Journal of Extracellular Vesicles最新文献

{"title":"Bacterial Extracellular Vesicles Exploit Filopodial Surfing and Retraction Mechanisms to Reach the Host Cell Body in an Actin-Dependent Manner","authors":"Zia Ur Rehman,&nbsp;Ikenna Obi,&nbsp;Aftab Nadeem,&nbsp;Nicole Tegtmeyer,&nbsp;Steffen Backert,&nbsp;Anna Arnqvist","doi":"10.1002/jev2.70107","DOIUrl":"https://doi.org/10.1002/jev2.70107","url":null,"abstract":"<p>Extracellular vesicles derived from gram-negative bacteria are nano-sized particles of different size and origin released by these microbes and are collectively called bacterial extracellular vesicles (BEVs). These BEVs may serve as vehicles for delivering bacterial molecules to eukaryotic host cells. Depending on the bacterial species, BEVs elicit various host cellular and immunomodulatory responses, often aiding bacterial survival and communication. Early events in the initial interaction between BEVs and the host cell, as well as how BEVs reach the cell body, remain unexplored. In this study, we describe the interaction of BEVs with actin-rich cellular extensions, including filopodia and retraction fibres, which extend from the host cell surface. Using microscopy-based tracking at the single cell level, BEVs were shown to exploit cellular extensions at the cell periphery to reach the main cell body, either by hijacking retracted extensions or by surfing along these extensions in an actin-dependent manner. BEVs bind to the outer surface of the extensions, but no internalization occurs at this stage. Instead, they serve as transport for BEVs to the main cell body, where endocytosis takes place. Importantly, this process appears to be a general phenomenon for BEVs across different bacterial species and cell origins.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 6","pages":""},"PeriodicalIF":15.5,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70107","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First-In-Human Application of Human Umbilical Cord-Derived Extracellular Vesicles in Tethered Spinal Cord Release Surgery","authors":"Matthias Krause,&nbsp;Janina Gburek-Augustat,&nbsp;Daniel Gräfe,&nbsp;Roman Metzger,&nbsp;Marco Ginzel,&nbsp;Christoph J. Griessenauer,&nbsp;Lukas Grassner,&nbsp;Daniel Weghuber,&nbsp;Johann Gradl,&nbsp;Daniela Auer,&nbsp;Tanja Schally,&nbsp;Stefan Rund,&nbsp;Carina Kals,&nbsp;Christina Folie,&nbsp;Elisabeth Bayer,&nbsp;Mario Gimona,&nbsp;Eva Rohde","doi":"10.1002/jev2.70104","DOIUrl":"https://doi.org/10.1002/jev2.70104","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Spina bifida is a congenital neural tube defect that has a high risk of secondary neurological deterioration due to tethering of the spinal cord. We present the first application of human umbilical cord-derived mesenchymal stromal cell-derived extracellular vesicle (UC-MSC-EV) therapy in humans during spina bifida surgery. We discuss the application, post-operative outcome and highlight the potential of extracellular vesicle therapy in the management of spina bifida.</p>\u0000 \u0000 <p>Administration of extracellular vesicles containing therapeutically active agents has emerged as a potential new treatment modality for neurological disorders. By direct intrathecal application during surgery, UC-MSC-EVs can deliver therapeutic payloads to target cells and the extracellular environment, offering a novel approach to neuroprotection and tissue repair.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <p>A 2-year-old girl diagnosed with spina bifida presented with progressive syringomyelia as sign of secondary tethered cord syndrome with intramedullary dermoid inclusion tumour after postnatal spina bifida repair. After pre-operative assessment and multidisciplinary consultation, it was decided to proceed with spinal cord release surgery with the use of EV. During the surgical procedure, the tethered cord was released, dermoid and lipoma tissue were resected. Concurrently, UC-MSC-EVs were administered directly onto the released placode and spinal cord. Post-operative MRI demonstrated a good de-tethering effect and no medullary oedema. No adverse events were reported. The neurological deficit remained unchanged at 6 months follow-up examination.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <p>Intraoperative application of UC-MSC-EVs might be an option to ameliorate intrathecal scarring following spina bifida surgery. Whether EVs will result in significant effects for the long-term neurological outcome needs to be studied in randomised clinical trials.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 6","pages":""},"PeriodicalIF":15.5,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70104","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144323426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineering of CD63 Enables Selective Extracellular Vesicle Cargo Loading and Enhanced Payload Delivery","authors":"Wataru Obuchi,&nbsp;Ayrton Zargani-Piccardi,&nbsp;Kevin Leandro,&nbsp;David Rufino-Ramos,&nbsp;Emilio Di lanni,&nbsp;Dawn Madison Frederick,&nbsp;Katia Maalouf,&nbsp;Lisa Nieland,&nbsp;Tianhe Xiao,&nbsp;Pierre Repiton,&nbsp;Christine A. Vaine,&nbsp;Benjamin P. Kleinstiver,&nbsp;D. Cristopher Bragg,&nbsp;Hakho Lee,&nbsp;Miles A. Miller,&nbsp;Xandra O. Breakefield,&nbsp;Koen Breyne","doi":"10.1002/jev2.70094","DOIUrl":"https://doi.org/10.1002/jev2.70094","url":null,"abstract":"<p>Extracellular vesicles (EVs) are mediators of intercellular communication through the transfer of nucleic acids, lipids and proteins between cells. This property makes bioengineered EVs promising therapeutic vectors. However, it remains challenging to isolate EVs with a therapeutic payload due to the heterogeneous nature of cargo loading into EVs. In this study, enrichment of EVs with a desired cargo was possible through engineering of the hallmark CD63 transmembrane protein. E-NoMi refers to engineered CD63 with mCherry on the inside of the EV membrane and a tag (3xFLAG) exposed on the outside of the EV membrane. To facilitate EV loading during biogenesis, cargo proteins, such as EGFP, Cre recombinase and the CRISPR-Cas nuclease (SaCas9), were fused to a nanobody (Nb) protein with a high affinity for mCherry. FLAG-tag-based immunocapture from cell conditioned media allowed selection of cargo-loaded E-NoMi-EVs, and tobacco etch virus (TEV) protease cleavage sites were used to remove the 3xFLAG-tag from the surface of E-NoMi-EVs after capture. For functional payload delivery to recipient cells, the vesicular stomatitis virus G (VSV-G) fusogenic protein was incorporated into E-NoMi-EVs to form fusogenic EV-based vectors (EVVs) and proved to be 10-fold more effective at cargo delivery than EVs generated by size-exclusion chromatography. Functional delivery of cargo with E-NoMi-EVVs was validated in two mouse brain models in vivo.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 6","pages":""},"PeriodicalIF":15.5,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70094","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144308731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-Cell Analysis Reveals Fibroblast-Derived Migrasomes as CXCL12 Carriers Promoting Skin Wound Repair","authors":"Haoyu Zhou,&nbsp;Zhen Zhang,&nbsp;Zhan Liu,&nbsp;Guodong Sa,&nbsp;Mingjing Jiang,&nbsp;Zhongyang Zou,&nbsp;Yingliang Shi,&nbsp;Liwu Zheng,&nbsp;Xuewen Yang,&nbsp;Guoliang Sa","doi":"10.1002/jev2.70112","DOIUrl":"https://doi.org/10.1002/jev2.70112","url":null,"abstract":"<p>Migrasomes are newly discovered organelles with demonstrated functions in organ morphogenesis and angiogenesis. However, the effect of migrasomes in tissue repair remains unreported. Our super-resolution confocal microscopy and focused ion beam scanning electron microscopy results confirmed that migrasomes were directly connected with retraction fibres and could release their contents into the surroundings in human and rat skins and oral mucosae. Multiplex immunofluorescence staining results revealed that these retraction fibres and migrasomes originated from fibroblasts. Live-cell imaging demonstrated that human oral mucosal fibroblast-derived migrasomes could be taken up by both fibroblasts and HaCaT cells. In addition, the injection of purified fibroblast-derived migrasomes into the edges of rat skin wounds significantly accelerated wound healing. Single-cell sequencing results suggested that the clusters of keratinocytes, fibroblasts, and endothelial cells play key roles in the wound-healing process. Moreover, the expression of <i>Vegfa</i>, <i>Il-6</i>, and <i>Col1a1</i> in the fibroblast subcluster was significantly upregulated. Furthermore, these purified migrasomes increased the protein levels of VEGFA, IL-6, and COL1A1 in cultured fibroblasts in vitro. Mechanistically, migrasomes may facilitate wound healing by delivering CXCL12. Thus, our research revealed that fibroblast-derived migrasomes are potential therapeutic vesicles for skin wound-healing repair.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 6","pages":""},"PeriodicalIF":15.5,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70112","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144308682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting Oncofoetal Chondroitin Sulphate Allows Identification of Tumour-Derived Extracellular Vesicles","authors":"Agustin Enciso-Martinez,&nbsp;Caroline Løppke,&nbsp;Joyce J. Koene,&nbsp;Jade Ebbelaar,&nbsp;Meike van der Geest,&nbsp;Mandy Los,&nbsp;Emma P. E. M. Boerrigter,&nbsp;Robert Dagil,&nbsp;Tobias Gustavsson,&nbsp;Elena E. Vidal-Calvo,&nbsp;Ton G. van Leeuwen,&nbsp;Roman I. Koning,&nbsp;Nick van Es,&nbsp;Ali Salanti,&nbsp;Edwin van der Pol,&nbsp;Rienk Nieuwland,&nbsp;Mette Ø. Agerbæk,&nbsp;Peter ten Dijke","doi":"10.1002/jev2.70106","DOIUrl":"https://doi.org/10.1002/jev2.70106","url":null,"abstract":"<p>Tumour-derived extracellular vesicles (tdEVs) are widely studied for their contribution to tumour progression and metastasis. These studies are hampered by the lack of specific markers to identify the tdEVs. Here, we show that oncofoetal chondroitin sulphate, a malignancy-associated glycosaminoglycan modification, is present on tdEVs and can be targeted by the malaria VAR2CSA protein or C9 antibody. Using a fluorescently labelled recombinant VAR2CSA protein, we identified EVs from cancer cells in vitro by super-resolution fluorescence microscopy and flow cytometry, as well as in a proof-of-concept study using plasma samples from pancreatic adenocarcinoma patients. Thus, the binding of VAR2CSA offers a tool to identify tdEVs, and can be used to explore their function and biomarker potential in cancer.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 6","pages":""},"PeriodicalIF":15.5,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70106","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144308681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methods and Challenges in Purifying Drug-Loaded Extracellular Vesicles","authors":"Marie Auquière,&nbsp;Giulio G. Muccioli,&nbsp;Anne des Rieux","doi":"10.1002/jev2.70097","DOIUrl":"https://doi.org/10.1002/jev2.70097","url":null,"abstract":"<p>Extracellular vesicles (EV) have emerged as promising nanocarriers for drug delivery. However, the efficient loading of therapeutic molecules into EV and the subsequent purification of drug-loaded EV from unloaded drugs remain significant challenges. This review explores the most used methods for EV purification, meaning the separation of drug-loaded EV from unloaded drugs, including ultracentrifugation, density gradient centrifugation, ultrafiltration, size exclusion chromatography, dialysis and commercial exosome isolation kits. The principles, advantages and limitations of each method are discussed. Critical parameters such as molecular weight cutoff, membrane composition, and the nature of the loaded molecule are highlighted for their impact on the purification process. The review also addresses the technical aspects, including time, cost and equipment requirements, and emphasizes the need for standardized guidelines to improve reproducibility and comparability across studies. By providing a comprehensive overview of current purification strategies, this review aims to guide researchers in selecting the most appropriate methods for advancing EV-based drug delivery systems.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 6","pages":""},"PeriodicalIF":15.5,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70097","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144308680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced Early Detection of Colorectal Cancer via Blood Biomarker Combinations Identified Through Extracellular Vesicle Isolation and Artificial Intelligence Analysis","authors":"Bonhan Koo,&nbsp;Young Il Kim,&nbsp;Minju Lee,&nbsp;Seok-Byung Lim,&nbsp;Yong Shin","doi":"10.1002/jev2.70088","DOIUrl":"https://doi.org/10.1002/jev2.70088","url":null,"abstract":"<p>Colorectal cancer (CRC) remains a major cause of cancer-related deaths worldwide, with early detection being crucial for improving survival rates. Despite the potential of extracellular vesicles (EVs) as blood biomarkers for CRC diagnosis, their clinical utility is limited due to complex and time-consuming isolation methods, unverified biomarkers and low diagnostic performance. Here, we introduce the ZAHV-AI system, which combines the zeolite-amine and homobifunctional hydrazide-based extracellular vesicle isolation (ZAHVIS) platform with AI-driven analysis for enhanced CRC diagnosis. The ZAHVIS platform enables simple, rapid and cost-effective EV isolation and one-step extraction of EV-derived proteins and nucleic acids (NAs), providing a streamlined approach. Using blood plasma samples from 80 CRC patients across all stages and 20 healthy individuals, we identified four EV-derived miRNA blood biomarkers (miR-23a-3p, miR-92a-3p, miR-125a-3p and miR-150-5p) by confirming statistical significance with relative quantification (RQ) values from real-time PCR and integrated these with carcinoembryonic antigen (CEA) levels into an AI-driven diagnostic model. Among 31 combinations used to identify optimal sets, optimal combination (miR-23a-3p, miR-92a-3p, miR-150-5p and CEA) for overall CRC achieved an area under the curve (AUC) of 0.9861, outperforming individual markers and conventional CEA tests. Notably, the system achieved perfect performance in detecting stages 0–1 (AUC: 1.0) and demonstrated high accuracy for stage 2 (AUC: 0.9722) and early-stage CRC (AUC: 0.9861), using stage-specific optimal combinations. Therefore, the ZAHV-AI system offers a reliable and clinically relevant tool for CRC diagnostics, significantly enhancing early detection and monitoring capabilities.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 6","pages":""},"PeriodicalIF":15.5,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70088","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144273554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to “Synthetic Biology-Based Bacterial Extracellular Vesicles Displaying BMP-2 and CXCR4 to Ameliorate Osteoporosis”","authors":"","doi":"10.1002/jev2.70095","DOIUrl":"https://doi.org/10.1002/jev2.70095","url":null,"abstract":"<p>H. Liu, P. Song, H. Zhang, et al., “Synthetic Biology-Based Bacterial Extracellular Vesicles Displaying BMP-2 and CXCR4 to Ameliorate Osteoporosis,” <i>Journal of Extracellular Vesicles</i> 13 (2024): e12429, https://doi.org/10.1002/jev2.12429.</p><p>In Table 1 of the originally published article, the Characteristic of ECN, “Escherichia coli Nissle 1917,” is incorrect. This should read “<i>Escherichia coli</i> Nissle 1917 carrying the DE3 phage encoding for T7-RNA Polymerase.”</p><p>In addition, Figure 2g in the originally published article is incorrect. The correct figure is shown below.</p><p></p><p>We apologize for this error.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 6","pages":""},"PeriodicalIF":15.5,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70095","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144190950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reflecting on 2100 Days at the Helm of Journal of Extracellular Vesicles: A Thank You Editorial","authors":"Jan Lötvall","doi":"10.1002/jev2.70096","DOIUrl":"https://doi.org/10.1002/jev2.70096","url":null,"abstract":"&lt;p&gt;As I have stepped down as Editor-in-Chief of the &lt;i&gt;Journal of Extracellular Vesicles (JEV)&lt;/i&gt; on April 30th, 2025, exactly 2100 days after assuming the role on August 1st, 2019, I find myself reflecting on the extraordinary journey of growth and increased understanding of EV biology, that I have had the honour to share with many others within the extracellular vesicle (EV) community. Leading this journal has been one of the most rewarding experiences of my scientific career, and I am deeply grateful to the authors, the editorial team, reviewers and our readers who have contributed to its growth and success.&lt;/p&gt;&lt;p&gt;When I took on this role, the field of EV research, and &lt;i&gt;JEV&lt;/i&gt;, was in a rapidly expanding phase, and the journal had just months prior received its first impact factor. However, during the past 5 years, the growth of the field and the journal is further accelerating, and we have experienced a deepened understanding of EV biology, in parallel with technological advancements in both the isolation and characterisation of EVs. &lt;i&gt;JEV&lt;/i&gt; has, from its first inception in 2012, been at the forefront of these developments, publishing groundbreaking studies that have shaped the discourse and pushed the boundaries of our discipline, and is still on a rapidly growing trajectory.&lt;/p&gt;&lt;p&gt;Employing Sarah has, without question, been the most important improvement in the journal's management in the last 5 years, as she professionally manages and oversees the journal, far beyond the scope of what part-time Editors are capable of. Thank you for joining JEV Sarah!&lt;/p&gt;&lt;p&gt;The journal would not be what it is without the dedication of our editorial team, the rigor of our peer reviewers, as well as the trust of the scientific community that submit their work to the journal. Before the employment of Sarah Williams, I have for some periods had the administrative editorial support of several well-established researchers in the field, including Cecilia Lässer and Deborah Goberdhan. In addition, the crucial role of the Deputy Editors as well as Associate Editors in further scrutinising submissions, is essential for any journal. During my tenure, I have had the support of multiple Deputy Editors, including Simon Powis, Esther Nolte-‘t Hoen, Hubert Yin, Mary Bebawy, Michael Freeman, Roosmarijn Vandenbroucke, Yong Song Gho, An Hendrix, and recently also Cherie Blenkrion, Simon Swift, Owen Davis and Dolores Di Vizio, and a broad group of Associate Editors. As EiC, I implemented a multi-step approach to assessing manuscripts, requiring at least two pairs of eyes evaluating a manuscript before the journal declines consideration of a submission, and multiple other assessments by Editors and Reviewers before any work is found acceptable for publication. To retain a reasonable and fair assessment of submissions, I have worked under the principle that one person should be at the helm of the journal, implementing one clear editorial vision for which work is suitable ","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 6","pages":""},"PeriodicalIF":15.5,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70096","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144190949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glutamatergic Regulation of miRNA-Containing Intraluminal Vesicle Trafficking and Extracellular Vesicle Secretion From Cortical Neurons","authors":"Marcela Bertolio,&nbsp;Qiyi Li,&nbsp;Francesca E. Mowry,&nbsp;Kathryn E. Reynolds,&nbsp;Rashed Alananzeh,&nbsp;Haichao Wei,&nbsp;Kyoeun Keum,&nbsp;Rachel Jarvis,&nbsp;Jiaqian Wu,&nbsp;Yongjie Yang","doi":"10.1002/jev2.70100","DOIUrl":"https://doi.org/10.1002/jev2.70100","url":null,"abstract":"<p>Neuronal extracellular vesicles (microvesicles and exosomes) are emerging secreted vesicular signals that play important roles in the CNS. Currently, little is known about how glutamatergic signalling affects the subcellular localisation of exosome precursor intraluminal vesicles (ILVs), microRNA (miR) packaging into ILVs and in vivo spreading of neuronal EVs. By selectively labelling ILVs and exosomes (but not plasma membrane-derived MVs) with GFP-tagged human CD63 (hCD63-GFP) in cortical neurons, we found that glutamate stimulation significantly redistributes subcellular localisation of hCD63-GFP⁺ ILVs, especially decreasing its co-localisation with multi-vesicular body (MVB) marker Rab7 while substantially promoting EV secretion. Interestingly, glutamate stimulation only modestly alters EV miR profiles based on small RNA sequencing. Subsequent in vivo cortical neuronal DREADD activation leads to significantly more widespread hCD63-GFP⁺ area in hCD63-GFP^f/+ mice, consistently supporting the stimulatory effect of glutamatergic activation on neuronal EV secretion and spreading. Moreover, in situ localisation of hCD63-GFP⁺ ILVs and hCD63-GFP⁺ secreted exosomes from specialised HB9⁺ and DAT⁺ neurons were also illustrated in the CNS. Taken together, our results demonstrated that glutamate activity stimulates neuronal exosome secretion and spreading in vitro and in vivo, but only modestly affects miR cargo packaging in neuronal exosomes.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 6","pages":""},"PeriodicalIF":15.5,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70100","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144171946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}