Journal of Extracellular Vesicles最新文献

{"title":"M2 Macrophage-Derived Small Extracellular Vesicle miR-106a-Loaded QCG Hydrogel Targets the RNF128-LXR Pathway to Reprogram Chondrocyte Cholesterol Metabolism for Osteoarthritis Therapy","authors":"Baozhe Liu,&nbsp;Zhan Wang,&nbsp;Jingyong Zhang,&nbsp;Wei Du,&nbsp;Lifeng Ding,&nbsp;Shang Piao","doi":"10.1002/jev2.70386","DOIUrl":"10.1002/jev2.70386","url":null,"abstract":"<p>This study addresses osteoarthritis (OA), in which dysregulated chondrocyte cholesterol homeostasis and cellular senescence contribute to cartilage degeneration, by developing an inflammation-responsive injectable QCG hydrogel for local delivery of miR-106a-enriched M2 macrophage-derived small extracellular vesicles (sEVs). The QCG hydrogel was constructed from quaternized chitosan (QCS) and 4-carboxyphenylboronic acid-gelatin (CPBA-gelatin) and loaded with miR-106a-enriched M2-sEVs (QCG@sEV-miR-106a). M2-sEVs were isolated by differential ultracentrifugation and characterized by transmission electron microscopy, nanoparticle tracking analysis, and vesicle-associated protein markers. High-throughput miRNA profiling and chondrocyte RNA sequencing identified miR-106a as a candidate regulatory molecule, and RNF128 was confirmed as a direct target by dual-luciferase reporter assay. Functional experiments showed that miR-106a suppresses RNF128, thereby promoting chondrocyte proliferation and extracellular matrix synthesis while attenuating senescence. Exploratory proteomic screening suggested RNF128-associated changes in cholesterol- and lysosome-related processes, whereas independent molecular and functional assays demonstrated that RNF128 promotes LXRα ubiquitination and proteasome-dependent degradation, suppresses LXR signaling, and disrupts cholesterol homeostasis. In a destabilization of the medial meniscus (DMM)-induced OA rat model, QCG@sEV-miR-106a showed ROS-responsive release, prolonged intra-articular retention for up to 22 days, reduced cartilage degeneration and matrix loss, improved pain-related behaviors, and favorable short-term biocompatibility. Together, these findings support a local biomaterial delivery strategy in which miR-106a-mediated RNF128 inhibition preserves LXR signaling and cholesterol homeostasis to attenuate OA-associated chondrocyte senescence.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 10","pages":""},"PeriodicalIF":21.7,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13653648/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164560","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":"Agrin-Enriched Neonatal Spinal Cord-Derived Extracellular Vesicles Bypass Age Barriers to Organize Spinal Cord Repair","authors":"Yongfeng Zhang,&nbsp;Qi Liu,&nbsp;Beibei Yu,&nbsp;Borui Xue,&nbsp;Shijie Yang,&nbsp;Teng Ma,&nbsp;Lingli Guo,&nbsp;Haining Wu,&nbsp;Xue Gao,&nbsp;Shengyou Li,&nbsp;Yujie Yang,&nbsp;Yiming Hao,&nbsp;Ziqing Zhu,&nbsp;Meijia Su,&nbsp;Hongyu Li,&nbsp;Shuanshuan Fan,&nbsp;Jiaqi Wang,&nbsp;Huangtao Chen,&nbsp;Longhui Fu,&nbsp;Anhui Qin,&nbsp;Zhenguo Wang,&nbsp;Shihao Nie,&nbsp;Mingze Qin,&nbsp;Xinxin Bai,&nbsp;Guang Kong,&nbsp;Rui Zhao,&nbsp;Dong Lei,&nbsp;Yue Yu,&nbsp;Junxiong Ma,&nbsp;Shouping Gong,&nbsp;Bing Xia,&nbsp;Jinghui Huang","doi":"10.1002/jev2.70371","DOIUrl":"10.1002/jev2.70371","url":null,"abstract":"<p>Spinal cord injury (SCI) poses a formidable challenge in regenerative medicine, with current therapeutic strategies proving largely unsuccessful in achieving functional repair. Notably, paediatric patients and neonatal mice exhibit spontaneous and efficient regeneration after SCI, while the mechanisms remain elusive. Through integrated multi-omics analysis in neonatal, adult and aged mice with SCI, we discovered that the regeneration time window, inflammatory response, and intercellular communication are all age-dependent. Neonatal spinal cord-derived extracellular vesicles (nSC-EVs) were identified carrying a regenerative protein signature and were critical mediators in restoring SCI repair in neonatal mice. Functionally, nSC-EVs promote neurogenesis <i>via</i> the Wnt/β-catenin pathway and mediate axonal growth through the core effector Agrin (encoded by <i>Agrn</i>), which was found to be predominantly expressed in endothelial cells. We further developed a targeted delivery system for nSC-EVs, which significantly enhanced functional recovery, including motor and bladder control, in adult SCI mice. This work elucidates the mechanistic basis of age-dependent repair processes and proposes a novel EV-based therapy for SCI.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 10","pages":""},"PeriodicalIF":21.7,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13653649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149166866","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":"Tissue-Specific Isolation of Hepatocyte Extracellular Vesicles From Human Plasma Enables Tissue-Resolved Proteomic and miRNA Profiling","authors":"Ricardo Figueiras,&nbsp;Susana Vagueiro,&nbsp;Raissa Kay,&nbsp;Elnaz Persia,&nbsp;Roger de Alwis,&nbsp;Razan Hijazi,&nbsp;Brian Davidson,&nbsp;Kristine von Bargen,&nbsp;Pierre Arsène,&nbsp;Tomás Dias","doi":"10.1002/jev2.70372","DOIUrl":"10.1002/jev2.70372","url":null,"abstract":"<p>Tissue-specific resolution remains a critical barrier in liquid biopsy for precision medicine. To address this, we developed NEXPLOR (Novel EXtracellular vesicle PopuLation Omics Revealer), an immunoaffinity platform enabling selective enrichment of circulating tissue-specific extracellular vesicles (TS-EVs), demonstrated here for liver-derived hepatocyte-EVs (h-EVs). Through in silico discovery and orthogonal antibody validation across tissues, we identified a four-marker panel (ASGR1, ASGR2, TFR2, SLCO1B1) that selectively enriched hepatocyte EVs without co-capturing the dominant platelet- and leukocyte-EV background. In a clinical cohort of hepatocellular carcinoma (HCC), non-cancer cirrhosis and healthy donors, NEXPLOR recovered 57% more proteins than bulk EV isolation, with greater reproducibility. By restoring tissue context, h-EVs exposed liver biology that bulk EVs miss, spanning three levels: metabolic pathways (carbon metabolism, HIF-1α signalling, ferroptosis), HCC-defining proteins (PGD, H2AZ1, PRDX5), and progression-tracking candidates (CFB, PCSK9). Small RNA sequencing detected five miRNAs upregulated in HCC versus cirrhosis h-EVs, against 21 in bulk EVs (no overlap); yet only the h-EV miRNAs mapped to HCC-relevant signalling, and hepatocyte-regulatory miR-124-3p appeared exclusively in h-EVs. Together, these results establish tissue-specific EV enrichment as a route to more actionable, multi-omic liquid biopsies in HCC, cirrhosis and other diseases in urgent need of non-invasive biomarkers for patient diagnosis, monitoring and stratification.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 10","pages":""},"PeriodicalIF":21.7,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13653647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149168111","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":"MVB Maturation Responsive to KRASG12D/TP53R175H Co-mutations Fuels Extracellular Vesicle-hypersecretion Phenotype to Aggravate Lymphangiogenesis and Lymphatic Metastasis","authors":"Jiabin Yang,&nbsp;Yuming Luo,&nbsp;Yu Zhou,&nbsp;Mingjie An,&nbsp;Mingrui Pang,&nbsp;Zhihua Li,&nbsp;Qingyu Xie,&nbsp;Hanhao Zheng,&nbsp;Zhou Fang,&nbsp;Yao Kong,&nbsp;Chao Yu,&nbsp;Yan Lin,&nbsp;Dingwen Zhang,&nbsp;Bingxin Cao,&nbsp;Haoming Zhong,&nbsp;Changhao Chen,&nbsp;Rufu Chen","doi":"10.1002/jev2.70383","DOIUrl":"10.1002/jev2.70383","url":null,"abstract":"<p>KRAS<i>^G12D</i>/TP53<i>^R175H</i> mutations are hallmarks of malignant tumor progression and are associated with lymph node (LN) metastasis in solid tumor. Nevertheless, the mechanisms underlying KRAS<i>^G12D</i>/TP53<i>^R175H</i> co-mutation-mediated LN metastasis remain unclear. Herein, we developed KRAS<i>^G12D</i>/TP53<i>^R175H</i> mutation-related orthotopic xenograft models and demonstrated that KRAS<i>^G12D</i>/TP53<i>^R175H</i> co-mutation promotes the lymphangiogenesis and LN metastasis. FUS is identified by next generation sequencing to be upregulated in tumor tissues harbouring KRAS<i>^G12D</i>/TP53<i>^R175H</i> co-mutation across multi-center cohorts, wherein KRAS<i>^G12D</i>-mediated phosphorylation of TP53<i>^R175H</i> promotes FUS transcriptional activation. Functionally, FUS-mediated extracellular vesicle (EV) promotes lymphangiogenesis and LN metastasis <i>in vitro</i> and <i>in vivo</i>. Mechanistically, upon KRAS<i>^<i>G12D</i></i>/TP53<i>^<i>R175H</i></i> co ‑ mutation, FUS regulated circSCARNA10 biosynthesis and promotes EVs secretion by stabilizing RAB3B mRNA, leading to VEGFR3 transcription in lymphatic endothelial cells to trigger lymphangiogenesis and LN metastasis. Blockade of FUS inhibits LN metastasis in Kras<i>^G12D/+</i>Trp53<i>^R172H/+</i>Pdx-1-Cre (KPC) mice model. Clinically, detecting circSCARNA10 in serum-EVs exhibited higher diagnostic efficiency compared with traditional biomarkers, carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) in distinguishing LN metastasis. Collectively, we highlight the precise mechanisms by which KRAS<i>^G12D</i>/TP53<i>^R175H</i> co-mutation mediates EV secretion to trigger LN metastasis, providing a potential therapeutic target for KRAS<i>^G12D</i>/TP53<i>^R175H</i> co-mutation - driven LN metastasis.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 10","pages":""},"PeriodicalIF":21.7,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13653645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149165721","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":"Heparin Can Augment Extracellular Vesicle Yield by Inhibiting Reuptake in Donor Cells During Cell Propagation","authors":"André Cronemberger Andrade,&nbsp;Rodolphe Poupardin,&nbsp;Martin Wolf,&nbsp;Liliia Paniushkina,&nbsp;Karim Selmi,&nbsp;Deepika Kundully Suresh,&nbsp;Nicole Maeding,&nbsp;Heide-Marie Binder,&nbsp;Janine Zwicklhuber,&nbsp;Sarah Hochmann,&nbsp;André Görgens,&nbsp;Samir El Andaloussi,&nbsp;Katharina Schallmoser,&nbsp;Dirk Strunk","doi":"10.1002/jev2.70382","DOIUrl":"10.1002/jev2.70382","url":null,"abstract":"<p>Extracellular vesicles (EVs) mediate cell-to-cell communication in development, health and disease. Heparin is a common component in human induced pluripotent stem cell (hiPSC) media but its impact on hiPSC-EVs beyond stabilizing growth factors is unknown. Published evidence indicates heparin dose-dependent EV uptake inhibition in heterotypic target cells. We asked if heparin affects hiPSC-EV yield, storage, phenotype, or function. We used large-scale hiPSC-EV propagation to obtain pro-angiogenic hiPSC-EVs in presence or absence of escalating heparin doses and determined EV quantity, identity and functionality. Heparin delayed hiPSC colony-confluence without significantly affecting hiPSC viability, pluripotency markers and proliferation. Significantly elevated tetraspanin⁺/flotillin⁺ hiPSC-EV number (mean 367±31 EVs/cell/24 h at 200 IU heparin/mL) enabled efficient purification of &gt; 10¹¹/mL functional EVs at superior particle/protein ratio &gt; 10¹⁰/mg. Heparin dose-dependently inhibited EV uptake in hiPSC and endothelial progenitors, comparable to 5 IU/mL flavobacterium heparinase, and increased EV recovery after storage in NaCl but not in cell-conditioned media. EVs obtained from hiPSC at 1% O₂ with 200 IU/mL heparin maintained superior angiogenesis similarly to control hiPSC-EVs obtained without heparin. We conclude that heparin inhibits hiPSC-EV reuptake and stabilizes NaCl-cryopreserved EVs thus boosting EV recovery while maintaining pro-angiogenic function. Heparin presence and dose should therefore be documented particularly in PSC media.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 10","pages":""},"PeriodicalIF":21.7,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13653646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149166931","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":"C1qc Mediates Blood–Brain Barrier Disruption in a Mouse Model of Intracerebral Haemorrhage Through Microglia-Derived Migrasomes","authors":"Mengyuan Li,&nbsp;Zhihua Li,&nbsp;Dengpan Song,&nbsp;Fang Wang,&nbsp;Mengzhao Feng,&nbsp;Chi-Tai Yeh,&nbsp;Tingting Zhai,&nbsp;Menghan Deng,&nbsp;Yanyan Sun,&nbsp;Junyang Wang,&nbsp;Xuemei Chen,&nbsp;Yating Wang,&nbsp;Qiong Yang,&nbsp;Moxin Wu,&nbsp;Xiaoping Yin,&nbsp;Junmin Wang,&nbsp;Jian Wang,&nbsp;Fuyou Guo","doi":"10.1002/jev2.70377","DOIUrl":"10.1002/jev2.70377","url":null,"abstract":"<p>Extracellular vesicles (EVs) are essential for intercellular communication and significantly influence neuroimmune responses after intracerebral haemorrhage (ICH). This study elucidates the immune mechanisms underlying secondary brain injury following ICH by identifying microglia-derived migrasomes. By integrating immune cell clustering analysis from single-cell RNA sequencing (scRNA-seq) with Mendelian randomization, we identified five key genes associated with ICH. Further experiments revealed that C1qc accumulates around hematomas, worsening blood‒brain barrier (BBB) disruption through migrasome-mediated pathways. Our results showed that microglial migrasomes transport C1qc to induce pyroptosis in vascular endothelial cells, thereby compromising BBB integrity. Genetic ablation of C1qc substantially attenuated this BBB damaging effect, C1qc-deficient migrasomes exhibited protective properties. Our findings, for the first time, reveal the mechanistic role of C1qc and migrasomes in ICH pathogenesis and establish microglia-derived migrasomes as promising therapeutic targets, providing novel avenues to improve neurologic outcomes after ICH.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 10","pages":""},"PeriodicalIF":21.7,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70377","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127567","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":"Longitudinally Monitoring Prostate Cancer Bone Metastasis and Treatment Response via Circulating Extracellular Vesicles","authors":"Emanuela Gentile,&nbsp;Paul G. Corn,&nbsp;Martha Zavridou,&nbsp;James P. Long,&nbsp;Jian H. Song,&nbsp;Anh Hoang,&nbsp;Andrew W. Hahn,&nbsp;Eleonora Dondossola,&nbsp;William Norton,&nbsp;Sue-Hwa Lin,&nbsp;Christopher J. Logothetis,&nbsp;Theocharis Panaretakis","doi":"10.1002/jev2.70364","DOIUrl":"10.1002/jev2.70364","url":null,"abstract":"<p>Lethal prostate cancer (PCa) is dominated by treatment-refractory progression in bone. In this study, we used plasma-derived extracellular vesicles (EVs) for monitoring the tumour and therapy-induced changes in the bone tumour microenvironment (bone-TME) in men with bone metastatic PCa (M1b PCa). Transcriptome analysis of differentially expressed genes in plasma EVs from patients with M1b and localized (M0) PCa, identified a ‘bone metastasis signature’ (BMS) that reflects tumour-induced bone formation. In preclinical studies, the BMS was enriched in plasma EVs from mice inoculated with bone-metastatic MDA PCa-118b but not with adrenal-metastatic MDA PCa-250 tumours. Longitudinal monitoring of the BMS for up to 50 days showed that the levels of several genes increased prior to detectable growth of bone-forming tumours. Real-time monitoring of the BMS from tumour-bearing mice treated with the bone-targeting agent Ra-223 showed reduction of their expression that correlated with reduction in bone formation and tumour growth. Development of resistance to Ra-223 correlated with the induction of the BMS genes. In a cohort of PCa patients with clinically localized PCa with pathologic lymph node involvement, increases in BMS genes following hormonal therapy correlated with the subsequent development of metastasis during long term follow up. The BMS may enable longitudinal monitoring of the initiation, progression and treatment response of M1b PCa.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 10","pages":""},"PeriodicalIF":21.7,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70364","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127731","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":"Extracellular Vesicle-Bound Bacterial Toxin Pneumolysin Triggers Membrane Engagement and Damage Beyond Canonical Pore Formation","authors":"Aswathy C. Sagilkumar,&nbsp;Avinashi Lal Kushwaha,&nbsp;Anushka Shitut,&nbsp;Dheeraj Kumar Sarkar,&nbsp;Sruthika Sukumar,&nbsp;Subhajit Mahanty,&nbsp;Somnath Dutta,&nbsp;Jagannath Mondal,&nbsp;Karthik Subramanian","doi":"10.1002/jev2.70387","DOIUrl":"10.1002/jev2.70387","url":null,"abstract":"<p>Pneumolysin (PLY) is a cholesterol-dependent pore-forming toxin and a key virulence factor of <i>Streptococcus pneumoniae</i>, the leading cause of pneumonia worldwide in children aged below 5 years. At sublytic toxin doses, host cells shed PLY-laden extracellular vesicles (EVs) during the membrane repair response. However, it remains unclear how these toxin-bearing EVs engage and damage target cell membranes. Here, we combine molecular dynamics simulations, liposome fusion assays and cell-based experiments to elucidate the membrane interaction potential of vesicle-bound PLY. Simulations indicate that EV-embedded PLY uses an exposed helix to bind target cell membranes, inducing pronounced curvature, bilayer thinning and water influx. Liposome fusion assays by 3D confocal imaging and Cryo-EM analysis demonstrate that both PLY and membrane cholesterol promote vesicle-membrane interactions. Characterisation of vesicle subpopulations released from PLY-challenged monocytes by western blotting and immunogold electron microscopy demonstrated that plasma membrane-derived microvesicles are preferentially enriched in membrane-bound PLY compared to small extracellular vesicles. Consistent with these findings, MVs purified from wild-type PLY-challenged monocytes, fuse with human peripheral blood mononuclear cells, delivering toxin and causing membrane damage, which was significantly lower with the toxoid mutant, PLYW433F. Among PBMCs, CD4⁺ T cells showed higher PLY positivity upon MV co-incubation and higher cell death compared to monocytes at same dose. Together, our results reveal a noncanonical mode of toxin dissemination, in which vesicle-bound pneumolysin fuses and destabilises target cell membranes, representing an alternative pathway for EV-mediated toxin activity and a potential target for therapeutic intervention.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 10","pages":""},"PeriodicalIF":21.7,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13626481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149110620","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":"Bacterial Cytochrome C Orchestrates Larval Metamorphosis Through Bioelectrical Control of Extracellular Vesicles Biogenesis","authors":"Yu Tao,&nbsp;Li-Hua Peng,&nbsp;Jinqi Hou,&nbsp;Yuyi Wang,&nbsp;Jingxiang Xu,&nbsp;Jin-Long Yang,&nbsp;Xiao Liang","doi":"10.1002/jev2.70373","DOIUrl":"10.1002/jev2.70373","url":null,"abstract":"<p>Beyond the well-established roles in biomedical processes, extracellular vesicles (EVs) from Gram-negative bacteria are now identified as potent inducers of larval metamorphosis in marine invertebrates, a critical process for sustaining the health and function of global marine ecosystems. However, the specific inductive molecules within EVs remain largely unknown. Our findings reveal that cytochrome c (CytC), a previously unrecognized chemical signal packaged within EVs, induces larval metamorphosis. CytC maturation is essential for this process, as it enhances the efficiency of electron transfer, thereby supplying the energy required for EV biogenesis and loading with CytC cargo. Molecular docking analysis suggests that bacterial CytC induces the metamorphosis of mussels by binding to Toll-like receptor 4 (TLR4). Notably, a marked rise in CytC gene abundance was observed in the associated bacterial community during larval metamorphosis, which may indicate a programmed enhancement of electrogenic activity within the biofilm microenvironment to support larval developmental transition. Overall, a new paradigm for interkingdom signaling is proposed in this study, wherein CytC serves as a bioelectrical driver of EV biogenesis and a potentially broadly acting inductive signal within EVs for larval metamorphosis in invertebrates.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 10","pages":""},"PeriodicalIF":21.7,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13626770/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149110635","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":"Enrichment and Proteomic Profiling of Stromal-Associated Extracellular Vesicle Subpopulations From Arthritic Synovial Fluid by Size-Exclusion Chromatography Coupled to CD90-Directed Immunocapture","authors":"Stefanie Kurth,&nbsp;Edveena Hanser,&nbsp;Simone Häner-Massimi,&nbsp;Stavros Giaglis,&nbsp;Florian Geier,&nbsp;Dominik Burri,&nbsp;Katarzyna Buczak,&nbsp;Ute Heider,&nbsp;Stefan Wild,&nbsp;Yves P. Acklin,&nbsp;Christian Egloff,&nbsp;André N. Tiaden,&nbsp;Diego Kyburz","doi":"10.1002/jev2.70353","DOIUrl":"10.1002/jev2.70353","url":null,"abstract":"<p>Extracellular vesicles (EVs) are emerging as key mediators of disease-associated intercellular communication and as promising biomarker sources across many disease conditions, including joint disorders such as rheumatoid arthritis (RA) and osteoarthritis (OA). Molecular profiling of synovial tissue has uncovered disease-driving cellular states, but tissue biopsies are invasive and not routinely available. EVs in synovial fluid may offer a minimally invasive and complementary window into joint pathobiology. However, the molecular complexity of synovial fluid and the heterogeneity of EV populations have hindered the analysis of defined disease-relevant EV subsets. To address this challenge, we developed a refined size-exclusion chromatography-ultrafiltration (SEC-UF) workflow coupled to magnetic bead-based immunocapture for targeted enrichment of cell type-associated EV subpopulations from arthritic synovial fluid. As proof-of-concept, we targeted a stromal-associated EV population using CD90/THY1, a surface marker expressed by discrete synovial fibroblasts subsets implicated in arthritis pathobiology. In vitro validation using synovial fibroblast-derived EVs confirmed surface-accessible CD90 and demonstrated selective immunocapture of defined EV subpopulations. Application to patient-derived synovial fluid showed that SEC-UF pre-enrichment improves the robustness of CD90⁺ EV recovery from this complex biofluid. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) profiling established broad EV-associated proteome coverage in synovial fluid (SF)-EV preparations and identified multiple proteins reflecting the inflamed arthritic synovial environment. Fraction-resolved proteomics enabled comparison of the CD90-immunocaptured SF-EV subset with the non-captured CD90⁻/CD90^low SF-EV pool. Differential proteomics and surfaceome-informed cell-of-origin analysis supported enrichment of stromal-associated surface markers in the CD90⁺ fraction, whereas the non-captured SF-EV pool retained broader immune-associated and residual stromal EV inputs. Together, this fit-for-purpose workflow provides a strategy to resolve EV heterogeneity patient synovial fluid and supports future biomarker-oriented studies of defined subpopulations in arthritic diseases.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 10","pages":""},"PeriodicalIF":21.7,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13626482/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149110666","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}