu-16-1609288-g002.jpg

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本文引用的文献

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Anal Chim Acta. 2025 Mar 22;1344:343728. doi: 10.1016/j.aca.2025.343728. Epub 2025 Jan 25.
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Disease-derived circulating extracellular vesicle preconditioning: A promising strategy for precision mesenchymal stem cell therapy.疾病衍生的循环细胞外囊泡预处理:精准间充质干细胞治疗的一种有前景的策略。
Acta Pharm Sin B. 2024 Oct;14(10):4526-4543. doi: 10.1016/j.apsb.2024.06.027. Epub 2024 Jun 28.
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Targeting delivery of miR-146a via IMTP modified milk exosomes exerted cardioprotective effects by inhibiting NF-κB signaling pathway after myocardial ischemia-reperfusion injury.
通过 IMTP 修饰的牛奶外泌体靶向递送 miR-146a,通过抑制心肌缺血再灌注损伤后的 NF-κB 信号通路发挥心脏保护作用。
J Nanobiotechnology. 2024 Jul 1;22(1):382. doi: 10.1186/s12951-024-02631-0.
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Cationic-motif-modified exosomes for mRNA delivery to retinal photoreceptors.阳离子基序修饰的外泌体用于向视网膜光感受器递送 mRNA。
J Mater Chem B. 2024 Jul 31;12(30):7384-7400. doi: 10.1039/d4tb00849a.
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Charge-Reversed Exosomes for Targeted Gene Delivery to Cartilage for Osteoarthritis Treatment.电荷反转外泌体用于向软骨靶向递送基因以治疗骨关节炎
Small Methods. 2024 Sep;8(9):e2301443. doi: 10.1002/smtd.202301443. Epub 2024 Apr 12.
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Transcriptomic analysis reveals the anti-cancer effect of gestational mesenchymal stem cell secretome.转录组分析揭示了妊娠期间充质干细胞分泌组的抗癌作用。
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