Journal of Extracellular Vesicles最新文献

{"title":"Potential Role of Menstrual Fluid-Derived Small Extracellular Vesicle Proteins in Endometriosis Pathogenesiss","authors":"Shanti Gurung,&nbsp;Jacqueline Piskopos,&nbsp;Joel Steele,&nbsp;Ralf Schittenhelm,&nbsp;Anup Shah,&nbsp;Fiona L. Cousins,&nbsp;Thomas T. Tapmeier,&nbsp;Caroline E. Gargett","doi":"10.1002/jev2.70048","DOIUrl":"https://doi.org/10.1002/jev2.70048","url":null,"abstract":"<p>Endometriosis, a chronic debilitating disease affects 1 in 7–10 girls and women, who have symptoms of severe chronic pain and subfertility and significantly impacts the overall quality of life. Currently, no effective early diagnostic methods are available for early stages of endometriosis. We used menstrual fluid-derived small extracellular vesicles (MF-sEVs) from women with self-reported endometriosis (laparoscopically diagnosed, <i>n</i> = 8) and self-reported without endometriosis and no painful periods (<i>n</i> = 9). MF-sEVs were separated using differential ultracentrifugation and characterised using nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), Western Blot, flow cytometry, mass-proteomics analysis and functional assays. Spherical-shaped sEVs were identified with a median diameter of ∼120 nm, expressing sEV marker proteins. The MF-sEV proteins were classified as endometrial origin. Over 5000 proteins were identified, ∼77% of which were decreased whilst only 22 proteins (largely comprising immunoglobulins) were increased in endometriosis/MF-sEVs compared to control/MF-sEVs. Decreased proteins were involved in nitrogen compound metabolism, immune response, intracellular signal transduction, regulation of programmed cell death, maintenance of cell polarity and actin cytoskeleton organisation. Flow cytometry demonstrated a significant increase in CD86 expression (immune activation marker) in endometriosis/MF-sEVs. Mesothelial cells showed a significant decrease in cellular resistance and junctional protein expression. MF-sEVs are possible contributors to the pathogenesis of endometriosis and may have the potential for early detection of the disease.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 3","pages":""},"PeriodicalIF":15.5,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70048","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639012","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":"Gut Microbiota-Derived Extracellular Vesicles Influence Alcohol Intake Preferences in Rats","authors":"Macarena Díaz-Ubilla,&nbsp;Aliosha I. Figueroa-Valdés,&nbsp;Hugo E. Tobar,&nbsp;María Elena Quintanilla,&nbsp;Eugenio Díaz,&nbsp;Paola Morales,&nbsp;Pablo Berríos-Cárcamo,&nbsp;Daniela Santapau,&nbsp;Javiera Gallardo,&nbsp;Cristian de Gregorio,&nbsp;Juan Ugalde,&nbsp;Carolina Rojas,&nbsp;Antonia Gonzalez-Madrid,&nbsp;Marcelo Ezquer,&nbsp;Yedy Israel,&nbsp;Francisca Alcayaga-Miranda,&nbsp;Fernando Ezquer","doi":"10.1002/jev2.70059","DOIUrl":"https://doi.org/10.1002/jev2.70059","url":null,"abstract":"<p>Growing preclinical and clinical evidence suggests a link between gut microbiota dysbiosis and problematic alcohol consumption. Extracellular vesicles (EVs) are key mediators involved in bacteria-to-host communication. However, their potential role in mediating addictive behaviour remains unexplored. This study investigates the role of gut microbiota-derived bacterial extracellular vesicles (bEVs) in driving high alcohol consumption. bEVs were isolated from the gut microbiota of a high alcohol-drinking rat strain (UChB rats), either ethanol-naïve or following chronic alcohol consumption and administered intraperitoneally or orally to alcohol-rejecting male and female Wistar rats. Both types of UChB-derived bEVs increased Wistar's voluntary alcohol consumption (three bottle choice test) up to 10-fold (<i>p</i> &lt; 0.0001), indicating that bEVs are able and sufficient to transmit drinking behaviour across different rat strains. Molecular analysis revealed that bEVs administration did not induce systemic or brain inflammation in the recipient animals, suggesting that the increased alcohol intake triggered by UChB-derived bEVs operates through an inflammation-independent mechanism. Furthermore, we demonstrate that the vagus nerve mediates the bEV-induced increase in alcohol consumption, as bilateral vagotomy completely abolished the high drinking behaviour induced by both intraperitoneally injected and orally administered bEVs. Thus, this study identifies bEVs as a novel mechanism underlying gut microbiota-induced high alcohol intake in a vagus nerve-dependent manner.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 3","pages":""},"PeriodicalIF":15.5,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70059","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639022","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 Distinct Molecular Properties and Functions of Small EV Subpopulations Isolated From Human Umbilical Cord MSCs Using Tangential Flow Filtration Combined With Size Exclusion Chromatography","authors":"","doi":"10.1002/jev2.70063","DOIUrl":"https://doi.org/10.1002/jev2.70063","url":null,"abstract":"<p>In the originally-published article, corresponding author Tinghe Wu's affiliation and contact information is incorrect. The correct information is:</p><p>Tinghe Wu⁷</p><p>⁷P.S.K. Biosciences Ltd., Nanjing, China</p><p><b>Correspondence</b></p><p>Tinghe Wu, P.S.K. Biosciences Ltd., Nanjing, China. Email: <span>[email protected]</span></p><p>We apologise for this error.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 3","pages":""},"PeriodicalIF":15.5,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70063","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639017","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":"Extracellular Vesicles Secreted by Cancer-Associated Fibroblasts Drive Non-Invasive Cancer Cell Progression to Metastasis via TGF-β Signalling Hyperactivation","authors":"Adilson Fonseca Teixeira,&nbsp;Yanhong Wang,&nbsp;Josephine Iaria,&nbsp;Peter ten Dijke,&nbsp;Hong-Jian Zhu","doi":"10.1002/jev2.70055","DOIUrl":"https://doi.org/10.1002/jev2.70055","url":null,"abstract":"<p>Metastasis is the leading cause of cancer-related deaths. Cancer-associated fibroblasts (CAFs) are abundant components within the tumour microenvironment, playing critical roles in metastasis. Although increasing evidence supports a role for small extracellular vesicles (sEVs) in this process, their precise contribution and molecular mechanisms remain unclear, compromising the development of antimetastatic therapies. Here, we establish that CAF-sEVs drive metastasis by mediating CAF-cancer cell interaction and hyperactivating TGF-β signalling in tumour cells. Metastasis is abolished by genetically targeting CAF-sEV secretion and consequent reduction of TGF-β signalling in cancer cells. Pharmacological treatment with dimethyl amiloride (DMA) decreases CAFs’ sEV secretion, reduces TGF-β signalling levels in tumour cells and abrogates metastasis and tumour self-seeding. This work defines a new mechanism required by CAFs to drive cancer progression, supporting the therapeutic targeting of EV trafficking to disable the driving forces of metastasis.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 3","pages":""},"PeriodicalIF":15.5,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70055","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639100","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":"Unravelling the Significance of Extracellular Vesicle-Associated DNA in Cancer Biology and Its Potential Clinical Applications","authors":"Jamal Ghanam,&nbsp;Kristína Lichá,&nbsp;Venkatesh Kumar Chetty,&nbsp;Ommolbanin Asad Pour,&nbsp;Dirk Reinhardt,&nbsp;Barbora Tamášová,&nbsp;Peter Hoyer,&nbsp;Jan Lötvall,&nbsp;Basant Kumar Thakur","doi":"10.1002/jev2.70047","DOIUrl":"https://doi.org/10.1002/jev2.70047","url":null,"abstract":"<p>Extracellular vesicles (EVs) play a key role in cell-to-cell communication and have drawn significant attention due to their potential clinical applications. However, much remains to be understood about the biology of EV-associated DNA (EV-DNA). EV-DNA is actively released by both normal and malignant cells and consists of diverse fragments with varying structures. Because EV-DNA spans the entire genome of cells from which it originates, it continues to be attractive as a biomarker for cancer diagnosis and monitoring. Further, EV-DNA delivery can alter the function of recipient cells by interfering with cytoplasmic DNA sensor pathways. This review explores the biology and significance of EV-DNA, including its topology and fragmentomics features, modality of association with EVs, packaging mechanisms, and potential functions. It also emphasizes the specificity of vesicular DNA in identifying genetic and epigenetic changes in cancer. Additionally, it delves into the impact of EV-DNA on cellular behaviour and its potential use as a therapeutic target in cancer. The review discusses new insights into EV-DNA biology and provides perspectives and alternatives to address the challenges and concerns for future EV-DNA studies.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 3","pages":""},"PeriodicalIF":15.5,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70047","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639097","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":"Quantitative Lipid Analysis of Extracellular Vesicle Preparations: A Perspective","authors":"Tore Skotland,&nbsp;Kim Ekroos,&nbsp;Alicia Llorente,&nbsp;Kirsten Sandvig","doi":"10.1002/jev2.70049","DOIUrl":"https://doi.org/10.1002/jev2.70049","url":null,"abstract":"<p>Quantitative lipidomic analysis performed by mass spectrometry is required for determination of the lipid content of extracellular vesicles (EVs). Such methods can provide information about the total amount of lipids, the lipid species composition, the purity of EV samples as well as the cellular origin of the EVs. There are, however, many pitfalls when performing lipid analyses. Thus, any non-specialist should collaborate with experts in lipidomics. In addition to many good review articles giving advice about lipid analyses, we recommend the information and guidelines published by the Lipidomic Standard Initiative, an interest group affiliated with the International Lipidomics Society.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 3","pages":""},"PeriodicalIF":15.5,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70049","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639096","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":"Human Transmembrane Serine Protease 2 (TMPRSS2) on Human Seminal Fluid Extracellular Vesicles Is Proteolytically Active","authors":"Emile Verhulst,&nbsp;Michelle De Bruyn,&nbsp;Pascale Berckmans,&nbsp;Yani Sim,&nbsp;Koen Augustyns,&nbsp;Isabel Pintelon,&nbsp;Maya Berg,&nbsp;Pieter Van Wielendaele,&nbsp;Anne-Marie Lambeir,&nbsp;Yann G.-J. Sterckx,&nbsp;Inge Nelissen,&nbsp;Ingrid De Meester","doi":"10.1002/jev2.70061","DOIUrl":"https://doi.org/10.1002/jev2.70061","url":null,"abstract":"<p>Human transmembrane serine protease 2 (TMPRSS2) has garnered substantial interest due to its clinical significance in various pathologies, notably its pivotal role in viral entry into host cells. The development of effective strategies to target TMPRSS2 is a current area of intense research and necessitates a consistent source of active TMPRSS2 with sufficient stability. Here, we comprehensively characterised human seminal-fluid extracellular vesicles (SF-EVs, also referred to as prostasomes), bearing a native source of surface-exposed, enzymatically active TMPRSS2 as demonstrated by high-sensitivity flow cytometry and a fluorometric activity assay. Additionally, we recombinantly produced human TMPRSS2 ectodomain in mammalian cells adopting a directed activation strategy. We observed comparable catalytic parameters and inhibition characteristics for both native SF-EV-associated and recombinant TMPRSS2 when exposed to serine protease inhibitor Nafamostat mesylate. Leveraging these findings, we developed a robust in vitro biochemical assay based on these SF-EVs for the screening of TMPRSS2-targeting compounds. Our results will accelerate the discovery and advancement of efficacious therapeutic approaches targeting TMPRSS2 and propel further exploration into the biological role of SF-EV-associated active TMPRSS2.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 3","pages":""},"PeriodicalIF":15.5,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70061","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639095","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":"Effects of Hydrogels on Mesenchymal Stem/Stromal Cells Paracrine Activity and Extracellular Vesicles Production","authors":"Oscar Fabian Garcia-Aponte,&nbsp;Simon Kahlenberg,&nbsp;Dimitrios Kouroupis,&nbsp;Dominik Egger,&nbsp;Cornelia Kasper","doi":"10.1002/jev2.70057","DOIUrl":"https://doi.org/10.1002/jev2.70057","url":null,"abstract":"<p>Mesenchymal stem/stromal cells (MSCs) are a valuable source of paracrine factors, as they have a remarkable secretory capacity, and there is a sizeable knowledge base to develop industrial and clinical production protocols. Promising cell-free approaches for tissue regeneration and immunomodulation are driving research towards secretome applications, among which extracellular vesicles (EVs) are steadily gaining attention. However, the manufacturing and application of EVs is limited by insufficient yields, knowledge gaps, and low standardization. Facing these limitations, hydrogels represent a versatile three-dimensional (3D) culture platform that can incorporate extracellular matrix (ECM) components to mimic the natural stem cell environment in vitro; via these niche-mimicking properties, hydrogels can regulate MSCs’ morphology, adhesion, proliferation, differentiation and secretion capacities. However, the impact of the hydrogel's architectural, biochemical and biomechanical properties on the production of EVs remains poorly understood, as the field is still in its infancy and the interdependency of culture parameters compromises the comparability of the studies. Therefore, this review summarizes and discusses the reported effects of hydrogel encapsulation and culture on the secretion of MSC-EVs. Considering the effects of cell-material interactions on the overall paracrine activity of MSCs, we identify persistent challenges from low standardization and process control, and outline future paths of research, such as the synergic use of hydrogels and bioreactors to enhance MSC-EV generation.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 3","pages":""},"PeriodicalIF":15.5,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70057","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639099","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":"Mechanism of Centrosomal Protein 55 (CEP55) Loading Into Exosomes","authors":"Christian Dahlstroem,&nbsp;Johanna Barezani,&nbsp;Jing Li,&nbsp;Kostiantyn Sopelniak,&nbsp;Stefanie Muhs,&nbsp;Carola Schneider,&nbsp;Roland Thünauer,&nbsp;Rudolph Reimer,&nbsp;Sabine Windhorst","doi":"10.1002/jev2.70046","DOIUrl":"https://doi.org/10.1002/jev2.70046","url":null,"abstract":"<p>Up-regulation of Centrosomal Protein 55 (CEP55) in cancer cells increases malignancy, and the protein can be transferred via exosomes. However, the mechanism of how CEP55 is delivered to exosomes is unknown. In this study, we addressed this issue and analysed trafficking of EGFP-CEP55 from early to late endosomes by using high-resolution microscopy. Our data show that endogenous as well as EGFP-CEP55 appeared as dot-like structures in cancer cells. However, we did not find an internalization of CEP55 into early Rab5- and late Rab7-positive endosomes but only into secretory late CD63-positive endosomes. In addition, an association of the CEP55 dots with the endoplasmic reticulum and with ALG-2-interacting protein X (Alix) dots was detected. Moreover, mutation of the CEP55-Alix interaction site strongly reduced the formation of CEP55 dots as well as CEP55 localization in extracellular vesicles. In summary, our data indicate that delivery of CEP55 into exosomes does not occur by the canonical early-to-late endosome pathway but by Alix-mediated recruitment to secretory late secretory CD63 endosomes.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 2","pages":""},"PeriodicalIF":15.5,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70046","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447011","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":"Extracellular Histones as Exosome Membrane Proteins Regulated by Cell Stress","authors":"Birendra Singh,&nbsp;Marcus Fredriksson Sundbom,&nbsp;Uma Muthukrishnan,&nbsp;Balasubramanian Natarajan,&nbsp;Stephanie Stransky,&nbsp;André Görgens,&nbsp;Joel Z. Nordin,&nbsp;Oscar P. B. Wiklander,&nbsp;Linda Sandblad,&nbsp;Simone Sidoli,&nbsp;Samir El Andaloussi,&nbsp;Michael Haney,&nbsp;Jonathan D. Gilthorpe","doi":"10.1002/jev2.70042","DOIUrl":"https://doi.org/10.1002/jev2.70042","url":null,"abstract":"<p>Histones are conserved nuclear proteins that function as part of the nucleosome in the regulation of chromatin structure and gene expression. Interestingly, extracellular histones populate biofluids from healthy individuals, and when elevated, may contribute to various acute and chronic diseases. It is generally assumed that most extracellular histones exist as nucleosomes, as components of extracellular chromatin. We analysed cell culture models under normal and stressed conditions to identify pathways of histone secretion. We report that core and linker histones localize to extracellular vesicles (EVs) and are secreted via the multivesicular body/exosome pathway. Upregulation of EV histone secretion occurs in response to cellular stress, with enhanced vesicle secretion and a shift towards a population of smaller EVs. Most histones were membrane associated with the outer surface of EVs. Degradation of EV-DNA did not impact significantly on EV-histone association. Individual histones  and histone octamers bound strongly to liposomes and EVs, but nucleosomes did not, showing histones do not require DNA for EV binding. Histones colocalized to tetraspanin positive EVs but using genetic or pharmacological intervention, we found that all known pathways of exosome biogenesis acted positively on histone secretion. Inhibition of autophagy and lysosomal degradation had a strong positive effect on EV histone release. Unexpectedly, EV-associated histones lacked the extensive post-translational modification of their nuclear counterparts, suggesting loss of PTMs may be involved in their trafficking or secretion. Our data does not support a significant role for EV-histones existing as nucleosomes. We show for the first time that histones are secreted from cells as membrane proteins via EVs/exosomes. This fundamental discovery provides support for further investigation of the biological activity of exosome associated histones and their role in disease.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 2","pages":""},"PeriodicalIF":15.5,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70042","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143446659","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}