Real-time monitoring of small extracellular vesicles (sEVs) by in vivo flow cytometry

IF 15.5 1区 医学 Q1 CELL BIOLOGY Journal of Extracellular Vesicles Pub Date : 2024-10-23 DOI:10.1002/jev2.70003
Fuli Zhang, Xin Lu, Xi Zhu, Ziwen Yu, Weiliang Xia, Xunbin Wei
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Abstract

Extracellular vesicles (EVs) are vesicular structures comprised of a bilayer lipid membrane, released by living cells. There is a growing body of evidence for their functionality, indicating that small EVs (sEVs) can mediate specific forms of intercellular communication. The future applications of sEVs hold great promise, not only as diagnostic markers but also as therapeutic agents. However, the greatest difficulty in the clinical translation of sEVs is that they are currently poorly understood, especially concerning their in vivo behaviour. In this study, we provide a novel method for monitoring sEVs in blood circulation based on in vivo flow cytometry (IVFC). We have demonstrated that the height of the IVFC signal baseline is proportional to the concentration of sEVs. Moreover, we have found out that the peaks in the IVFC signal are generated by the aggregation or cellular uptake of sEVs. In vivo monitoring of sEVs clearance from the blood indicates that PEGylated sEVs have a longer residence time and exhibit less aggregation in circulation compared to non-PEGylated sEVs. These studies reveal that IVFC enables real-time in vivo monitoring of circulating sEVs, which can provide valuable insights into the pharmacokinetics and cellular targeting capabilities of sEVs.

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利用体内流式细胞仪实时监测细胞外小泡(sEVs)。
细胞外囊泡(EVs)是由双层脂膜组成的囊泡结构,由活细胞释放。越来越多的证据表明,小EVs(sEVs)可以介导特定形式的细胞间通信,从而证明了它们的功能。sEVs 未来的应用前景广阔,不仅可以作为诊断标志物,还可以作为治疗药物。然而,sEVs 应用于临床的最大困难在于人们目前对其了解甚少,尤其是对其体内行为的了解。在这项研究中,我们提供了一种基于体内流式细胞术(IVFC)监测血液循环中 sEVs 的新方法。我们证明,IVFC 信号基线的高度与 sEVs 的浓度成正比。此外,我们还发现 IVFC 信号的峰值是由 sEVs 的聚集或细胞摄取产生的。对 sEVs 从血液中清除的体内监测表明,与非 PEG 化 sEVs 相比,PEG 化 sEVs 在血液循环中的停留时间更长,聚集程度更低。这些研究表明,IVFC 能够对循环中的 sEVs 进行实时体内监测,从而为了解 sEVs 的药代动力学和细胞靶向能力提供有价值的信息。
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来源期刊
Journal of Extracellular Vesicles
Journal of Extracellular Vesicles Biochemistry, Genetics and Molecular Biology-Cell Biology
CiteScore
27.30
自引率
4.40%
发文量
115
审稿时长
12 weeks
期刊介绍: The Journal of Extracellular Vesicles is an open access research publication that focuses on extracellular vesicles, including microvesicles, exosomes, ectosomes, and apoptotic bodies. It serves as the official journal of the International Society for Extracellular Vesicles and aims to facilitate the exchange of data, ideas, and information pertaining to the chemistry, biology, and applications of extracellular vesicles. The journal covers various aspects such as the cellular and molecular mechanisms of extracellular vesicles biogenesis, technological advancements in their isolation, quantification, and characterization, the role and function of extracellular vesicles in biology, stem cell-derived extracellular vesicles and their biology, as well as the application of extracellular vesicles for pharmacological, immunological, or genetic therapies. The Journal of Extracellular Vesicles is widely recognized and indexed by numerous services, including Biological Abstracts, BIOSIS Previews, Chemical Abstracts Service (CAS), Current Contents/Life Sciences, Directory of Open Access Journals (DOAJ), Journal Citation Reports/Science Edition, Google Scholar, ProQuest Natural Science Collection, ProQuest SciTech Collection, SciTech Premium Collection, PubMed Central/PubMed, Science Citation Index Expanded, ScienceOpen, and Scopus.
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