Journal of Extracellular Vesicles最新文献

{"title":"Correction to “Stress-Induced Rab11a-Exosomes Induce Amphiregulin-Mediated Cetuximab Resistance in Colorectal Cancer”","authors":"","doi":"10.1002/jev2.70081","DOIUrl":"https://doi.org/10.1002/jev2.70081","url":null,"abstract":"<p>J.D. Mason, E. Marks, S.J. Fan, K. McCormick, C. Wilson, A.L. Harris, F.C. Hamdy, C. Cunningham, and D.C.I. Goberdhan, “Stress-Induced Rab11a-Exosomes Induce Amphiregulin-Mediated Cetuximab Resistance in Colorectal Cancer,” <i>Journal of Extracellular Vesicles</i> 13, no. 6 (2024): e12465, https://doi.org/10.1002/jev2.12465.</p><p>In the original article, the data in Figure 1b, which had previously been published in Fan et al. 2020 <i>EMBO J</i> 39(16), e103009, was inadvertently included, in addition to citing this article. This panel has now been removed. Published below is the correct version of Figure 1 with its modified legend and a slightly modified version of the first results section text, in which this figure and the associated Figure S2 are cross-referenced.</p><p>In the original article, the data in Figure S2b, which was associated with Figure 1b and had previously been published in Fan et al. 2020 <i>EMBO J</i> 39(16), e103009, was inadvertently included. This has now been removed, and the corrected version of this figure is included in the new Supplementary Information file.</p><p>In the original article, the wrong tubulin blot was mistakenly included in Figure S3g. This has now been corrected and included in the new Supplementary Information file.</p><p>These mistakes do not affect the significance of the findings or the conclusions in this article. We apologise for these errors.</p><p>In HCT116 cells, downregulation of the mTORC1 signalling pathway in response to glutamine depletion leads to a switch to increased secretion of Rab11a-exosomes carrying membrane-bound AREG and Rab11a. It does not, however, affect the levels of other exosome and EV proteins in sEV preparations, except for late endosomal marker CD63, which is reduced under stress conditions (Fan et al., 2020; Marie et al., 2023). Experiments using immuno-affinity separation of sEVs and selective inhibition of Rab11a-exosome secretion suggest that unlike AREG, scaffolding protein Cav-1, which is also elevated in Rab11a-exosome-enriched sEV preparations, is associated with alternative stress-induced vesicles that co-separate with Rab11a-exosomes (Fan et al., 2020; Marie et al., 2023). The decrease in sEV-associated CD63 is partially caused by a stress-induced reduction in trafficking and exosome secretion through the late endosomal pathway (Fan et al., 2020).</p><p>Hypoxia, a common microenvironmental stress in fast-growing tumours, previously shown to alter sEV cargos in glioblastoma cells (Kurcharzewska et al., 2013), also inhibited mTORC1 in HCT116 cells, as determined by reduced phospho-S6 and phosphorylated forms of 4E-BP1 in western blots of cell lysates (Figure S2b). While only the exosome and sEV proteins CD81 (decreased) and AREG (increased) were significantly changed in cell lysates (Figure S2b), hypoxia induced a significant increase in Rab11a, Cav-1 and AREG in sEV preparations, consistent with elevated Rab11a-exosome secretion (Figure 1b). In contrast to g","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 5","pages":""},"PeriodicalIF":15.5,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70081","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143897225","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":"Nano-Flow Cytometry-Guided Discrimination and Separation of Human Cytomegalovirus Virions and Extracellular Vesicles","authors":"Vladimir Bokun,&nbsp;Blair L. Strang,&nbsp;Paschalia Pantazi,&nbsp;Yan Liu,&nbsp;Beth Holder","doi":"10.1002/jev2.70060","DOIUrl":"https://doi.org/10.1002/jev2.70060","url":null,"abstract":"<p>Accurate quantification and physical separation of viral particles and extracellular vesicles (EVs) produced by virus-infected cells presents a significant challenge due to their overlapping physical and biochemical properties. Most analytical methods provide information on a particle mixture as a whole, without distinguishing viral particles from EVs. By utilising nano-flow cytometry (nFC), a specialised form of flow cytometry adapted for the investigation of nanoparticles, we developed a simple, nucleic acid staining-based method for discrimination and simultaneous quantification of the human cytomegalovirus (HCMV) virions, dense bodies and EVs, within extracellular particle mixtures produced by HCMV-infected cells. We show that nucleic acid staining allows for discrimination of the individual particle types based on their distinct fluorescence/side scatter profiles, assessed at single-particle level by nFC. Following this, we optimised a method for physical separation of EVs from viral particles, based on high-speed centrifugation through density cushions, using nFC as a tool to evaluate the purity of the isolated EVs. The methods introduced here have the capacity to circumvent common difficulties associated with the co-investigation of EVs and viruses.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 5","pages":""},"PeriodicalIF":15.5,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70060","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143896968","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":"Erythrocyte Extracellular Vesicles Amalgamate into the Hair and Skin to Maintain Homeostasis","authors":"Zeyuan Cao,&nbsp;Peiyi Li,&nbsp;Manjin Zhang,&nbsp;Simin Cai,&nbsp;Na Li,&nbsp;Mingtao Luo,&nbsp;Yinghui Li,&nbsp;Haolin Wu,&nbsp;Xueli Mao,&nbsp;Ruibao Ren,&nbsp;Hongju Xie,&nbsp;Songtao Shi","doi":"10.1002/jev2.70080","DOIUrl":"https://doi.org/10.1002/jev2.70080","url":null,"abstract":"<p>Erythrocytes are a major cell type in the circulation, numbering between 20 and 30 trillion. The function of erythrocytes is to bring oxygen to the tissues and release carbon dioxide to the lungs. Anaemic patients, who have low levels of erythrocytes, show significant symptoms affecting the hair and skin; however, the detailed relationship between erythrocytes and the integumentary system is not fully understood. Here, we show that erythrocyte extracellular vesicle (EV) can transfer haemoglobin, ABO antigens and keratin into the hair and promote hair regeneration through miR-20a-5p- and miR-22-3p-mediated upregulation of Wnt/β-catenin signalling in dermal papilla cells. Moreover, we show that local injection of autologous erythrocyte EVs ameliorates hair growth in androgenic alopecia (AGA) patients. Interestingly, we found that erythrocyte EVs exit the body from the hair/skin and their membranes contribute to the formation of the outer barrier of the skin. In summary, we identify a previously unknown role of erythrocytes in amalgamating into hair structures and reveal a new therapeutic approach using erythrocyte EVs to promote hair regeneration in AGA patients.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 5","pages":""},"PeriodicalIF":15.5,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70080","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143897167","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":"Beta-Lactam Antibiotics Promote Extracellular Vesicle Production of Staphylococcus aureus Through ROS-Mediated Lipid Metabolic Reprogramming","authors":"Xiaonan Huang,&nbsp;Zhen Hu,&nbsp;Weilong Shang,&nbsp;Juan Chen,&nbsp;Qiwen Hu,&nbsp;Yumin Zhou,&nbsp;Ruolan Ding,&nbsp;Jing Yin,&nbsp;Mengyang Li,&nbsp;He Liu,&nbsp;Jianxiong Dou,&nbsp;Huagang Peng,&nbsp;Yifan Rao,&nbsp;Lu Liu,&nbsp;Yuting Wang,&nbsp;Li Tan,&nbsp;Yuhua Yang,&nbsp;Jianghong Wu,&nbsp;Chuan Xiao,&nbsp;Yi Yang,&nbsp;Xiancai Rao","doi":"10.1002/jev2.70077","DOIUrl":"https://doi.org/10.1002/jev2.70077","url":null,"abstract":"<p>Bacterial extracellular vesicles (EVs) are natural reservoirs of biological active substances. They exhibit promising application in developing bioproducts such as vaccine, drug-delivery system and anticancer agent. However, the low yield of naturally secreted EVs during bacterial growth is a bottleneck factor that restricts EV applications. In this study, we showed that sub-minimum inhibitory concentration (MIC) of β-lactams boosted EV production in various <i>Staphylococcus aureus</i> strains. The expression of penicillin-binding protein (PBP) genes increased after β-lactam treatment, and the inactivation of alternative PBPs promoted EV secretion of <i>S. aureus</i>. We also demonstrated that sub-MIC β-lactams promoted EV production via a reactive oxygen species (ROS)-dependent pathway. Deletion of redundant <i>pbp</i> genes enhanced oxacillin (OXA)-stimulated ROS levels. Transcriptomic and lipidomic analyses revealed that OXA-induced ROS triggered lipid metabolic reprogramming in <i>S. aureus</i>. Particularly, ROS promoted lipid peroxidation (LPO) and increased the biosynthesis of phosphatidic acid (PA) and lipoteichoic acid (LTA) that contributed to EV generation. Furthermore, OXA treatment altered the diversity of EV-loaded proteins. OXA-treated ^∆<i>^agr</i>^/OXAEVs induced stronger Dengue EDIII-specific antibodies in BALB/c mice than did ^∆<i>^agr</i>EVs. Overall, this study provided mechanic insights into β-lactam-promoted EV production in <i>S. aureus</i>, and highlighted the potential strategies to prepare EVs for various applications.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 5","pages":""},"PeriodicalIF":15.5,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70077","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143897128","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":"1,4-Dioxane Induces Epithelial-Mesenchymal Transition and Carcinogenesis in an Nrf2-Dependent Manner","authors":"Ziwei Wang,&nbsp;Chitra Thakur,&nbsp;Zhuoyue Bi,&nbsp;Yiran Qiu,&nbsp;Wenxuan Zhang,&nbsp;Haoyan Ji,&nbsp;Arjun K. Venkatesan,&nbsp;Sashank Cherukuri,&nbsp;Ke Jian Liu,&nbsp;John D. Haley,&nbsp;Xinwei Mao,&nbsp;Jaymie Meliker,&nbsp;Fei Chen","doi":"10.1002/jev2.70072","DOIUrl":"https://doi.org/10.1002/jev2.70072","url":null,"abstract":"<p>The carcinogenic potential of the environmental pollutant 1,4-dioxane (1,4-D) in humans is not yet fully understood or recognised. In this study, we provide evidence that 1,4-D acts as a carcinogen in human epithelial cells. Using the human bronchial epithelial cell line BEAS-2B, with or without CRISPR-Cas9-mediated Nrf2 knockout, we demonstrate that continuous exposure to environmentally relevant concentrations of 1.25–20 ppm 1,4-D over 2 months induces malignant transformation in an Nrf2-dependent manner. Transformed cells exhibit enhanced anchorage-independent growth in soft agar, increased migration and invasion, and tumorigenic potential in a xenograft mouse model. Integrated RNA sequencing and proteomics analyses reveal that 1,4-D robustly activates Nrf2 signalling, driving extracellular vesicle (EV) biogenesis and cargo loading with syndecan 4 (SDC4) and other proteins, including COL12A1, CAPG and NNMT, which are associated with epithelial-mesenchymal transition (EMT) and cancer metastasis. Nrf2 knockout reduces SDC4 expression and its incorporation into EVs, leading to decreased EV uptake by recipient cells. Unlike EVs from 1,4-D-transformed WT cells, which enhance the proliferation, migration and invasion of recipient cells, EVs from 1,4-D-transformed Nrf2 KO cells exhibit a diminished capacity to promote these EMT properties. Furthermore, we demonstrate that the Nrf2 target gene <i>SDC4</i>, induced by 1,4-D and enriched in EVs, plays a critical role in EV uptake by recipient cells, thereby facilitating EMT propagation. Collectively, our findings suggest that 1,4-D is a human carcinogen, with its carcinogenicity largely dependent on Nrf2 activation, which orchestrates the biogenesis of EVs with EMT-promoting functions.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 5","pages":""},"PeriodicalIF":15.5,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70072","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893015","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":"Plasma Extracellular Vesicle-Derived miR-296-5p is a Maturation-Dependent Rejuvenation Factor that Downregulates Inflammation and Improves Survival after Sepsis","authors":"Lun Cai,&nbsp;Parmita Kar,&nbsp;Yutao Liu,&nbsp;Xiaogang Chu,&nbsp;Ashok Sharma,&nbsp;Tae Jin Lee,&nbsp;Ali Arbab,&nbsp;Raghavan Pillai Raju","doi":"10.1002/jev2.70065","DOIUrl":"https://doi.org/10.1002/jev2.70065","url":null,"abstract":"<p>There is a progressive decline in physiological function with age, and aging is associated with increased susceptibility to injury and infection. However, several reports have indicated that the agility of youth is characterized by transferable rejuvenating molecular factors, as was observed previously in heterochronic parabiosis experiments. These experiments demonstrated a rejuvenating effect of young blood in old animals. There have been several efforts to characterize these youthful or maturation-associated factors in the young blood. In this report, we demonstrate the resilience of young mice, at or before puberty, to polymicrobial sepsis and show an age-dependent effect of small extracellular vesicles (EVs) from plasma on the outcome following sepsis. The EVs from the young mice were cytoprotective, anti-inflammatory, and reduced cellular senescence markers. MicroRNA sequencing of the EVs showed an age-associated signature and identified miR-296-5p and miR-541-5p to progressively reduce their levels in the blood plasma with increasing age. We further show that the levels of these miRNAs decline with age in multiple organs. The miRNAs miR-296-5p and miR-541-5p showed a reparatory effect in an in vitro wound healing model and the miR-296-5p, when given intraperitoneally, reduced mortality in the mouse model of sepsis. In summary, our studies demonstrate that EVs from very young mice have a reparative effect on sepsis, and the reparative factors are likely maturation-dependent. Our observation that miR-296-5p and miR-541-5p are plasma EV constituents that significantly reduce with age and can reduce inflammation suggests a therapeutic potential for these miRNAs in inflammation and age-associated diseases.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 4","pages":""},"PeriodicalIF":15.5,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70065","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143875669","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 \"DetectEV: a Functional Enzymatic Assay to Assess Integrity and Bioactivity of Extracellular Vesicles\"","authors":"","doi":"10.1002/jev2.70075","DOIUrl":"https://doi.org/10.1002/jev2.70075","url":null,"abstract":"<p>G. Adamo, S. Picciotto, P. Gargano, et al, “DetectEV: A Functional Enzymatic Assay to Assess Integrity and Bioactivity of Extracellular Vesicles,” <i>Journal of Extracellular Vesicles</i>, 14 (2025): e70030. https://doi.org/10.1002/jev2.70030</p><p>In the originally published article, the term ‘mol’ (along with its derivatives ‘nmol’ and ‘µmol’) was mistakenly used instead of ‘M’ (molarity). This issue affects only the notation and does not impact the data, observations, or conclusions of the article. The correct notation is ‘M’ (along with its derivatives ‘nM’ and ‘µM’), as the reference is to concentrations rather than absolute quantities.</p><p>We apologise for this error.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 4","pages":""},"PeriodicalIF":15.5,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70075","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143840791","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":"Small Extracellular Vesicle-Derived Nicotinamide Phosphoribosyltransferase (NAMPT) Induces Acyl-Coenzyme A Synthetase SLC27A4-Mediated Glycolysis to Promote Hepatocellular Carcinoma","authors":"Cherlie Lot Sum Yeung,&nbsp;Tung Him Ng,&nbsp;Charlotte Jiaqi Lai,&nbsp;Tingmao Xue,&nbsp;Xiaowen Mao,&nbsp;Sze Keong Tey,&nbsp;Regina Cheuk Lam Lo,&nbsp;Chun-Fung Sin,&nbsp;Kwan Ming Ng,&nbsp;Danny Ka Ho Wong,&nbsp;Lung-Yi Mak,&nbsp;Man-Fung Yuen,&nbsp;Irene Oi-Lin Ng,&nbsp;Peihua Cao,&nbsp;Yi Gao,&nbsp;Jing Ping Yun,&nbsp;Judy Wai Ping Yam","doi":"10.1002/jev2.70071","DOIUrl":"https://doi.org/10.1002/jev2.70071","url":null,"abstract":"<p>Tumour-derived small extracellular vesicles (sEV) are critical mediators within the tumour microenvironment (TME) and are known to regulate various metabolic pathways. In metastatic hepatocellular carcinoma (HCC), mass spectrometry protein analysis of HCC-derived sEV (HCC-sEV) identified an upregulation of nicotinamide phosphoribosyltransferase (NAMPT), a key enzyme in maintaining cellular nicotinamide adenine dinucleotide (NAD+) levels. Our study demonstrates that sEV-NAMPT enhances glycolysis, tumorigenesis, and metastasis in HCC. Specifically, sEV-NAMPT activates the NF-κB transcription factor through toll-like receptor 4 (TLR4), leading to elevated SLC27A4 expression. SLC27A4 functions primarily as a long-chain fatty acid transporter and acyl-CoA synthetase. Lipidomic and metabolomic analyses revealed a positive correlation between SLC27A4 and intracellular levels of triacylglycerol (TG) and dihydroxyacetone phosphate (DHAP). Increased TG levels enhance lipolysis via hepatic lipase and facilitate the conversion of glycerol-3-P to DHAP, an intermediate that bridges lipid metabolism and glycolysis. This study uncovers a novel regulatory axis involving sEV-NAMPT and SLC27A4 in glycolysis, independent of traditional fatty acid metabolism pathways. Clinically, targeting sEV-NAMPT with the inhibitor FK866 significantly inhibited tumour growth in various HCC in vivo models, highlighting the potential of sEV-NAMPT as both a biomarker and therapeutic target in HCC.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 4","pages":""},"PeriodicalIF":15.5,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70071","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143836192","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":"Microbead Encapsulation Strategy for Efficient Production of Extracellular Vesicles Derived From Human Mesenchymal Stem Cells","authors":"Yunxia Hu,&nbsp;Lijuan Zheng,&nbsp;Zheng Zheng,&nbsp;Mali Fu,&nbsp;Haiying Peng,&nbsp;Shaohua Ma","doi":"10.1002/jev2.70053","DOIUrl":"https://doi.org/10.1002/jev2.70053","url":null,"abstract":"<p>Human mesenchymal stem cell-derived extracellular vesicles (hMSC-EVs) have shown great potential in tissue repair and regeneration. However, their scalable production and functional quality are still limited by current expansion technologies. In this study, we propose a production technology for hMSC-EVs based on three-dimensional (3D) microbead culture, which enhances the secretory behaviour of hMSC. Fixed number of MSCs were encapsulated in Matrigel at appropriate densities and printed into 3D microbeads by the custom automated microfluidic bead-jet printing technique. Compared with 2D culture group, EVs derived from 3D hMSC microbead had smaller size and increased yield by 20-fold, and the actin depolymerisation of the cell may be an important mechanism for enhancing EV secretion. Further analysis confirmed that the EVs derived from 3D hMSC microbead exhibited enhanced angiogenic and proliferative capabilities, which promoted the viability and tube-forming capacity of human umbilical vein endothelial cells (HUVEC). In conclusion, this automated microfluidic microbead encapsulation technology increased the yield and therapeutic effect of hMSC-EVs and provides a platform for scalable EV production of regenerative therapies.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 4","pages":""},"PeriodicalIF":15.5,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70053","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143840793","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":"Dendritic Cell Derived-Extracellular Vesicles Engineered to Express Interleukin-12 and Anti-CTLA-4 on Their Surface for Combinational Cancer Immunotherapy","authors":"Jiangbin Chen,&nbsp;Qi Tan,&nbsp;Zimo Yang,&nbsp;Wenjuan Chen,&nbsp;E. Zhou,&nbsp;Minglei Li,&nbsp;Jingjing Deng,&nbsp;Yali Wu,&nbsp;Jiatong Liu,&nbsp;Juanjuan Xu,&nbsp;Mengfei Guo,&nbsp;Yang Jin","doi":"10.1002/jev2.70068","DOIUrl":"https://doi.org/10.1002/jev2.70068","url":null,"abstract":"<p>Dendritic cell (DC)-derived extracellular vesicles (DEVs) are promising candidates for cancer vaccines, but their therapeutic effects still need further optimization. In this study, we utilized neoantigens, lipopolysaccharide and IFN-γ to induce the maturation of DCs, and then isolated DEVs derived from these mature DCs. We showed that the immune checkpoint inhibitor (anti-CTLA-4 antibody, aCTLA-4) can improve the immunostimulatory function of DEVs by directly activating T cells through immune checkpoint signal blockade. The cytokine interleukin-12 (IL-12), as one of the third signals for T cell activation, can also enhance the capability of DEVs to activate T cells directly. Based on these findings, we designed the engineered DEVs conjugated with IL-12 and aCTLA-4 (DEV@IL-12-aCTLA-4) to improve the therapeutic potential of DEVs by providing sufficient immune regulatory signals. Moreover, the carrier property of DEVs also contributes to the delivery of IL-12 and aCTLA-4 to lymph nodes. This indicates that the conjugation of DEVs with IL-12 and aCTLA-4 constitutes a complementary approach, where IL-12 and aCTLA-4 help to enhance the T cell activation effect of DEVs, and DEVs facilitate the delivery of IL-12 and aCTLA-4. Our results showed that DEV@IL-12-aCTLA-4 can enhance the Th1 immune response and reverse exhausted CD8⁺ T cells in the tumour microenvironment, effectively inducing robust T cell immune responses and inhibiting tumour growth in tumour-bearing mice. Overall, this study expands the theoretical foundation of DEVs and provides a universal strategy for optimizing cancer combination immunotherapy by reprogramming DEVs.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 4","pages":""},"PeriodicalIF":15.5,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70068","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143840796","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}