Journal of extracellular biology最新文献

{"title":"Senescent Cell-Derived Extracellular Vesicles in Therapy-Induced Senescence: Immune Remodelling and Emerging Links to Mitochondrial Stress in Cancer","authors":"Yongrui Qian,&nbsp;Zirui Weng,&nbsp;Na Li,&nbsp;Yun Zhou,&nbsp;Hailong Pei","doi":"10.1002/jex2.70193","DOIUrl":"https://doi.org/10.1002/jex2.70193","url":null,"abstract":"<p>Cancer therapy can induce cellular senescence and remodel the tumour microenvironment through the senescence-associated secretory phenotype (SASP), including its membrane-enclosed component, senescent cell-derived extracellular vesicles (senEVs). This review summarizes senEV biogenesis, cargo-dependent functions, and immune-remodelling effects while distinguishing mechanisms directly demonstrated in experimentally validated senescent-cell EV models from contextual evidence derived from broader EV and mitochondrial-stress studies. Direct evidence shows that senEVs can support immune-mediated clearance in some models or promote tumour growth, chemoresistance, and polymorphonuclear myeloid-derived suppressor cell (PMN-MDSC)-mediated immunosuppression in others. We further evaluate mitochondrial stress and EV-associated mitochondrial DNA as an emerging mechanistic framework that may contribute to these divergent outcomes, rather than as an established general regulator of senEV activity. Finally, we discuss candidate intervention strategies, evidence gaps, and the experimental requirements needed to define how donor-cell state, cargo composition, recipient-cell identity, treatment context and time after treatment may shape senEV function.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"5 10","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jex2.70193","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149205928","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":"Evaluating Plasma-Handling Effects on Extracellular Vesicle RNA Yield and Cargo Profiles in Fish: A Methodological Insight","authors":"Antonio Espuela-Ortiz,&nbsp;Estrella Antón-González,&nbsp;Louis Bonnefous,&nbsp;M. Virginia Martín,&nbsp;Salvador Jeréz,&nbsp;Deiene Rodríguez-Barreto","doi":"10.1002/jex2.70175","DOIUrl":"https://doi.org/10.1002/jex2.70175","url":null,"abstract":"<p>Extracellular vesicle (EV)-derived RNA (EV-RNA) is emerging as a valuable biomarker source in aquatic species. However, the composition and stability of long RNA species, particularly messenger RNA (mRNAs) and long non-coding RNAs (lncRNAs), remain largely unexplored in teleosts. Pre-analytical factors such as input plasma volume and storage conditions may influence RNA recovery, especially in low-input samples like fish plasma. Here, we evaluated the effects of input sample volume and freezing storage on EV-RNA yield and integrity in gilthead sea bream (<i>Sparus aurata)</i> plasma using the exoRNeasy commercial kit. Both Maxi (∼2 mL) and Midi (∼1 mL) kit formats produced comparable RNA recovery, indicating flexibility in plasma volume requirements. Freezing did not alter the overall RNA biotype composition or the identity of the dominant transcripts but resulted in a higher proportion of shorter and incomplete isoforms, suggesting selective susceptibility to degradation of long RNAs during freezing storage.</p><p>Using Oxford Nanopore Technologies long-read sequencing, we generated the first long RNA-resolved EV transcriptome for this species. EV cargo was dominated by ribosomal and metabolic mRNAs, consistent with conserved vertebrate EV signatures, and 302 distinct lncRNAs were identified, two of which accounted for nearly 90% of lncRNA reads. Predicted interactions between abundant lncRNAs, EV mRNAs, and their encoded ribonucleoproteins suggest coordinated packaging of RNA–protein modules.</p><p>Overall, this study validates exoRNeasy for fish plasma and provides the first comprehensive long-RNA EV landscape in a teleost, providing a valuable framework for future molecular and functional studies in non-model fish species.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"5 10","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jex2.70175","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149205927","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":"Natural Killer Cell-Derived Extracellular Vesicle Preparations Demonstrate Potent Antitumor Activity Against Human Glioblastoma In Vitro and In Vivo","authors":"Huy Phuoc Quang Nguyen,&nbsp;Meesun Yoon,&nbsp;Shin Jung,&nbsp;Duck Cho,&nbsp;Byong Seung Cho,&nbsp;Tung Nguyen Thanh Uong,&nbsp;Jae-Uk Jeong,&nbsp;Yong-Hyub Kim,&nbsp;Nhat Phuoc Nguong Minh Nguyen,&nbsp;Tien Luyen Vu","doi":"10.1002/jex2.70181","DOIUrl":"https://doi.org/10.1002/jex2.70181","url":null,"abstract":"<p>Extracellular vesicles (EVs) derived from activated natural killer (NK) cells represent a promising cell-free immunotherapy for cancer. However, the use of primary expanded human NK cell-derived EVs (NK-EVs) for intractable brain tumours is underexplored. Here, we evaluated common EV isolation methods including precipitation for bulk EVs and size exclusion chromatography (SEC) to obtain both NK-EVs and proteins. Precipitated NK-EVs demonstrated potent dose-dependent cytotoxicity against multiple glioblastoma (GBM) cell lines, including those resistant to conventional NK cell therapy. They suppressed tumour growth in subcutaneous GBM xenograft models and, following intravenous administration, significantly inhibited orthotopic brain tumour progression and prolonged survival. SEC-NK-EVs expressed high levels of activating receptors (NKG2D, DNAM-1, NKp30) and effector proteins (perforin, granzyme B) with lower inhibitory receptors (TIGIT, TIM-3, CD96 and LAG3) compared to parental cells. Importantly, both SEC-NK-EVs and proteins exhibited antitumor activity, revealing complementary therapeutic mechanisms within the NK cell secretome. Collectively, these findings establish NK-EVs as an effective cell-free immunotherapy strategy for GBM that has the potential to evade key limitations of adoptive NK cell therapy, including the immunosuppressive tumour microenvironment.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"5 10","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jex2.70181","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029105","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":"A Beginner's Guide to Study the Role of Extracellular Vesicles in Coagulation","authors":"Rienk Nieuwland,&nbsp;Jillian W. P. Bracht,&nbsp;Joost C. M. Meijers,&nbsp;Johannes Thaler","doi":"10.1002/jex2.70190","DOIUrl":"https://doi.org/10.1002/jex2.70190","url":null,"abstract":"<p>This guide provides an overview of information that is needed to understand and study the coagulant functions of extracellular vesicles (EVs) in human body fluids. Although EV research has expanded rapidly, the physiological functions of EVs remain incompletely understood, and coagulation is one of the first biological functions that was attributed to EVs. Since coagulation is a complex balance between coagulation promoting and inhibiting pathways, for clarity and to reduce complexity we focus exclusively on how EVs contribute to coagulation-promoting pathways in physiological conditions. We explain what coagulation is, and how coagulation contributes to haemostasis and host defence, followed by an overview of historical evidence showing that extracellular vesicles initiate and promote coagulation. In addition, we explain how extracellular vesicles provide a coagulation-promoting surface, and expand the classical “envelope model”. Finally, we summarize how the procoagulant activities of EVs can be measured, and provide guidance to improve the reproducibility of such measurements.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"5 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jex2.70190","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148994485","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":"Nerve Growth Factor Treatment and the Corneal Epithelium: Extracellular Vesicle-Mediated Signaling","authors":"Levi N. Kanu,&nbsp;Amit Chatterjee,&nbsp;Mohamed Y. Mahmoud,&nbsp;Vincent Yeung,&nbsp;Sushma V. Mudigunda,&nbsp;Amy E. Ross,&nbsp;Brenna Hefley,&nbsp;Dimitrios C. Karamichos,&nbsp;Joseph B. Ciolino","doi":"10.1002/jex2.70192","DOIUrl":"https://doi.org/10.1002/jex2.70192","url":null,"abstract":"<p>Recombinant human nerve growth factor (NGF) is used to treat patients with impaired corneal wound healing. NGF exerts its effects through complex signaling processes initiated by the binding of one of two cell membrane receptors—TrkA and p75NTR. While the intracellular signaling pathways have been studied extensively, how NGF mediates intercellular signaling to coordinate wound healing is less understood. Here, we demonstrate that extracellular vesicles (EVs) produced by the corneal epithelium in response to exogenous NGF negatively affect the viability, proliferation, and migration of corneal epithelial cells. We found that EVs produced in response to NGF include an over-enrichment in miR-34a-3p, while the same miRNA is under-expressed in the cell lysate after NGF treatment. Conversely, treatment with a miR-34a-3p antagonist, miR34a-i, induces a significant upregulation of endogenous NGF, suggesting a potential feedback pathway between miR-34a-3p and NGF. Furthermore, media conditioned with EVs produced in response to miR34a-i treatment significantly enhances the proliferative response in the corneal epithelium. We identified bex3—encoding NGF receptor associated protein 1—as a potential target of miR-34a-3p in the NGF signaling pathway. These data highlight a potential intercellular negative feedback pathway induced by NGF treatment in the corneal epithelium.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"5 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jex2.70192","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148994486","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 Drive Invasive Characteristics and Matrix Remodelling in Organotypic Models of Colorectal Cancer Progression","authors":"Sonia Guarnerio,&nbsp;Laura Cole,&nbsp;Rawan Maani,&nbsp;Rob Tempest,&nbsp;Alex Mirnezami,&nbsp;Paul Hughes,&nbsp;Stuart Hunt,&nbsp;Christine Le Maitre,&nbsp;Keith Chapple,&nbsp;Nick Peake","doi":"10.1002/jex2.70187","DOIUrl":"https://doi.org/10.1002/jex2.70187","url":null,"abstract":"<p>Colorectal cancer (CRC) remains a leading cause of cancer-related mortality, with metastasis accounting for over 90% of CRC deaths. While the role of extracellular vesicles (EVs) in cancer progression is recognised, their impact on invasive behaviour and extracellular matrix (ECM) remodelling within physiologically relevant three-dimensional (3D) microenvironments remains poorly understood. This study utilised quantitative organotypic 3D models to investigate how EVs derived from primary (SW480) and metastatic (SW620) CRC cell lines influence invasion, stromal activation, and ECM remodelling.</p><p>We developed models incorporating CRC cells, fibroblasts, endothelial cells, and macrophages to mimic the tumour microenvironment (TME) and lung stroma. EVs isolated from SW480 and SW620 cells were isolated and characterized according to MISEV guidelines and introduced into the models. Treatment with metastatic SW620 EVs significantly enhanced depth and extent of CRC cell invasion compared to primary SW480 EVs or controls, and increased invasion of multicellular clusters. Immunofluorescence analysis revealed elevated expression of cadherin 2 (CADH2) and catenin delta 1 (CTNND1) in SW620 EV-treated models, indicating involvement of epithelial-mesenchymal transition (EMT).</p><p>In lung stroma models, SW620 EVs reduced matrix stiffness, implying ECM remodelling. Mass spectrometry and multivariate analysis identified distinct proteomic signatures in SW620 EV-treated models, with significant alterations in collagen type XI expression and unique mass-to-charge (m/z) peaks, indicating selective ECM remodelling. SW620 EVs also induced activation of stromal fibroblasts and endothelial cells, as evidenced by increased α-smooth muscle actin (α-SMA) and von Willebrand Factor (vWF) expression.</p><p>These findings demonstrated that metastatic CRC-derived EVs enhance invasive behaviour and remodel the ECM, creating a permissive microenvironment for metastasis. The differential effects of primary versus metastatic EVs underscore the importance of tumour stage-specific vesicle signatures in CRC progression. This study provides a robust 3D model framework to quantify EV-mediated mechanisms and identify therapeutic targets to disrupt pro-metastatic communication in CRC.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"5 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jex2.70187","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148994488","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":"Proteomic Atlas of Notochordal Cell-Derived Extracellular Vesicles Highlights EV-Specific NF-κB Modulation and Functional Implications of the Protein Corona","authors":"Josette C. van Maanen,&nbsp;Chantal Voskamp,&nbsp;Frank M. Riemers,&nbsp;Harmjan R. Vos,&nbsp;Anouk Eversdijk,&nbsp;Marije Kleinjan,&nbsp;Menno Bergmeijer,&nbsp;Martijn J. C. van Herwijnen,&nbsp;Stuart C. Howes,&nbsp;Frances C. Bach,&nbsp;Tim J. M. Welting,&nbsp;Christine L. Le Maitre,&nbsp;Guus G. H. van den Akker,&nbsp;Marca H. M. Wauben,&nbsp;Mariana A. Tryfonidou","doi":"10.1002/jex2.70186","DOIUrl":"10.1002/jex2.70186","url":null,"abstract":"<p>The notochord is a central signalling hub during embryonic development. After regression of the notochord, notochordal cells (NCs) reside within the developing intervertebral disc. The NC-secretome, including matrix, proteins and extracellular vesicles (NC-EVs), promotes regeneration of degenerate intervertebral discs and cartilage. This study aims to unravel the NC-EV-associated proteome and modulatory role in regenerative processes. NC-EVs were isolated from conditioned medium from porcine NC-rich tissue using differential centrifugation, size exclusion chromatography and density gradient centrifugation. Proteomic analysis of NC-EVs was performed using LC-MS/MS and identified 4042 unique proteins, including EV-associated markers, matrisome proteins and proteins associated with critical nodes in canonical signalling pathways. To test NC-EV bioactivity, functional analysis was performed using SBE, TCF/LEF and NF-κB luciferase reporters. NC-EVs activated SMAD3 and inhibited IL-1β-mediated NF-κB signalling. NC-EV depleted controls showed similar effects, indicating that co-isolated proteins played a major role in modulating signalling. Therefore, NC-EVs were further purified and the GAG-rich biomolecular corona was modified with hyaluronidase. Post-hyaluronidase treatment, SMAD3 activation was enhanced only in methodological controls, while inhibition of IL-1β-mediated NF-κB signalling was NC-EV specific. This study is the first to reveal the NC-EV proteome and illustrates that proteins absorbed on the NC-EVs attribute to EV-mediated functional effects.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"5 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13572908/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148972680","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":"When EV Dose Is Not What It Seems: Quantitative Mismatch Between Particle Number- and Protein-Based Dosing","authors":"Tímea Böröczky,&nbsp;Mária Harmati,&nbsp;Edina Gyukity-Sebestyén,&nbsp;Tamás F. Polgár,&nbsp;Csenge Feinek,&nbsp;Emma Balog,&nbsp;Antal Martinecz,&nbsp;Krisztina Buzás,&nbsp;Gabriella Dobra,&nbsp;Mátyás Bukva","doi":"10.1002/jex2.70188","DOIUrl":"10.1002/jex2.70188","url":null,"abstract":"<p>Extracellular vesicles (EVs) are widely studied as mediators of intercellular communication, yet their quantitative characterization remains inconsistent. In this study, we investigated how vesicle release rate, cellular proliferation, and tumour origin jointly shape EV-associated protein output. Using a panel of 19 human, murine, canine and primate cancer- and non-cancer cell lines cultured under standardized conditions, we isolated small extracellular vesicle-enriched fractions and quantified particle number, EV-associated protein content, cell number and proliferation rate and integrated these parameters into three complementary, readily computable metrics: protein content per particle (PP; pg/particle), Vesicle Release Characteristics (VRC; particles/cell/24 h), and Protein Release Characteristics (PRC; pg/cell/24 h). Cancer cells showed significantly higher estimated EV release per cell than non-cancer cells (∼3.6-fold higher VRC), while their EV-enriched isolates exhibited a substantially lower protein-to-particle ratio (∼4.3-fold lower PP). Lower PP was independently associated with both cancer origin and proliferation rate and was not explained by differences in vesicle size. Despite the elevated vesicle output, cancer-derived cells exported less total vesicular protein per cell and time unit (∼2.1-fold lower PRC), and the relationship between vesicle output and total protein output itself differed between non-cancer and cancer cells. These findings demonstrate that particle number and protein content describe distinct and non-equivalent aspects of EV output. We therefore recommend integrated, multidimensional reporting (VRC, PRC, and the protein/particle descriptor PP — or vesicles per pg protein) to enable biologically meaningful comparison and dosing of EV preparations.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"5 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13572909/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148972663","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":"Comparative Assessment of Methods for Isolation and Imaging of Extracellular Vesicles","authors":"Edward Carson,&nbsp;Yue Xu,&nbsp;Muthulekha Swamydas,&nbsp;Grace Duginski,&nbsp;Viviane Luangphakdy,&nbsp;Hannah Simmons,&nbsp;Vijay Krishna,&nbsp;Ronald Midura,&nbsp;George Muschler","doi":"10.1002/jex2.70184","DOIUrl":"10.1002/jex2.70184","url":null,"abstract":"<p>Extracellular vesicles (EVs) from defined cell sources are emerging as potential vehicles with therapeutic efficacy. The EV and non-EV secretome of individual cell populations may also be used as a measure of cell identity or state. EV attributes and composition may therefore be useful in defining the “fit-for-purpose” quality of cell populations for drug testing, biological models, and cell therapy products. As such, methods for cost-effective isolation and rigorous characterization of EVs are needed. This work aims to evaluate current methods and establish effective and potentially improved techniques to address these needs.</p><p>First, ultracentrifugation, ultrafiltration, and precipitation methods were evaluated as means for EV isolation from culture-expanded human mesenchymal stromal cell (hMSC) populations. Second, traditional formvar and updated lacey carbon transmission electron microscopy (TEM) grid preparations were compared. Third, electron energy loss spectroscopy (EELS) was evaluated for EV elemental content characterization. Fourth, the efficacy of dynamic light scattering (DLS) was evaluated as a tool for characterizing variation in EV size distribution between hMSC populations. Finally, DLS measurements were compared to direct TEM size measurements using EV populations isolated from 28 culture-expanded hMSC populations derived from 5 human donors.</p><p>Ultracentrifugation was most effective in providing higher EV purity and yield per visual TEM analysis. Lacey carbon TEM grids provided the most effective imaging for visual characterization of EV morphology and enabled durable archiving of samples for discontinuous assessment. EELS identified phosphorus in the lipid bilayer but was ineffective at identifying sulfur (protein) and nitrogen (protein, RNA, DNA) contents of EVs. DLS was generally consistent in characterizing EV population size distributions, but discrepancies and limitations were identified based on direct comparative TEM observation.</p><p>This study demonstrated that ultracentrifugation, DLS size characterization, and confirmation with lacey carbon TEM grid preparation provided high quality samples and effective assessment of EV size distribution and morphology.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"5 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13572904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148972690","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":"Scalable and Controlled Production of Microalgae-derived Extracellular Vesicles Using a Differential Tangential Flow Filtration Protocol","authors":"Angela Paterna,&nbsp;Estella Rao,&nbsp;Paola Gargano,&nbsp;Sabrina Picciotto,&nbsp;Giorgia Adamo,&nbsp;Samuele Raccosta,&nbsp;Antonella Bongiovanni,&nbsp;Mauro Manno","doi":"10.1002/jex2.70185","DOIUrl":"https://doi.org/10.1002/jex2.70185","url":null,"abstract":"<p>The transition of extracellular vesicle (EV) production from laboratory to industrial scale presents major challenges in terms of standardization, scalability, and product consistency. Here, we present a scalable manufacturing strategy for nanoalgosomes, EVs derived from the microalga <i>Tetraselmis chuii</i>. The process integrates upstream cultivation under controlled conditions with downstream isolation and purification via continuous tangential flow filtration (TFF). Critical TFF parameters—cross-flow velocity, shear rate, permeate flux, and transmembrane pressure—were investigated to evaluatetheir impact on process behaviour, extracellular vesicle recovery, and functional integrity. Following the MISEV2018 guidelines established in our previous baseline characterizations, the isolated nanoalgosomes were verified by a quality control, including biochemical and biophysical characterization, confirming the robustness of the platform. Overall, this work provides a practical processing framework for the scientific community dealing with large-volume EV bioprocessing, offering an informative baseline for the scalable production of microalgae-derived extracellular vesicles.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"5 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jex2.70185","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148942894","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}