Journal of extracellular biology最新文献

{"title":"Biomolecular Corona of Extracellular Vesicles: Report on Isev Workshop","authors":"Lucia Paolini,&nbsp;Selene Tassoni,&nbsp;Khuloud T. Al-Jamal,&nbsp;Xavier Banquy,&nbsp;Tamás Beke-Somfai,&nbsp;Paolo Bergese,&nbsp;Fanni Annamária Boros,&nbsp;Massimo Bottini,&nbsp;Ben Boyd,&nbsp;Sara Busatto,&nbsp;Benedetta Bussolati,&nbsp;Ester Canepa,&nbsp;Valentina Castagnola,&nbsp;Aled Clayton,&nbsp;Kenneth Dawson,&nbsp;Samir El-Andaloussi,&nbsp;András Försönits,&nbsp;Orazio Fortunato,&nbsp;Roberto Frigerio,&nbsp;Martina Gabrielli,&nbsp;Cristina Grange,&nbsp;Michele Guescini,&nbsp;Yuya Hayashi,&nbsp;Jonas Klejs Hemmingsen,&nbsp;Seungmin Kim,&nbsp;Ilyes Kinga,&nbsp;Heikki Kyykallio,&nbsp;Metka Lenassi,&nbsp;Luize Goncalves Lima,&nbsp;Mỹ G. Mahoney,&nbsp;Camille Menaceur Vandenbroucke,&nbsp;Andreas Möller,&nbsp;Angelo Musicò,&nbsp;Inge Nelissen,&nbsp;Lucas Fabrício Bahia Nogueira,&nbsp;Christa Nöhammer,&nbsp;Pietro Parisse,&nbsp;Charles Ramassamy,&nbsp;Kelly Cristine Santos Roballo,&nbsp;Anna Salvati,&nbsp;María Sancho-Albero,&nbsp;Ganesh Shelke,&nbsp;Paniz Shirmast,&nbsp;Tasvilla Sonallya,&nbsp;Imola Csilla Szigyártó,&nbsp;Monique A. J. van Eijndhoven,&nbsp;Tapani Viitala,&nbsp;Shan Wang,&nbsp;Yan Yan,&nbsp;Andrea Zendrini,&nbsp;Edit Buzás,&nbsp;Annalisa Radeghieri","doi":"10.1002/jex2.70172","DOIUrl":"10.1002/jex2.70172","url":null,"abstract":"<p>The concept of the “biomolecular corona” (BC) was first introduced to describe the spontaneous absorption of molecules, mainly proteins, onto the surface of synthetic nanoparticles upon exposure to biological fluids. More recently, the same term has been used to describe biomolecules that dynamically interact with the surface of extracellular vesicles (EVs) during their biogenesis, secretion, or upon exposure to intracellular or extracellular milieus, including biological fluids. The EV biomolecular corona is a key determinant of EV identity, shaping their cellular uptake, biodistribution, and functional outcomes in both physiological and pathological contexts. EVs, in contrast to synthetic nanoparticles, introduce distinct challenges and perspectives due to their biological origin, innate heterogeneity, and complex combination of physicochemical and biological properties. To address this evolving topic, the International Society for Extracellular Vesicles (ISEV) organized a dedicated workshop in Brescia, Italy, on 27th to 28th February, 2025. The event gathered selected participants from academia and industry, with expertise spanning synthetic nanomaterials, EVs, biophysics, and translational nanomedicine. The program included keynote lectures, oral presentations, posters, and a series of interactive roundtables structured around fundamentals of the biomolecular corona, EV corona biogenesis and composition, analytical and separation tools and clinical and diagnostic potential applications. This report summarizes the key scientific insights, methodological challenges, conceptual debates, and future perspectives that emerged from the workshop.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"5 8","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13454953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148708800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EV-LYSG101: Extracellular Vesicles Loaded With Lysin LYSG101 for Potent Anti-Staphylococcal Activity","authors":"Dominique B. Hoelzinger,&nbsp;Ava M. Koehler de Celaya,&nbsp;Cheryl E. Myers,&nbsp;Natasha P. Dyal,&nbsp;Christopher F. Saling,&nbsp;Raymond Schuch,&nbsp;Gina A. Suh","doi":"10.1002/jex2.70174","DOIUrl":"10.1002/jex2.70174","url":null,"abstract":"<p>Biofilm-associated staphylococcal infections remain exceptionally difficult to treat due to the presence of resilient staphylococcal biofilms and the limited effectiveness of currently available antibiotics. To combat persistent infections, providers are often forced to use prolonged courses of combination antimicrobial therapies that have significant toxicities with limited effectiveness, leading to increased hospital stays, substantial health care costs and a rise in patient morbidity and mortality. <i>Staphylococcus aureus</i> is a dominant cause of recalcitrant biofilms, for which novel non-antibiotic therapeutics are critically needed. Lysins, a class of protein-based antimicrobials, rapidly kill staphylococci, exhibit potent anti-biofilm activity, have a low propensity of resistance development and synergy with antibiotics. To address this unmet need, we evaluate an extracellular vesicle (EV)-based delivery platform for the engineered anti-staphylococcal lysin LYSG101, designed to improve stability and localization at sites of infection. Initial proof-of-concept work is provided here, demonstrating that human serum-derived EVs can be loaded with LYSG101 to exert a potent in vitro antimicrobial effect against both planktonic and biofilm forms of <i>S. aureus</i>. EV-mediated delivery achieved activity equivalent to free lysin, with additional translational advantages including stability and the potential for sustained intra-articular retention. This work supports further development of the EV-mediated lysin delivery as a broadly applicable antimicrobial platform, with potential future applications in biofilm-associated infections, including prosthetic joint infection (PJI).</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"5 8","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13448156/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148690338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polymicrobial Extracellular Vesicles Reduce the Innate Immune Response of Human Cystic Fibrosis Bronchial Epithelial Cells","authors":"Lily A. Charpentier,&nbsp;Roxanna L. Barnaby,&nbsp;Carolyn T. Roche,&nbsp;Byoung-Kyu Cho,&nbsp;Prashant Kaushal,&nbsp;Young Ah Goo,&nbsp;Brad Vietje,&nbsp;Douglas J. Taatjes,&nbsp;Alix Ashare,&nbsp;Fabrice Jean-Pierre,&nbsp;Bruce A. Stanton","doi":"10.1002/jex2.70176","DOIUrl":"https://doi.org/10.1002/jex2.70176","url":null,"abstract":"<p>Chronic antibiotic-resistant cystic fibrosis (CF) lung infections are the leading cause of death in adults with CF. Despite advances in highly effective modulator therapies, microbial communities persist in the CF lung. The pathogenesis of CF airway infections can be exacerbated by pathogens such as <i>Pseudomonas aeruginosa</i>, which communicates with primary human bronchial epithelial cells (pHBEC) by secreting bacterial extracellular vesicles (bEVs) that diffuse through mucus and deliver virulence factors, DNA, and RNA to pHBEC. However, most CF lung infections are polymicrobial in nature, and therefore, the contribution of polymicrobial bEVs remains to be determined. By using a polymicrobial culture model representing a ‘pulmotype’ detected in ∼34% of lung infections in people with CF (pwCF), comprised of <i>P. aeruginosa</i>, <i>Staphylococcus aureus</i>, <i>Streptococcus sanguinis</i> and <i>Prevotella melaninogenica</i> grown in synthetic sputum medium under anoxia, we report that each bacterial genus in the polymicrobial community secretes bEVs containing proteins and RNAs predicted to promote the establishment of chronic infection by reducing Elexacaftor/Tezacaftor/Ivacaftor (ETI) stimulated CF pHBEC CFTR Cl⁻ secretion, enhancing virulence and biofilm formation, and upregulating the stress response and pro-inflammatory pathways in pHBEC. This response is most pronounced in CF pHBEC. ETI, a highly effective modulator therapy, did not ameliorate the response of CF pHBEC or return it to WT levels. These studies provide insight into why ETI does not eliminate polymicrobial lung infections and a hyperinflammatory lung environment in pwCF.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"5 8","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jex2.70176","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148662293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polymicrobial Extracellular Vesicles Reduce the Innate Immune Response of Human Cystic Fibrosis Bronchial Epithelial Cells","authors":"Lily A. Charpentier,&nbsp;Roxanna L. Barnaby,&nbsp;Carolyn T. Roche,&nbsp;Byoung-Kyu Cho,&nbsp;Prashant Kaushal,&nbsp;Young Ah Goo,&nbsp;Brad Vietje,&nbsp;Douglas J. Taatjes,&nbsp;Alix Ashare,&nbsp;Fabrice Jean-Pierre,&nbsp;Bruce A. Stanton","doi":"10.1002/jex2.70176","DOIUrl":"https://doi.org/10.1002/jex2.70176","url":null,"abstract":"<p>Chronic antibiotic-resistant cystic fibrosis (CF) lung infections are the leading cause of death in adults with CF. Despite advances in highly effective modulator therapies, microbial communities persist in the CF lung. The pathogenesis of CF airway infections can be exacerbated by pathogens such as <i>Pseudomonas aeruginosa</i>, which communicates with primary human bronchial epithelial cells (pHBEC) by secreting bacterial extracellular vesicles (bEVs) that diffuse through mucus and deliver virulence factors, DNA, and RNA to pHBEC. However, most CF lung infections are polymicrobial in nature, and therefore, the contribution of polymicrobial bEVs remains to be determined. By using a polymicrobial culture model representing a ‘pulmotype’ detected in ∼34% of lung infections in people with CF (pwCF), comprised of <i>P. aeruginosa</i>, <i>Staphylococcus aureus</i>, <i>Streptococcus sanguinis</i> and <i>Prevotella melaninogenica</i> grown in synthetic sputum medium under anoxia, we report that each bacterial genus in the polymicrobial community secretes bEVs containing proteins and RNAs predicted to promote the establishment of chronic infection by reducing Elexacaftor/Tezacaftor/Ivacaftor (ETI) stimulated CF pHBEC CFTR Cl⁻ secretion, enhancing virulence and biofilm formation, and upregulating the stress response and pro-inflammatory pathways in pHBEC. This response is most pronounced in CF pHBEC. ETI, a highly effective modulator therapy, did not ameliorate the response of CF pHBEC or return it to WT levels. These studies provide insight into why ETI does not eliminate polymicrobial lung infections and a hyperinflammatory lung environment in pwCF.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"5 8","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jex2.70176","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148662294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Secretion of Extracellular Vesicles Into the Mesenteric Lymph During Fasting and Lipid Absorption","authors":"Tianyu Hang,&nbsp;Rita Wang,&nbsp;Kundanika Mukherjee,&nbsp;Uday Sandhu,&nbsp;Fengxia Xiao,&nbsp;Dylan Burger,&nbsp;Changting Xiao","doi":"10.1002/jex2.70170","DOIUrl":"10.1002/jex2.70170","url":null,"abstract":"<p>The intestine plays critical roles in nutrient homeostasis and systemic health. The small intestine is the major organ that packages dietary lipids into chylomicrons and secretes them into the mesenteric lymph. Extracellular vesicles (EVs) as a mechanism for cell-to-cell communication often exhibit organ specific characteristics. EV secretion from the intestine into the mesenteric lymph—a unique biofluid—remains unexplored. To characterize gut-derived EVs, Sprague-Dawley rats were surgically implanted with cannula in the mesenteric lymph duct (for lymph collection) and the duodenum (for lipid infusion). Lymph fluid was collected for assessment of EV secretion. EVs in lymph fluids collected before and after lipid infusion were characterized by transmission electron microscopy, nanoparticle tracking analysis, and further analyzed by flow cytometry with antibodies against CD63, CD81, CD9 and apolipoprotein B (ApoB). Lipid infusion increased lymph triglyceride output peaking at 2 h. Lymph fluids contained EVs with diameters in the range of 20 to 300 nm and the signals of specific EV markers CD63, CD81 and CD9 were significantly elevated following lipid infusion. Depletion of chylomicrons from lymph had differential effects on the percentage and intensity of CD63, CD81 and CD9. In addition, these EVs exhibited distinct patterns in ApoB⁺ particle population, with the median fluorescence intensity of CD63 and CD81 being significantly higher than that of CD9. To conclude, EVs secreted into the mesenteric lymph could rapidly respond to lipid supply. EVs may bind to and co-secrete with chylomicrons. Finally, gut-derived EVs during active lipid absorption may include multiple subtypes with different affinities to chylomicrons. Collectively, these findings highlight the intestine as an EV secretion organ and the mesenteric lymph as an important biofluid harboring EVs, which opens a new venue for future investigation of biological functions of gut-derived EVs.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"5 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13393292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148581277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular Vesicles in Head and Neck Cancer—A Systematic Review","authors":"Abdallah Swaid,&nbsp;Nadisha Piyarathne,&nbsp;Andrea Holme,&nbsp;David Muirhead,&nbsp;Gabriel Landini,&nbsp;Rasha Abu-Eid","doi":"10.1002/jex2.70164","DOIUrl":"https://doi.org/10.1002/jex2.70164","url":null,"abstract":"<p>Head and neck cancer (HNC) is among the top ten malignancies worldwide and is associated with high morbidity and mortality. Oral potentially malignant disorders (OPMDs) predispose to certain HNCs. Recent studies suggest emerging roles of extracellular vesicles (EVs) in malignant transformation and provide potential in the management of HNC. This systematic review aimed to evaluate the role of EVs in HNC and OPMDs. The systematic review followed PRISMA-2020 guidelines and was registered with PROSPERO. A comprehensive literature search was conducted in five electronic databases (Medline, Scopus, Embase, Cochrane and Web of Science), yielding 3705 initial records. Following de-duplication and independent screening, 237 eligible articles were included. Data extraction was performed by two independent reviewers. Risk of bias was assessed using the Joanna Briggs Institute critical appraisal tools. Thematic analysis with narrative data synthesis was conducted and the results were organised under the following subthemes: EV isolation and characterisation methods, EV role in cancer and OPMDs progression, immune modulation, biomarker potential, and therapeutic applications. Studies included in the review were published between “1985–2025” and showed an accelerated growth in EV research after 2020. Most of the studies relied on traditional isolation and characterisation techniques including ultracentrifugation, transmission electron microscopy and flow cytometry. Most evidence was reported from preclinical studies and demonstrated EVs’ promise as biomarkers for early detection, prognostication, and therapeutic targets. However, the findings also underscored the need for standardised protocols. Current evidence on EVs’ role as drivers of epithelial mesenchymal transition, invasion, immune escape, metabolic reprogramming, and angiogenesis in the pathogenesis of HNC are summarised together with the role of EVs as biomarkers in HNC and potential applications in HNC therapy and therapy resistance. Mechanistic insights into the biological behaviour of EVs in HNC are provided and evidence-based recommendations for future research are proposed in this review.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"5 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jex2.70164","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148467675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human Platelet-Derived Extracellular Vesicles Are Internalized by Human Induced Pluripotent Stem Cell-Derived Neurons Under Control and Hypoxic Conditions","authors":"Venla Harju,&nbsp;Kai Härkönen,&nbsp;Ulla Impola,&nbsp;Saara Laitinen,&nbsp;Susanna Narkilahti","doi":"10.1002/jex2.70168","DOIUrl":"10.1002/jex2.70168","url":null,"abstract":"<p>Ischaemic brain stroke is among the leading causes of death and disability worldwide. However, the current treatments have a limited time window and regeneration potential. Clinically relevant human platelet-derived extracellular vesicles (EVs) offer potential neuroprotective treatment for stroke. Here, the neuronal uptake of carboxyfluorescein succinimidyl ester (CFSE)-labelled EVs was confirmed by confocal imaging and three-dimensional (3D) image analysis with Imaris software. The results showed that human induced pluripotent stem cell (hiPSC)-derived neurons can internalize EVs. We also show the colocalization of EVs with cellular organelles: early endosomes and lysosomes. We used an in vitro human model of stroke to study the effects of hypoxia on neurons. After hypoxia, the activity of the neurons, including spiking and bursting, decreased. However, the activity was restored after 72 h of reperfusion. EVs did not affect neuronal activity acutely, but during long-term follow-up, neurons showed increased activity. Together, our findings provide insights into the effects of platelet-derived EVs on neuronal uptake, morphology and functionality and changes after hypoxic insult in an in vitro human model.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"5 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13364541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148451030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunoaffinity-Based Protocol to Enrich Nervous System Cell-, Lung Alveolar Cell-, and Hepatocyte-Derived Extracellular Vesicles From Human Plasma","authors":"Biancamaria Pierri,&nbsp;Gabriela L. Jackson,&nbsp;Olesia Gololobova,&nbsp;Fang Wang,&nbsp;Erez Eitan,&nbsp;Olga Volpert,&nbsp;Vrinda Kalia,&nbsp;Gissette Reyes-Soffer,&nbsp;Louise C. Laurent,&nbsp;Kenneth W. Witwer,&nbsp;Andrea A. Baccarelli,&nbsp;Haotian Wu","doi":"10.1002/jex2.70171","DOIUrl":"10.1002/jex2.70171","url":null,"abstract":"<p>By preserving molecular information inherited from the source cell, extracellular vesicles (EVs) can serve as biomarkers for tissue health or disease, paving the way for liquid biopsy applications. The enrichment of tissue-specific EVs (TS-EVs) from human biofluids can be challenging due to technical and methodological limitations. Here, we use single and sequential immunoaffinity capture workflows to enrich antigen-specific EVs circulating in human blood. We demonstrate the specificity, efficiency, and consistency of our approach for enriching blood plasma EV subpopulations from the nervous system, alveolar cells and hepatocytes. The enriched subpopulations are characterized by canonical EV features and markers, as well as co-localization of tissue-specific and general markers on the surface. We provide a validated workflow to derive multiple EV subpopulations from circulation, leveraging their promise as informative biomarkers of tissue status and enabling liquid biopsy and biomarker discovery.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"5 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13364545/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148451123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Donor Pooling as an Effective Method to Increase MSC EV Production Without Compromising Therapeutic Potential","authors":"Rebecca Davies,&nbsp;Claire Mennan,&nbsp;Anaïs Makos,&nbsp;Tian Lan,&nbsp;Charlotte Hulme,&nbsp;Mark Platt,&nbsp;Karina Wright,&nbsp;Oksana Kehoe","doi":"10.1002/jex2.70167","DOIUrl":"10.1002/jex2.70167","url":null,"abstract":"<p>Mesenchymal stromal cell extracellular vesicles (MSC EVs) hold great therapeutic potential. Their immunomodulatory abilities make them suitable candidates to treat autoimmune diseases, such as rheumatoid arthritis. However, MSC EV production must be reproducibly scaled to meet the demand of research and therapeutics. To achieve this, four human umbilical cord MSC (UC-MSC) donors were pooled, a method known to generate a large cell source, that averages heterogeneous cell attributes. Upon generating MSC EV enrichments, donor pooling proved advantageous by increasing EV yield, both by increasing particle number and the presence of EV defining characteristics. Protein analysis suggests this could be due to an upregulation of protein transport mechanisms but requires further work to confirm. When applied to an inflammatory model of arthritis, pooled UC-MSC EV enrichments surpassed their parental cells and single donor UC-MSC EV enrichments, in alleviating arthritic pathophysiology, albeit the particle input was doubled since this was normalised by cell number. Therefore, we propose donor pooling as a simple and effective method to generate MSC EV enrichments, with potential to increase EV production without compromising therapeutic efficacy.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"5 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13364544/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148451067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RNY1 Is Heterogeneously Partitioned in Inflamed Airway Fluid and Modulates Pro-Inflammatory Macrophage Transcriptional Programming","authors":"Cherie E. Saffold,&nbsp;Antiana C. Richardson,&nbsp;Heather H. Pua","doi":"10.1002/jex2.70162","DOIUrl":"https://doi.org/10.1002/jex2.70162","url":null,"abstract":"<p>YRNAs are small noncoding RNAs that are abundant in the extracellular space. Prior research has shown that YRNAs are present in most biofluids and that their levels fluctuate during disease. Yet our understanding of YRNA dynamics in the context of biofluid extracellular particles during disease processes is limited. In this study, we found that RNY1, one of two murine YRNAs, increases in airway fluid during allergen-induced lung inflammation and correlates with neutrophil infiltration. Using RNase sensitivity assays and size exclusion chromatography, we determined that airway fluid RNY1 is protected by both EVs and protein-containing structures in distinct extracellular compartments. In contrast, the other murine YRNA, RNY3, is only enriched in BALF EVs, suggesting that RNY1 is uniquely partitioned in heterogeneous extracellular particles. Both EV-enriched and protein-enriched RNY1-containing extracellular compartments were able to program robust pro-inflammatory transcriptional responses in target macrophages. RNY1 contributed to this programming, as macrophages treated with a protein-enriched compartment isolated from <i>RNY1^−/−</i> mice demonstrated lower induction of interferon-associated genes. Together, this study demonstrates that YRNAs are heterogeneously packaged in complex biofluids and contribute to intercellular signalling axes during inflammation.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"5 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jex2.70162","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148386602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}