Journal of Extracellular Vesicles最新文献

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Comparative Assessment of Whole Organ Tissue Processing Methods for the Isolation of Extracellular Vesicles From Intact Organs 从完整器官中分离细胞外囊泡的全器官组织处理方法的比较评价
IF 14.5 1区 医学
Journal of Extracellular Vesicles Pub Date : 2025-09-03 DOI: 10.1002/jev2.70127
Mohammed Tayab Hussain, Shani Austin-Williams, Joel McCay, Hedayatullah Hayat, Thomas D. Wright, Marilena Christoforou, Ella Ykema, Mauro Perretti, Dianne Cooper, Andreas Margraf
{"title":"Comparative Assessment of Whole Organ Tissue Processing Methods for the Isolation of Extracellular Vesicles From Intact Organs","authors":"Mohammed Tayab Hussain,&nbsp;Shani Austin-Williams,&nbsp;Joel McCay,&nbsp;Hedayatullah Hayat,&nbsp;Thomas D. Wright,&nbsp;Marilena Christoforou,&nbsp;Ella Ykema,&nbsp;Mauro Perretti,&nbsp;Dianne Cooper,&nbsp;Andreas Margraf","doi":"10.1002/jev2.70127","DOIUrl":"10.1002/jev2.70127","url":null,"abstract":"<p>Extracellular vesicles (EVs) are small anuclear cellular membrane encapsulated fragments of importance for cellular interaction and transfer of information. These small vesicles, diverse in size and functionality, can be obtained from cells, tissues and bodily fluids. A complicated step for obtaining EVs from whole organs is understanding the optimal methodology for organ processing. In this study, we have examined two different techniques: one enzymatic and one novel non-enzymatic automated tissue dissociation (ATD) machine. Animals were perfused, organs extracted, and techniques comparatively applied. We have used these techniques for organ-based dissociation followed by EV isolation from the dissociated tissues (heart, kidney, lung). While both approaches allow isolation of intact EVs there are distinct differences in overall cell and particle yields. Our study highlights tissue specific inter-organ variability and differential impact of dissociation strategies on organ-based EV profiles, as well as cellular characteristics. Our findings indicate that EV yields and characteristics varies between enzymatic and ATD techniques as well as between organs with highest EV yield obtained from kidneys following enzymatic dissociation. Our findings can be rapidly transferred to other setups or developed to enable enumeration and characterization of EVs obtained from whole organs in physiological and pathological settings.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 9","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://isevjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70127","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144935090","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}
引用次数: 0
Bioactive Silk Fibroin Hydrogel Harnesses BMSCs-EVs to Modulate Inflammatory Microenvironment in Intervertebral Disc Degeneration 生物活性丝素蛋白水凝胶利用bmscs - ev调节椎间盘退变炎症微环境
IF 14.5 1区 医学
Journal of Extracellular Vesicles Pub Date : 2025-09-03 DOI: 10.1002/jev2.70159
Qi Liu, Jiaying Luo, Huan Wang, Shaoqian Cui
{"title":"Bioactive Silk Fibroin Hydrogel Harnesses BMSCs-EVs to Modulate Inflammatory Microenvironment in Intervertebral Disc Degeneration","authors":"Qi Liu,&nbsp;Jiaying Luo,&nbsp;Huan Wang,&nbsp;Shaoqian Cui","doi":"10.1002/jev2.70159","DOIUrl":"10.1002/jev2.70159","url":null,"abstract":"<p>Intervertebral disc degeneration (IVDD) is a common age-related disorder associated with inflammation, pain and impaired mobility. In this study, we developed a therapeutic system using silk fibroin (SF) hydrogel loaded with mRNA-engineered extracellular vesicles derived from murine bone marrow mesenchymal stem cells (BMSCs-EVs) to modulate macrophage polarization and alleviate IVDD. BMSCs were isolated from 6-week-old C57BL/6 mice, and an acute IVDD model was established via 18G needle puncture of the coccygeal discs (Co7-Co10). RAW 264.7 murine macrophages were used for in vitro assays, with M1 polarization induced by LPS and IFN-γ. The SF/EVs complex was characterized by SEM, FTIR and rheology, confirming its structural suitability for EV delivery. Functionally, SF hydrogel not only served as a biocompatible carrier but also enabled sustained release of EVs, enhancing their anti-inflammatory effects. In vitro, SF/EVs inhibited M1 polarization and promoted M2 marker expression. In vivo implantation improved disc histology and reduced inflammatory macrophage infiltration. High-throughput RNA sequencing identified S100B as a key functional cargo within EVs. Lentivirus-mediated overexpression and knockdown experiments confirmed that EV-derived S100B suppresses M1 polarization and mitigates IVDD progression. In summary, SF hydrogel loaded with S100B-enriched BMSCs-EVs offers a promising strategy to reshape the inflammatory microenvironment and promote disc regeneration in IVDD.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 9","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://isevjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70159","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144935091","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}
引用次数: 0
Genotype-Specific Small EVs Released by Giardia lamblia Act as Mediators of Phenotypic Adaptation Under Metronidazole-Induced Stress 兰氏贾第鞭毛虫释放的基因型特异性小ev作为甲硝唑诱导胁迫下表型适应的介质
IF 14.5 1区 医学
Journal of Extracellular Vesicles Pub Date : 2025-09-01 DOI: 10.1002/jev2.70139
Gabriel Luna Pizarro, Jerónimo Laiolo, Nehuén Salas, Rocío G. Patolsky, Luciano Díaz Pérez, Camilo Cotelo, Constanza Feliziani, Andrea Silvana Rópolo, María Carolina Touz
{"title":"Genotype-Specific Small EVs Released by Giardia lamblia Act as Mediators of Phenotypic Adaptation Under Metronidazole-Induced Stress","authors":"Gabriel Luna Pizarro,&nbsp;Jerónimo Laiolo,&nbsp;Nehuén Salas,&nbsp;Rocío G. Patolsky,&nbsp;Luciano Díaz Pérez,&nbsp;Camilo Cotelo,&nbsp;Constanza Feliziani,&nbsp;Andrea Silvana Rópolo,&nbsp;María Carolina Touz","doi":"10.1002/jev2.70139","DOIUrl":"10.1002/jev2.70139","url":null,"abstract":"<p><i>Giardia lamblia</i>, a eukaryotic intestinal parasite, produces small extracellular vesicles (sEVs) as a conserved evolutionary mechanism. This study investigates the functional role of sEVs in modulating drug response traits among <i>G. lamblia</i> parasites. Here, we showed that sEVs derived from metronidazole (MTZ)–resistant clones modify the expression of enzymes involved in MTZ metabolism and the production of reactive oxygen species (ROS) in recipient wild type parasites. The transfer efficiency and phenotypic impact vary depending on the genetic background of the isolates, highlighting a genotype-specific mechanism. Our findings reveal that sEVs act as mediators of phenotypic adaptation in <i>G. lamblia</i>, enhancing parasite survival under drug-induced stress. This study highlights the significance of sEVs in drug-sensitive dynamics and lays the groundwork for investigating therapeutic interventions that target EV-mediated sensitivity in giardiasis.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 9","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://isevjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70139","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144923424","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}
引用次数: 0
USP5-Rich Apoptotic Extracellular Vesicles Regulate Nucleus Pulposus Cells Apoptosis and DNA Damage Repair by Preventing E2F1 Proteasomal Degradation 富含usp5的凋亡细胞外囊泡通过阻止E2F1蛋白酶体降解调节髓核细胞凋亡和DNA损伤修复
IF 14.5 1区 医学
Journal of Extracellular Vesicles Pub Date : 2025-08-20 DOI: 10.1002/jev2.70148
Pengzhi Shi, Haiyang Gao, Zhangrong Cheng, Wenbo Wu, Anran Zhang, Xianglong Chen, Wang Wu, Yukun Zhang
{"title":"USP5-Rich Apoptotic Extracellular Vesicles Regulate Nucleus Pulposus Cells Apoptosis and DNA Damage Repair by Preventing E2F1 Proteasomal Degradation","authors":"Pengzhi Shi,&nbsp;Haiyang Gao,&nbsp;Zhangrong Cheng,&nbsp;Wenbo Wu,&nbsp;Anran Zhang,&nbsp;Xianglong Chen,&nbsp;Wang Wu,&nbsp;Yukun Zhang","doi":"10.1002/jev2.70148","DOIUrl":"10.1002/jev2.70148","url":null,"abstract":"<p>Mesenchymal stem cell (MSC) transplantation is considered one of the most promising regenerative strategies for treating degenerative musculoskeletal diseases, yet its underlying therapeutic mechanisms remain incompletely understood. In this study, we demonstrate that transplanted MSCs regulate apoptosis and DNA damage repair (DDR) in senescent nucleus pulposus cells (NPCs) by releasing apoptotic extracellular vesicles (ApoEVs), thereby delaying the process of intervertebral disc degeneration (IVDD). Mechanistically, we found that NPCs in degenerated discs exhibit abnormal subcellular localization of the deubiquitinase ubiquitin specific peptidase 5 (USP5), with excessive cytoplasmic retention leading to aberrant ubiquitination and degradation of the E2F transcription factor 1 (E2F1). Following transplantation into the degenerative disc microenvironment, MSCs undergo extensive apoptosis in the short-term and release ApoEVs enriched in highly acetylated USP5. These vesicles promote nuclear translocation of USP5 in NPCs, which stabilizes E2F1 by preventing its ubiquitin-mediated degradation. This cascade reduces DNA damage and apoptosis in NPCs and enhances their functional activity. Overall, our findings reveal a previously unrecognized mechanism by which apoptotic donor MSCs exert therapeutic effects through intercellular communication, specifically by modulating recipient NPCs apoptosis and DDR pathways. This study underscores the critical role of donor cell apoptosis in the therapeutic efficacy of stem cell transplantation and provides new insights for optimizing regenerative medicine strategies.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 8","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://isevjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70148","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144869747","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}
引用次数: 0
GMP-Compliant Process for the Manufacturing of an Extracellular Vesicles-Enriched Secretome Product Derived From Cardiovascular Progenitor Cells Suitable for a Phase I Clinical Trial 适用于I期临床试验的心血管祖细胞衍生的细胞外囊泡富集分泌组产品的gmp合规生产工艺
IF 14.5 1区 医学
Journal of Extracellular Vesicles Pub Date : 2025-08-20 DOI: 10.1002/jev2.70145
Camille Humbert, Chloé Cordier, Iouri Drut, Michele Hamrick, Jacquelyn Wong, Valérie Bellamy, Justine Flaire, Kiranmayee Bakshy, Florent Dingli, Damarys Loew, Jérôme Larghero, Jean-Roch Fabreguettes, Philippe Menasché, Nisa K. Renault, Guillaume Churlaud
{"title":"GMP-Compliant Process for the Manufacturing of an Extracellular Vesicles-Enriched Secretome Product Derived From Cardiovascular Progenitor Cells Suitable for a Phase I Clinical Trial","authors":"Camille Humbert,&nbsp;Chloé Cordier,&nbsp;Iouri Drut,&nbsp;Michele Hamrick,&nbsp;Jacquelyn Wong,&nbsp;Valérie Bellamy,&nbsp;Justine Flaire,&nbsp;Kiranmayee Bakshy,&nbsp;Florent Dingli,&nbsp;Damarys Loew,&nbsp;Jérôme Larghero,&nbsp;Jean-Roch Fabreguettes,&nbsp;Philippe Menasché,&nbsp;Nisa K. Renault,&nbsp;Guillaume Churlaud","doi":"10.1002/jev2.70145","DOIUrl":"10.1002/jev2.70145","url":null,"abstract":"<p>Extracellular vesicle (EV)-enriched secretomes are emerging as a new and innovative therapeutic option in the field of regenerative medicine. The clinical use of EV-enriched secretome-based products requires manufacturing processes and quality control (QC) testing that comply with current good manufacturing practice (GMP). The goal of this work was to develop a robust and reproducible large-scale GMP-compliant process for the production of an EV-enriched secretome derived from cardiovascular progenitor cells (CPC), including the vesiculation of CPC, purification and concentration of the product; and sterilising filtration. QC strategies for in-process and release testing of an investigational medicinal product (IMP) were developed to guarantee quantity, safety, purity and identity. The IMP showed biological activity and was non-immunogenic in vitro, and showed no signs of toxicity or tumour development in vivo. The IMP was approved for use in a single-centre Phase I clinical trial by the French National Agency for Medicines and Health (<i>ANSM</i>) for the treatment of heart failure. The IMP is stored between –65°C and –85°C and can be easily diluted by the hospital pharmacy for infusion to the patient. This work represents a major advance for the use of CPC derived EV-enriched secretomes as a biological drug for cardiac clinical applications.</p><p><b>Trial Registration</b>: ClinicalTrials.gov identifier: NCT05774509</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 8","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://isevjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70145","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144869748","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}
引用次数: 0
IFN-γ-Induced CD317 Tethers Extracellular Vesicles to Mesenchymal Stromal Cells Interfering With Immune Modulation 干扰素-γ诱导的CD317将细胞外囊泡拴在间充质间质细胞上干扰免疫调节
IF 14.5 1区 医学
Journal of Extracellular Vesicles Pub Date : 2025-08-20 DOI: 10.1002/jev2.70155
Anton Selich, Luisa Weisskoeppel, Ralf Hass, Jan Hegermann, Adrian Schwarzer, Constantin von Kaisenberg, Axel Schambach, Michael Rothe
{"title":"IFN-γ-Induced CD317 Tethers Extracellular Vesicles to Mesenchymal Stromal Cells Interfering With Immune Modulation","authors":"Anton Selich,&nbsp;Luisa Weisskoeppel,&nbsp;Ralf Hass,&nbsp;Jan Hegermann,&nbsp;Adrian Schwarzer,&nbsp;Constantin von Kaisenberg,&nbsp;Axel Schambach,&nbsp;Michael Rothe","doi":"10.1002/jev2.70155","DOIUrl":"10.1002/jev2.70155","url":null,"abstract":"<p>In spite of the numerous clinical trials conducted on mesenchymal stromal cells and their extracellular vesicles (MSC-EVs) across a wide range of diseases, the field faces challenges in reaching a consensus on crucial parameters such as source, marker definition, and culture conditions, adding to heterogeneous efficiencies. Nevertheless, there is widespread acceptance of the pro-inflammatory activation of MSCs with IFN-γ and TNF-α to enhance immune modulation. Our study highlights the impact of activation duration on MSC-EV-mediated immune modulation of macrophages. Extended activation periods (24 h) revealed elevated levels of IFN-γ-induced CD317 on the MSC surface. CD317 is known to tether enveloped viral particles to the cell membrane, impeding viral diffusion and spread. We demonstrated the accumulation of EVs on the MSC cell surface following activation or lentiviral CD317 overexpression. In contrast, CD317 knockdown eliminated the enrichment of EVs on the cell surface, significantly enhancing the MSC-EV-mediated immune modulation of macrophages. Considering the pivotal role of IFN-γ in MSC immune modulation and its inevitable contact in patients, our findings propose CD317 as a potential modulator of MSC-based therapy efficacy in clinical applications.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 8","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://isevjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70155","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144869749","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}
引用次数: 0
Targeting Reticulin 4 (RTN4) Within Small Extracellular Vesicles Combats Metastasis and Reinforces Immunotherapy in Triple-Negative Breast Cancer 细胞外小泡内靶向网状蛋白4 (RTN4)对抗转移并加强三阴性乳腺癌的免疫治疗
IF 14.5 1区 医学
Journal of Extracellular Vesicles Pub Date : 2025-08-20 DOI: 10.1002/jev2.70154
Han Wang, Renhong Huang, Lei Luo, Ruo Wang, Ziling Zhou, Jin Hong, Jiayi Wu, Ou Huang, Jianrong He, Weiguo Chen, Yafen Li, Xiaosong Chen, Yang Wang, Zheng Wang, Kunwei Shen
{"title":"Targeting Reticulin 4 (RTN4) Within Small Extracellular Vesicles Combats Metastasis and Reinforces Immunotherapy in Triple-Negative Breast Cancer","authors":"Han Wang,&nbsp;Renhong Huang,&nbsp;Lei Luo,&nbsp;Ruo Wang,&nbsp;Ziling Zhou,&nbsp;Jin Hong,&nbsp;Jiayi Wu,&nbsp;Ou Huang,&nbsp;Jianrong He,&nbsp;Weiguo Chen,&nbsp;Yafen Li,&nbsp;Xiaosong Chen,&nbsp;Yang Wang,&nbsp;Zheng Wang,&nbsp;Kunwei Shen","doi":"10.1002/jev2.70154","DOIUrl":"10.1002/jev2.70154","url":null,"abstract":"<p>Small extracellular vesicles (sEV) are a class of natural vesicles rich in heterogeneous cargos with the great advantage of non-invasive detection; these vesicles exhibit complex intercellular crosstalk and mediate important biological functions. However, the potential value of plasma sEV in clinical prognosis prediction of triple-negative breast cancer (TNBC) and their biological functions have not been well elucidated. In this study, we isolated sEV from non-metastatic and metastatic TNBC plasma samples. We found that the expression of reticulin 4 (RTN4) in metastatic patients was significantly higher than that in non-metastatic patients. At the same time, clinical data showed that RTN4 was associated with poor prognosis and advanced-stage TNBC patients. Subsequently, in vivo and in vitro assays showed that compared to RTN4<sup>Low</sup> sEV, RTN4<sup>high</sup> sEV significantly promoted tumour cell migration, invasion, epithelial-mesenchymal transition (EMT) and lung metastasis, and upregulated the expression of PD-L1 in tumour tissues and inhibited CD8<sup>+</sup>T cell infiltration. Regarding mechanism research, we found that RTN4 within sEV drives tumour EMT and PD-L1 expression by activating the NF-κB signalling pathway. Further, through the combined treatment experiment of anti-PD-1 and anti-RTN4, it was found that the combination of the two drugs was significantly superior to monotherapy in inhibiting tumour metastasis, EMT, and promoting CD8<sup>+</sup>T cell infiltration. Our results highlight the molecular mechanism of sEV protein RTN4 in tumour progression and immune system regulation, indicating that RTN4 targeting and anti-PD-1 combined therapy have clinical potential. sEV protein RTN4 is a potential new prognostic marker for non-invasive detection of TNBC and a new target for TNBC treatment.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 8","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://isevjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70154","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144869699","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}
引用次数: 0
Syntenin Controls Extracellular Vesicle-Induced Tumour Migration by Regulating the Expression of Adhesion Proteins on Small Extracellular Vesicles Syntenin通过调节细胞外小泡上粘附蛋白的表达来控制细胞外小泡诱导的肿瘤迁移
IF 14.5 1区 医学
Journal of Extracellular Vesicles Pub Date : 2025-08-20 DOI: 10.1002/jev2.70133
Barnabas Irmer, Allegra Angenendt, Luc Camoin, Stéphane Audebert, Christiane Geyer, Mirjam Gerwing, Hanna Spiessbach, Mira Hebel, Émilie Baudelet, Darius Wlochowitz, Uwe Hansen, Annalen Bleckmann, Pascale Zimmermann, Kerstin Menck
{"title":"Syntenin Controls Extracellular Vesicle-Induced Tumour Migration by Regulating the Expression of Adhesion Proteins on Small Extracellular Vesicles","authors":"Barnabas Irmer,&nbsp;Allegra Angenendt,&nbsp;Luc Camoin,&nbsp;Stéphane Audebert,&nbsp;Christiane Geyer,&nbsp;Mirjam Gerwing,&nbsp;Hanna Spiessbach,&nbsp;Mira Hebel,&nbsp;Émilie Baudelet,&nbsp;Darius Wlochowitz,&nbsp;Uwe Hansen,&nbsp;Annalen Bleckmann,&nbsp;Pascale Zimmermann,&nbsp;Kerstin Menck","doi":"10.1002/jev2.70133","DOIUrl":"10.1002/jev2.70133","url":null,"abstract":"<p>Despite extensive proof for the tumour-supporting function of cancer-derived small extracellular vesicles (sEVs), attributions of pathological effects to specific sEV subpopulations are poorly described. In this study, we aimed to characterise a distinct sEV species under the control of Syntenin, a key regulator of endosomal sEV biogenesis, regarding its proteomic cargo and pro-tumourigenic functions. Using mass spectrometry (MS), we detected 178 down- and 236 up-regulated proteins on sEVs from breast cancer cells upon Syntenin knockout (KO). Pathway enrichment analysis suggested that Syntenin depletion was particularly associated with adhesion-related processes. Accordingly, sEVs from Syntenin-deficient 4T1 and MCF-7 breast cancer cells showed a reduced expression of several focal adhesion and cell–cell junction proteins. Syntenin silencing reduced the Fibronectin-binding capacity of sEVs from both cell lines, which was mediated by sEV-associated Integrin alpha-V/beta-3 (α<sub>V</sub>β<sub>3</sub>). Compared to sEVs from wildtype cells, Syntenin KO sEVs showed decreased tropism towards the Fibronectin-rich liver microenvironment in vivo, provided less adhesive support for 4T1 cells and thereby failed to induce cancer cell migration, which appeared to be independent of EV uptake. In summary, this study revealed that Syntenin has a large-scale effect on the proteomic cargo of sEVs and regulates their adhesive, organotropic and pro-migratory properties in breast cancer.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 8","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://isevjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70133","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144869700","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}
引用次数: 0
X-Ray Irradiation of Pseudomonas aeruginosa Induces Biogenesis of Outer-Inner Membrane Vesicles With Potential as a Vaccine Against Acute Pneumonia x射线照射铜绿假单胞菌诱导膜外-内膜小泡生物发生,有望作为急性肺炎疫苗
IF 14.5 1区 医学
Journal of Extracellular Vesicles Pub Date : 2025-08-18 DOI: 10.1002/jev2.70151
Li Zhang, Zhixue Shen, Yanwei Chen, Cuicui Ma, Mi Huang, Yueyue He, Guilan Wang, Dan Huang, Bo Su, Boguang Jiang, Yingjie Luo, Wenfang Li, Mao Lian, Xiaolong Xu, Xingjun Cheng, Zhenling Wang
{"title":"X-Ray Irradiation of Pseudomonas aeruginosa Induces Biogenesis of Outer-Inner Membrane Vesicles With Potential as a Vaccine Against Acute Pneumonia","authors":"Li Zhang,&nbsp;Zhixue Shen,&nbsp;Yanwei Chen,&nbsp;Cuicui Ma,&nbsp;Mi Huang,&nbsp;Yueyue He,&nbsp;Guilan Wang,&nbsp;Dan Huang,&nbsp;Bo Su,&nbsp;Boguang Jiang,&nbsp;Yingjie Luo,&nbsp;Wenfang Li,&nbsp;Mao Lian,&nbsp;Xiaolong Xu,&nbsp;Xingjun Cheng,&nbsp;Zhenling Wang","doi":"10.1002/jev2.70151","DOIUrl":"10.1002/jev2.70151","url":null,"abstract":"<p>Many bacteria produce extracellular vesicles (EVs) that play critical roles in various biological processes and hold significant potential for biomedical applications. However, the mechanisms underlying EV biogenesis remain incompletely understood. Using transmission electron microscopy, we demonstrate that X-ray irradiation induces outward blebbing of the inner membrane in <i>Pseudomonas aeruginosa</i> PAO1 (<i>P. aeruginosa</i> PAO1), leading to the formation of outer-inner membrane vesicles (OIMVs) through outer membrane pinching-off. The endolysin Lys, which is negatively regulated by PrtR and positively regulated by PrtN, is essential for OIMV production. Lys translocates into the periplasmic space, where it disrupts the peptidoglycan layer, causing morphological changes from rod-shaped to round cells and facilitating OIMV release. Furthermore, deletion of YciB, a protein crucial for inner membrane integrity, significantly increases OIMV production. In a murine model of acute pneumonia, OIMV immunisation significantly improves pulmonary bacterial clearance, reduces lung injury and enhances survival rates. Our findings reveal inner membrane blebbing as a novel mechanism of OIMV biogenesis in <i>P. aeruginosa</i> PAO1 under X-ray irradiation and highlight the potential of OIMVs as promising vaccine candidates against <i>P. aeruginosa</i> infections.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 8","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://isevjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70151","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144869459","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}
引用次数: 0
Sublytic Activity of a Pore-Forming Protein From Commensal Bacteria Causes Epigenetic Modulation of Tumour-Affiliated Protein Expression 来自共生菌的一种成孔蛋白的亚溶活性导致肿瘤相关蛋白表达的表观遗传调控
IF 14.5 1区 医学
Journal of Extracellular Vesicles Pub Date : 2025-08-18 DOI: 10.1002/jev2.70149
Eric Toh, Palwasha Baryalai, Aftab Nadeem, Kyaw Min Aung, Si Lhyam Myint, Nikola Zlatkov, Hadis Alidadi, Shaochun Zhu, André Mateus, Deepak Bushan Raina, Madeleine Ramstedt, Bernt Eric Uhlin, Sun Nyunt Wai
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