Journal of Extracellular Vesicles最新文献

{"title":"Direct delivery of immune modulators to tumour-infiltrating lymphocytes using engineered extracellular vesicles","authors":"Xiabing Lyu,&nbsp;Tomoyoshi Yamano,&nbsp;Kanto Nagamori,&nbsp;Shota Imai,&nbsp;Toan Van Le,&nbsp;Dilireba Bolidong,&nbsp;Makie Ueda,&nbsp;Shota Warashina,&nbsp;Hidefumi Mukai,&nbsp;Seigo Hayashi,&nbsp;Kazutaka Matoba,&nbsp;Taito Nishino,&nbsp;Rikinari Hanayama","doi":"10.1002/jev2.70035","DOIUrl":"https://doi.org/10.1002/jev2.70035","url":null,"abstract":"<p>Extracellular vesicles (EVs) are important mediators of cell–cell communication, including immune regulation. Despite the recent development of several EV-based cancer immunotherapies, their clinical efficacy remains limited. Here, we created antigen-presenting EVs to express peptide-major histocompatibility complex (pMHC) class I, costimulatory molecule and IL-2. This enabled the selective delivery of multiple immune modulators to antigen-specific CD8⁺ T cells, promoting their expansion in vivo without severe adverse effects. Notably, antigen-presenting EVs accumulated in the tumour microenvironment, increasing IFN-γ⁺ CD8⁺ T cell and decreasing exhausted CD8⁺ T cell numbers, suggesting that antigen-presenting EVs transformed the ‘cold’ tumour microenvironment into a ‘hot’ one. Combination therapy with antigen-presenting EVs and anti-PD-1 demonstrated enhanced anticancer immunity against established tumours. We successfully engineered humanized antigen-presenting EVs, which selectively stimulated tumour antigen-specific CD8⁺ T cells. In conclusion, engineering EVs to co-express multiple immunomodulators represents a promising method for cancer immunotherapy.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 4","pages":""},"PeriodicalIF":15.5,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70035","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143726850","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":"Dynamic Change of PD-L2 on Circulating Plasma Extracellular Vesicles as a Predictor of Treatment Response in Melanoma Patients Receiving Anti-PD-1 Therapy","authors":"Linzi Sun,&nbsp;Xiaoting Wei,&nbsp;Qian Zhao,&nbsp;Lili Mao,&nbsp;Xue Bai,&nbsp;Caili Li,&nbsp;Junjie Gu,&nbsp;Yan Kong,&nbsp;Chuanliang Cui,&nbsp;Zhihong Chi,&nbsp;Xinan Sheng,&nbsp;Bin Lian,&nbsp;Xuan Wang,&nbsp;Siming Li,&nbsp;Xieqiao Yan,&nbsp;Bixia Tang,&nbsp;Li Zhou,&nbsp;Juan Li,&nbsp;Jun Guo,&nbsp;Lu Si,&nbsp;Jie Dai","doi":"10.1002/jev2.70054","DOIUrl":"https://doi.org/10.1002/jev2.70054","url":null,"abstract":"<p>Immune checkpoint inhibitors (ICIs) have provided new hope for melanoma patients, however, not all patients benefit. Furthermore, ICI-related therapies cause significant immune-related adverse events that adversely affect patient outcomes. Therefore, there is a pressing need for reliable biomarkers to identify patients most likely to benefit from these treatments. In this study, we employed an extracellular vesicles (EVs) protein expression array to explore the longitudinal membrane protein profiles of plasma-derived EVs from 32 melanoma patients receiving anti-PD-1 and anti-angiogenesis therapy at baseline and early treatment. We found that the dynamic changes in PD-L2 on the EV membrane were associated with treatment response and patient survival. The dynamic change of EV PD-L2 as an indication of treatment efficacy was validated in an independent cohort of melanoma patients treated with anti-PD-1 monotherapy. Plasma-derived PD-L2+ EVs from patients with mucosal melanoma significantly reduced the frequency of granzyme B+ CD8 T cells within the peripheral blood mononuclear cells (PBMCs) of healthy individuals. The inhibitory effect of PD-L2+ EVs on CD8 T cells was further validated using human melanoma cell lines and the B16-F10 mouse model. Although intratumoural injection of PD-L2+ EVs could promote melanoma growth in vivo, tumours with PD-L2+ EVs showed a higher response to anti-PD-1 than those without PD-L2+ EVs. Collectively, our study demonstrates that PD-L2+ EVs inhibit CD8 T cell activation and promote melanoma growth, and changes in PD-L2 on circulating EVs during early treatment could serve as a biomarker for ICI-based therapy.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 4","pages":""},"PeriodicalIF":15.5,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70054","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143698865","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":"Nanoscopic Profiling of Small Extracellular Vesicles via High-Speed Atomic Force Microscopy (HS-AFM) Videography","authors":"Muhammad Isman Sandira,&nbsp;Keesiang Lim,&nbsp;Takeshi Yoshida,&nbsp;Elma Sakinatus Sajidah,&nbsp;Shinnosuke Narimatsu,&nbsp;Reon Imakawa,&nbsp;Kota Yoshimura,&nbsp;Goro Nishide,&nbsp;Yujia Qiu,&nbsp;Azuma Taoka,&nbsp;Masaharu Hazawa,&nbsp;Toshio Ando,&nbsp;Rikinari Hanayama,&nbsp;Richard W. Wong","doi":"10.1002/jev2.70050","DOIUrl":"https://doi.org/10.1002/jev2.70050","url":null,"abstract":"<p>Small extracellular vesicles (sEVs), which carry lipids, proteins and RNAs from their parent cells, serve as biomarkers for specific cell types and biological states. These vesicles, including exosomes and microvesicles, facilitate intercellular communication by transferring cellular components between cells. Current methods, such as ultracentrifugation and Tim-4 affinity method, yield high-purity sEVs. However, despite their small size, purified sEVs remain heterogeneous due to their varied intracellular origins. In this technical note, we used high-speed atomic force microscopy (HS-AFM) in conjunction with exosome markers (IgG^CD63 and IgG^CD81) to explore the intracellular origins of sEVs at single-sEV resolution. Our results first revealed the nanotopology of HEK293T-derived sEVs under physiological conditions. Larger sEVs (diameter &gt; 100 nm) exhibited greater height fluctuations compared to smaller sEVs (diameter ≤ 100 nm). Next, we found that mouse-origin IgG^CD63, and rabbit-origin IgG^control and IgG^CD81, exhibited the iconic ‘Y’ conformation, and similar structural dynamics properties. Last, exosome marker antibodies predominantly co-localised with sEV_{d ≤ 100 nm} but not with sEV_{d &gt; 100 nm}, demonstrating the CD63-CD81-enriched sEV and CD63-CD81-depleted sEV subpopulations. In summary, we demonstrate that nanoscopic profiling of surface exosome markers on sEVs using HS-AFM is feasible for characterising distinct sEV subpopulations in a heterogeneous sEV mixture.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 4","pages":""},"PeriodicalIF":15.5,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70050","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707406","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":"MFGE-8, a Corona Protein on Extracellular Vesicles, Mediates Self-Renewal and Survival of Human Pluripotent Stem Cells","authors":"Youngseok Lee,&nbsp;Hyojin Kim,&nbsp;Heeseok Yoon,&nbsp;Seunghyun Cho,&nbsp;Jeongjun Kim,&nbsp;Jihun Lee,&nbsp;Sang-Hun Choi,&nbsp;Hyesun Cho,&nbsp;Dong-Hun Woo,&nbsp;Jung-Hyuck Park,&nbsp;Choongseong Han,&nbsp;Jong-Hoon Kim","doi":"10.1002/jev2.70056","DOIUrl":"https://doi.org/10.1002/jev2.70056","url":null,"abstract":"<p>Extracellular vesicles (EVs) and secretory factors play crucial roles in intercellular communication, but the molecular mechanisms and dynamics governing their interplay in human pluripotent stem cells (hPSCs) are poorly understood. Here, we demonstrate that hPSC-secreted milk fat globule-EGF factor 8 (MFGE-8) is the principal corona protein at the periphery of EVs, playing an essential role in controlling hPSC stemness. MFGE-8 depletion reduced EV-mediated self-renewal and survival in hPSC cultures. MFGE-8 in the EV corona bound to integrin α_vβ₅ expressed in the peripheral zone of hPSC colonies. It activated cyclin D1 and dynamin-1 via the AKT/GSK3β axis, promoting the growth of hPSCs and facilitating the endocytosis of EVs. Internalization of EVs alleviated oxidative stress and cell death by transporting redox and stress response proteins that increased GSH levels. Our findings demonstrate the critical role of the extracellular association of MFGE-8 and EVs in modulating the self-renewal and survival of hPSCs.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 4","pages":""},"PeriodicalIF":15.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70056","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143689782","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":"Circulating Extracellular Vesicles as Putative Mediators of Cardiovascular Disease in Paediatric Chronic Kidney Disease","authors":"Felix Behrens,&nbsp;Johannes Holle,&nbsp;Chia-Yu Chen,&nbsp;Laura F. Ginsbach,&nbsp;Benjamin C. Krause,&nbsp;Ulrike Bruning,&nbsp;Fabian L. Kriegel,&nbsp;Toralf Kaiser,&nbsp;István A. Szijártó,&nbsp;Harithaa Anandakumar,&nbsp;Katrin Lehmann,&nbsp;Fabian Schumacher,&nbsp;Pawel Durek,&nbsp;Frederik F. Heinrich,&nbsp;Dörte Lodka,&nbsp;Carina Hoffmann,&nbsp;André A. Borchardt,&nbsp;Lisa Peters,&nbsp;Laura Michalick,&nbsp;Uwe Querfeld,&nbsp;Philip Bufler,&nbsp;Andreas Luch,&nbsp;Burkhard Kleuser,&nbsp;Jennifer A. Kirwan,&nbsp;Sofia K. Forslund,&nbsp;Julia Thumfahrt,&nbsp;Dominik Müller,&nbsp;Nicola Wilck,&nbsp;Mir-Farzin Mashreghi,&nbsp;Ulrike Löber,&nbsp;Hendrik Bartolomaeus,&nbsp;Wolfgang M. Kuebler,&nbsp;Szandor Simmons","doi":"10.1002/jev2.70062","DOIUrl":"10.1002/jev2.70062","url":null,"abstract":"<p>Cardiovascular disease (CVD) is the leading cause of mortality in chronic kidney disease (CKD). However, the pathogenesis of CVD in CKD remains incompletely understood. Endothelial extracellular vesicles (EC-EVs) have previously been associated with CVD. We hypothesized that CKD alters EV release and cargo, subsequently promoting vascular remodelling. We recruited 94 children with CKD, including patients after kidney transplantation and healthy donors, and performed EV phenotyping and functional EV analyses in the absence of age-related comorbidities. Plasma EC-EVs were increased in haemodialysis patients and decreased after kidney transplantation. Thirty microRNAs were less abundant in total CKD plasma EVs with predicted importance in angiogenesis and smooth muscle cell proliferation. In vitro, CKD plasma EVs induced transcriptomic changes in angiogenesis pathways and functionally impaired angiogenic properties, migration and proliferation in ECs. High shear stress, as generated by arterio-venous fistulas, and uremic toxins were considered as potential drivers of EV release, but only the combination increased EV generation from venous ECs. The resulting EVs recapitulated miRNA changes observed in CKD in vivo. In conclusion, CKD results in the release of EVs with altered miRNA profiles and anti-angiogenic properties, which may mediate vascular pathology in children with CKD. EVs and their miRNA cargo may represent future therapeutic targets to attenuate CVD in CKD.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 3","pages":""},"PeriodicalIF":15.5,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11926757/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674057","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":"Next Generation Aqueous Two-Phase System for Gentle, Effective, and Timely Extracellular Vesicle Isolation and Transcriptomic Analysis","authors":"Boyang Su,&nbsp;Morteza Jeyhani,&nbsp;Gobi Thillainadesan,&nbsp;Minzhi Sheng,&nbsp;Reese Wunsche,&nbsp;Thamara Dayarathna,&nbsp;Kristin Cimolai,&nbsp;Hanyi Weng,&nbsp;Katarzyna J. Jerzak,&nbsp;Stanley K. Liu,&nbsp;Scott S. H. Tsai,&nbsp;Hon S. Leong","doi":"10.1002/jev2.70058","DOIUrl":"10.1002/jev2.70058","url":null,"abstract":"<p>The isolation of extracellular vesicles (EVs) using currently available methods frequently compromises purity and yield to prioritize speed. Here, we present a next-generation aqueous two-phase system (next-gen ATPS) for the isolation of EVs regardless of scale and volume that is superior to conventional methods such as ultracentrifugation (UC) and commercial kits. This is made possible by the two aqueous phases, one rich in polyethylene glycol (PEG) and the other rich in dextran (DEX), whereby fully encapsulated lipid vesicles preferentially migrate to the DEX-rich phase to achieve a local energy minimum for the EVs. Isolated EVs as found in the DEX-rich phase are more amenable to biomarker analysis such as nanoscale flow cytometry (nFC) when using various pre-conjugated antibodies specific for CD9, CD63 and CD81. TRIzol RNA isolation is further enabled by the addition of dextranase, a critical component of this next-gen ATPS method. RNA yield of next-gen ATPS-isolated EVs is superior to UC and other commercial kits. This negates the use of specialized EV RNA extraction kits. The use of dextranase also enables more accurate immunoreactivity of pre-conjugated antibodies for the detection of EVs by nFC. Transcriptomic analysis of EVs isolated using the next-gen ATPS revealed a strong overlap in microRNA (miRNA), circular RNA (circRNA) and small nucleolar RNA (snoRNA) profiles with EV donor cells, as well as EVs isolated by UC and the exoRNeasy kit, while detecting a superior number of circRNAs compared to the kit in human samples. Overall, this next-gen ATPS method stands out as a rapid and highly effective approach to isolate high-quality EVs in high yield, ensuring optimal extraction and analysis of EV-encapsulated nucleic acids.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 3","pages":""},"PeriodicalIF":15.5,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11923243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663451","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":"Toward Identification of Markers for Brain-Derived Extracellular Vesicles in Cerebrospinal Fluid: A Large-Scale, Unbiased Analysis Using Proximity Extension Assays","authors":"Maia Norman,&nbsp;Adnan Shami-shah,&nbsp;Sydney C. D'Amaddio,&nbsp;Benjamin G. Travis,&nbsp;Dmitry Ter-Ovanesyan,&nbsp;Tyler J. Dougan,&nbsp;David R. Walt","doi":"10.1002/jev2.70052","DOIUrl":"https://doi.org/10.1002/jev2.70052","url":null,"abstract":"<p>Extracellular vesicles (EVs) captured in biofluids have opened a new frontier for liquid biopsies. To enrich for vesicles coming from a particular cell type or tumour, scientists utilize antibodies to transmembrane proteins that are relatively unique to the cell type of interest. However, recent evidence has called into question the basic assumption that all transmembrane proteins measured in biofluids are, in fact, EV-associated. To identify both candidate markers for brain-derived EV immunocapture and cargo proteins to validate the EVs’ cell of origin, we conducted an unbiased Olink screen, measuring 5416 unique proteins in cerebrospinal fluid after size exclusion chromatography. We identified proteins that demonstrated a clear EV fractionation pattern and created a searchable dataset of candidate EV-associated markers—both proteins that are cell type-specific within the brain, and proteins found across multiple cell types for use as general EV markers. We further implemented the DeepTMHMM deep learning model to differentiate predicted cytosolic, transmembrane, and external proteins and found that intriguingly, only 10% of the predicted transmembrane proteins have a clear EV fractionation pattern based on our stringent criteria. This dataset further bolsters the critical importance of verifying EV association of candidate proteins using methods such as size exclusion chromatography before downstream use of the targets for EV analysis.</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/jev2.70052","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639018","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":"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}