Journal of Extracellular Vesicles最新文献

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Evaluation of unmodified human cell-derived extracellular vesicle mitochondrial deoxyribonucleic acid-based biodistribution in rodents 在啮齿动物体内评估基于线粒体脱氧核糖核酸的未修饰人细胞衍生细胞外囊泡生物分布。
IF 15.5 1区 医学
Journal of Extracellular Vesicles Pub Date : 2024-07-17 DOI: 10.1002/jev2.12489
Young-Woo Cho, Mi Young Cho, Jaehyeon Yoon, Da Eun Hong, Ju-young Lee, Hye Sun Park, Hyunseung Lee, Kwan Soo Hong, Lee Won-Kyu, Choi Saehae, Suk-Gil Song, Young-Woock Noh
{"title":"Evaluation of unmodified human cell-derived extracellular vesicle mitochondrial deoxyribonucleic acid-based biodistribution in rodents","authors":"Young-Woo Cho,&nbsp;Mi Young Cho,&nbsp;Jaehyeon Yoon,&nbsp;Da Eun Hong,&nbsp;Ju-young Lee,&nbsp;Hye Sun Park,&nbsp;Hyunseung Lee,&nbsp;Kwan Soo Hong,&nbsp;Lee Won-Kyu,&nbsp;Choi Saehae,&nbsp;Suk-Gil Song,&nbsp;Young-Woock Noh","doi":"10.1002/jev2.12489","DOIUrl":"10.1002/jev2.12489","url":null,"abstract":"<p>Recently, extracellular vesicles (EVs) have been developed as therapeutic targets for various diseases. Biodistribution is crucial for EVs intended for therapeutic purposes because it can determine the degree of on- and off-target effects. This study aimed to explore techniques to evaluate the biodistribution of unmodified EVs. We devised a novel quantitative polymerase chain reaction (qPCR)-based assay to detect unmodified EVs by targeting mitochondrial deoxyribonucleic acid (mtDNA), a constituent of EVs. We focused on specific mtDNA regions that exhibited homologous variations distinct from their rodent mtDNA counterparts to establish this analytical approach. Herein, we successfully designed primers and probes targeting human and rodent mtDNA sequences and developed a highly specific and sensitive qPCR method. Furthermore, the quantification range of EVs isolated from various cells differed based on the manufacturer and cell source. IRDye 800CW-labelled Expi293F EV mimetics were administered to the animals via the tail vein to compare the imaging test and mtDNA-qPCR results. The results obtained from imaging tests and mtDNA-qPCR to investigate EV biodistribution patterns revealed differences. The results revealed that our newly developed method effectively determined the biodistribution of unmodified EVs with high sensitivity and reproducibility.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"13 7","pages":""},"PeriodicalIF":15.5,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.12489","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141626886","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
CD66b+/CD68+ circulating extracellular vesicles, lactate dehydrogenase and neutrophil-to-lymphocyte ratio can differentiate coronavirus disease 2019 severity during and after infection CD66b+/CD68+循环细胞外囊泡、乳酸脱氢酶和中性粒细胞与淋巴细胞的比率可在感染期间和感染后区分冠状病毒病2019年最新注册送彩金的严重程度。
IF 15.5 1区 医学
Journal of Extracellular Vesicles Pub Date : 2024-07-15 DOI: 10.1002/jev2.12456
Rosa Suades, Maria Francesca Greco, Paula Prieto, Teresa Padró, Yvan Devaux, Pere Domingo, Lina Badimon
{"title":"CD66b+/CD68+ circulating extracellular vesicles, lactate dehydrogenase and neutrophil-to-lymphocyte ratio can differentiate coronavirus disease 2019 severity during and after infection","authors":"Rosa Suades,&nbsp;Maria Francesca Greco,&nbsp;Paula Prieto,&nbsp;Teresa Padró,&nbsp;Yvan Devaux,&nbsp;Pere Domingo,&nbsp;Lina Badimon","doi":"10.1002/jev2.12456","DOIUrl":"10.1002/jev2.12456","url":null,"abstract":"<p>Coronavirus disease 2019 (COVID-19) has been a major public health burden. We hypothesised that circulating extracellular vesicles (cEVs), key players in health and disease, could trace the cell changes during COVID-19 infection and recovery. Therefore, we studied the temporal trend of cEV and inflammatory marker levels in plasma samples of COVID-19 patients that were collected within 24 h of patient admission (baseline, <i>n</i> = 80) and after hospital discharge at day-90 post-admission (<i>n</i> = 59). Inflammatory markers were measured by standard biochemical methods. cEVs were quantitatively and phenotypically characterized by high-sensitivity nano flow cytometry. In patients recovered from COVID-19 lower levels of inflammatory markers were detected. cEVs from vascular (endothelial cells) and blood (platelets, distinct immune subsets) cells were significantly reduced at day-90 compared to admission levels, a pattern also observed for cEVs from progenitor, perivascular and epithelial cells. The best discriminatory power for COVID-19 severity was found for inflammatory markers lactate dehydrogenase and neutrophil-to-lymphocyte ratio and for granulocyte/macrophage-released CD66b<sup>+</sup>/CD68<sup>+</sup>-cEVs. Albeit inflammatory markers were good indicators of systemic inflammatory response and discriminators of COVID-19 remission, they do not completely reveal cell stress and organ damage states. cEVs reaching baseline pre-infection levels at 90 days post-infection in recovered patients discriminate parental cells affected by disease.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"13 7","pages":""},"PeriodicalIF":15.5,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.12456","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141616603","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
Extracellular vesicles from seminal plasma interact with T cells in vitro and drive their differentiation into regulatory T-cells 精浆中的细胞外囊泡在体外与 T 细胞相互作用,促使它们分化为调节性 T 细胞。
IF 15.5 1区 医学
Journal of Extracellular Vesicles Pub Date : 2024-07-15 DOI: 10.1002/jev2.12457
Xiaogang Zhang, Patrick F. Greve, Thi Tran Ngoc Minh, Richard Wubbolts, Ayşe Y. Demir, Esther A. Zaal, Celia R. Berkers, Marianne Boes, Willem Stoorvogel
{"title":"Extracellular vesicles from seminal plasma interact with T cells in vitro and drive their differentiation into regulatory T-cells","authors":"Xiaogang Zhang,&nbsp;Patrick F. Greve,&nbsp;Thi Tran Ngoc Minh,&nbsp;Richard Wubbolts,&nbsp;Ayşe Y. Demir,&nbsp;Esther A. Zaal,&nbsp;Celia R. Berkers,&nbsp;Marianne Boes,&nbsp;Willem Stoorvogel","doi":"10.1002/jev2.12457","DOIUrl":"10.1002/jev2.12457","url":null,"abstract":"<p>Seminal plasma induces immune tolerance towards paternal allogenic antigens within the female reproductive tract and during foetal development. Recent evidence suggests a role for extracellular vesicles in seminal plasma (spEVs). We isolated spEVs from seminal plasma that was donated by vasectomized men, thereby excluding any contributions from the testis or epididymis. Previous analysis demonstrated that such isolated spEVs originate mainly from the prostate. Here we observed that when isolated fluorescently labelled spEVs were mixed with peripheral blood mononuclear cells, they were endocytosed predominantly by monocytes, and to a lesser extent also by T-cells. In a mixed lymphocyte reaction, T-cell proliferation was inhibited by spEVs. A direct effect of spEVs on T-cells was demonstrated when isolated T cells were activated by anti-CD3/CD28 coated beads. Again, spEVs interfered with T cell proliferation, as well as with the expression of CD25 and the release of IFN-γ, TNF, and IL-2. Moreover, spEVs stimulated the expression of Foxp3 and IL-10 by CD4+CD25+CD127- T cells, indicating differentiation into regulatory T-cells (Tregs). Prior treatment of spEVs with proteinase K revoked their effects on T-cells, indicating a requirement for surface-exposed spEV proteins. The adenosine A2A receptor-specific antagonist CPI-444 also reduced effects of spEVs on T-cells, consistent with the notion that the development of Tregs and their immune suppressive functions are under the influence of adenosine-A2A receptor signalling. We found that adenosine is highly enriched in spEVs and propose that spEVs are targeted to and endocytosed by T-cells, after which they may release their adenosine content into the lumen of endosomes, thus allowing endosome-localized A2A receptor signalling in spEVs targeted T-cells. Collectively, these data support the idea that spEVs can prime T cells directly for differentiation into Tregs.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"13 7","pages":""},"PeriodicalIF":15.5,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.12457","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141616604","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
ISEV2024 Abstract Book ISEV2024 摘要手册。
IF 15.5 1区 医学
Journal of Extracellular Vesicles Pub Date : 2024-07-13 DOI: 10.1002/jev2.12444
{"title":"ISEV2024 Abstract Book","authors":"","doi":"10.1002/jev2.12444","DOIUrl":"10.1002/jev2.12444","url":null,"abstract":"&lt;p&gt;The International Society for Extracellular Vesicles is the leading professional society for researchers and scientists involved in the study of microvesicles and exosomes. With nearly 1,000 members, ISEV continues to be the leader in advancing the study of extracellular vesicles. Founded in 2012 in Sweden, ISEV has since moved its Headquarters to the United States. Through its programs and services, ISEV provides essential training and research opportunities for those involved in exosome and microvesicle research.&lt;/p&gt;&lt;p&gt;Advancing extracellular vesicle research globally.&lt;/p&gt;&lt;p&gt;Our vision is to be the leading advocate and guide of extracellular vesicle research and to advance the understanding of extracellular vesicle biology.&lt;/p&gt;&lt;p&gt;The International Society for Extracellular Vesicles is the is the premier international conference of extracellular vesicle research, covering the latest in exosomes, microvesicles and more. With an anticipated 1,000+ attendees, ISEV2024 will feature presentations from the top researchers in the field, as well as providing opportunities for talks from students and early career researchers.&lt;/p&gt;&lt;p&gt;IOC Chairs: Cherie Blenkiron (New Zealand), David Greening (Australia)&lt;/p&gt;&lt;p&gt;IOC Members: Randy Carney (USA), Leslie Cheng (Australia), Eisuke Dohi (Japan), Qing-Ling Fu (China), Charles Lai (Taiwan), Metka Lenassi (Slovenia), Andreas Moeller (China), Jisook Moon (South Korea), Natalie Turner (Australia)&lt;/p&gt;&lt;p&gt;Jan Lötvall (Sweden)&lt;/p&gt;&lt;p&gt;&lt;b&gt;0T04.O02&lt;/b&gt; Cellular interaction and uptake of human endogenous retrovirus (HERV) envelope-displaying EVs&lt;/p&gt;&lt;p&gt;&lt;b&gt;&lt;span&gt;Dr. Zach Troyer&lt;/span&gt;&lt;/b&gt;, Sarah Marquez, PhD Olesia Gololobova, PhD Kenneth Witwer&lt;/p&gt;&lt;p&gt;&lt;b&gt;0T04.O03&lt;/b&gt; Functionalized engineered extracellular vesicles for targeted delivery to intervertebral disc cells&lt;/p&gt;&lt;p&gt;&lt;b&gt;&lt;span&gt;Ms Mia Kordowski&lt;/span&gt;&lt;/b&gt;, Dr Ana Salazar-Puerta, Ms María Rincon-Benavides, Mr Justin Richards, Dr Nina Tang, Dr Safdar Khan, Dr Elizabeth Yu, Dr Judith Hoyland, Dr Devina Purmessur, Dr Natalia Higuita-Castro&lt;/p&gt;&lt;p&gt;&lt;b&gt;0T04.O04&lt;/b&gt; Phospholipid scrambling: a novel regulator of extracellular vesicle cargo packaging and function&lt;/p&gt;&lt;p&gt;Ms Akbar Marzan, Ms Monika Petrovska, Professor Suresh Mathivanan, &lt;b&gt;&lt;span&gt;Sarah Stewart&lt;/span&gt;&lt;/b&gt;&lt;/p&gt;&lt;p&gt;&lt;b&gt;0T04.O05&lt;/b&gt; Quantitative features of extracellular vesicle-mediated crosstalk in multi-cellular 3D tumor models&lt;/p&gt;&lt;p&gt;&lt;b&gt;&lt;span&gt;Dr. Maria Harmati&lt;/span&gt;&lt;/b&gt;, Akos Diosdi, Ferenc Kovács, Ede Migh, Gabriella Dobra, Timea Boroczky, Matyas Bukva, Edina Gyukity-Sebestyen, Peter Horvath, Krisztina Buzas&lt;/p&gt;&lt;p&gt;&lt;b&gt;FA01&lt;/b&gt; Extracellular vesicles in human body fluids compete with virus particles for binding of phosphatidylserine receptors to prevent infection and transmission&lt;/p&gt;&lt;p&gt;&lt;b&gt;&lt;span&gt;Dr. Ruediger Gross&lt;/span&gt;&lt;/b&gt;, Hanna Reßin, Pascal von Maltitz, Dan Albers, Laura Schneider, Hanna Bley, Markus Hoffmann, Mirco Cortese, Dhanu Gupta, Miriam Deniz, Jae-Yeon Choi, Jenny Jansen, Christian Preußer, Kai Seehafer, Stefan Pö","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"13 S1","pages":""},"PeriodicalIF":15.5,"publicationDate":"2024-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.12444","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141600198","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
Characterisation of LPS+ bacterial extracellular vesicles along the gut-hepatic portal vein-liver axis 沿肠道-肝门静脉-肝轴的 LPS+ 细菌胞外囊泡的特征。
IF 15.5 1区 医学
Journal of Extracellular Vesicles Pub Date : 2024-07-13 DOI: 10.1002/jev2.12474
Heetanshi Jain, Ashish Kumar, Sameh Almousa, Shalini Mishra, Kendall L. Langsten, Susy Kim, Mitu Sharma, Yixin Su, Sangeeta Singh, Bethany A. Kerr, Gagan Deep
{"title":"Characterisation of LPS+ bacterial extracellular vesicles along the gut-hepatic portal vein-liver axis","authors":"Heetanshi Jain,&nbsp;Ashish Kumar,&nbsp;Sameh Almousa,&nbsp;Shalini Mishra,&nbsp;Kendall L. Langsten,&nbsp;Susy Kim,&nbsp;Mitu Sharma,&nbsp;Yixin Su,&nbsp;Sangeeta Singh,&nbsp;Bethany A. Kerr,&nbsp;Gagan Deep","doi":"10.1002/jev2.12474","DOIUrl":"10.1002/jev2.12474","url":null,"abstract":"<p>Gut microbiome dysbiosis is a major contributing factor to several pathological conditions. However, the mechanistic understanding of the communication between gut microbiota and extra-intestinal organs remains largely elusive. Extracellular vesicles (EVs), secreted by almost every form of life, including bacteria, could play a critical role in this inter-kingdom crosstalk and are the focus of present study. Here, we present a novel approach for isolating lipopolysaccharide (LPS)+ bacterial extracellular vesicles (bEV<sup>LPS</sup>) from complex biological samples, including faeces, plasma and the liver from lean and diet-induced obese (DIO) mice. bEV<sup>LPS</sup> were extensively characterised using nanoparticle tracking analyses, immunogold labelling coupled with transmission electron microscopy, flow cytometry, super-resolution microscopy and 16S sequencing. In liver tissues, the protein expressions of TLR4 and a few macrophage-specific biomarkers were assessed by immunohistochemistry, and the gene expressions of inflammation-related cytokines and their receptors (<i>n</i> = 89 genes) were measured using a PCR array. Faecal samples from DIO mice revealed a remarkably lower concentration of total EVs but a significantly higher percentage of LPS+ EVs. Interestingly, DIO faecal bEV<sup>LPS</sup> showed a higher abundance of <i>Proteobacteria</i> by 16S sequencing. Importantly, in DIO mice, a higher number of total EVs and bEV<sup>LPS</sup> consistently entered the hepatic portal vein and subsequently reached the liver, associated with increased expression of TLR4, macrophage markers (F4/80, CD86 and CD206), cytokines and receptors (<i>Il1rn</i>, <i>Ccr1</i>, <i>Cxcl10</i>, <i>Il2rg</i> and <i>Ccr2</i>). Furthermore, a portion of bEV<sup>LPS</sup> escaped liver and entered the peripheral circulation. In conclusion, bEV could be the key mediator orchestrating various well-established biological effects induced by gut bacteria on distant organs.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"13 7","pages":""},"PeriodicalIF":15.5,"publicationDate":"2024-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.12474","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141603713","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
Optimized AF4 combined with density cushion ultracentrifugation enables profiling of high-purity human blood extracellular vesicles 优化的 AF4 与密度垫超速离心法相结合,实现了对高纯度人血细胞外囊泡的分析。
IF 15.5 1区 医学
Journal of Extracellular Vesicles Pub Date : 2024-07-13 DOI: 10.1002/jev2.12470
Liqiao Hu, Xinyue Zheng, Maoge Zhou, Jifeng Wang, Lingjun Tong, Ming Dong, Tao Xu, Zonghong Li
{"title":"Optimized AF4 combined with density cushion ultracentrifugation enables profiling of high-purity human blood extracellular vesicles","authors":"Liqiao Hu,&nbsp;Xinyue Zheng,&nbsp;Maoge Zhou,&nbsp;Jifeng Wang,&nbsp;Lingjun Tong,&nbsp;Ming Dong,&nbsp;Tao Xu,&nbsp;Zonghong Li","doi":"10.1002/jev2.12470","DOIUrl":"10.1002/jev2.12470","url":null,"abstract":"<p>Extracellular vesicles (EVs) have emerged as a promising tool for clinical liquid biopsy. However, the identification of EVs derived from blood samples is hindered by the presence of abundant plasma proteins, which impairs the downstream biochemical analysis of EV-associated proteins and nucleic acids. Here, we employed optimized asymmetric flow field-flow fractionation (AF4) combined with density cushion ultracentrifugation (UC) to obtain high-purity and intact EVs with very low lipoprotein contamination from human plasma and serum. Further proteomic analysis revealed more than 1000 EV-associated proteins, a large proportion of which has not been previously reported. Specifically, we found that cell-line-derived EV markers are incompatible with the identification of plasma-EVs and proposed that the proteins MYCT1, TSPAN14, MPIG6B and MYADM, as well as the traditional EV markers CD63 and CD147, are plasma-EV markers. Benefiting from the high-purity of EVs, we conducted comprehensive miRNA profiling of plasma EVs and nanosized particles (NPs), as well as compared plasma- and serum-derived EVs, which provides a valuable resource for the EV research community. Overall, our findings provide a comprehensive assessment of human blood EVs as a basis for clinical biopsy applications.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"13 7","pages":""},"PeriodicalIF":15.5,"publicationDate":"2024-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.12470","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141603714","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
Cancer EV stimulate endothelial glycolysis to fuel protein synthesis via mTOR and AMPKα activation 癌细胞通过激活 mTOR 和 AMPKα 刺激内皮细胞糖酵解,为蛋白质合成提供燃料。
IF 15.5 1区 医学
Journal of Extracellular Vesicles Pub Date : 2024-07-13 DOI: 10.1002/jev2.12449
Joël E. J. Beaumont, Lydie M. O. Barbeau, Jinzhe Ju, Kim G. Savelkouls, Freek G. Bouwman, Marijke I. Zonneveld, Annelies Bronckaers, Kim R. Kampen, Tom G. H. Keulers, Kasper M. A. Rouschop
{"title":"Cancer EV stimulate endothelial glycolysis to fuel protein synthesis via mTOR and AMPKα activation","authors":"Joël E. J. Beaumont,&nbsp;Lydie M. O. Barbeau,&nbsp;Jinzhe Ju,&nbsp;Kim G. Savelkouls,&nbsp;Freek G. Bouwman,&nbsp;Marijke I. Zonneveld,&nbsp;Annelies Bronckaers,&nbsp;Kim R. Kampen,&nbsp;Tom G. H. Keulers,&nbsp;Kasper M. A. Rouschop","doi":"10.1002/jev2.12449","DOIUrl":"10.1002/jev2.12449","url":null,"abstract":"<p>Hypoxia is a common feature of solid tumours and activates adaptation mechanisms in cancer cells that induce therapy resistance and has profound effects on cellular metabolism. As such, hypoxia is an important contributor to cancer progression and is associated with a poor prognosis. Metabolic alterations in cells within the tumour microenvironment support tumour growth via, amongst others, the suppression of immune reactions and the induction of angiogenesis. Recently, extracellular vesicles (EV) have emerged as important mediators of intercellular communication in support of cancer progression. Previously, we demonstrated the pro-angiogenic properties of hypoxic cancer cell derived EV. In this study, we investigate how (hypoxic) cancer cell derived EV mediate their effects. We demonstrate that cancer derived EV regulate cellular metabolism and protein synthesis in acceptor cells through increased activation of mTOR and AMPKα. Using metabolic tracer experiments, we demonstrate that EV stimulate glucose uptake in endothelial cells to fuel amino acid synthesis and stimulate amino acid uptake to increase protein synthesis. Despite alterations in cargo, we show that the effect of cancer derived EV on recipient cells is primarily determined by the EV producing cancer cell type rather than its oxygenation status.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"13 7","pages":""},"PeriodicalIF":15.5,"publicationDate":"2024-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.12449","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141603712","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
Ceramide-mediated orchestration of oxidative stress response through filopodia-derived small extracellular vesicles 神经酰胺通过丝状体衍生的细胞外小泡介导氧化应激反应的协调。
IF 15.5 1区 医学
Journal of Extracellular Vesicles Pub Date : 2024-07-11 DOI: 10.1002/jev2.12477
Zainuddin Quadri, Ahmed Elsherbini, Simone M. Crivelli, Salim S. El-Amouri, Priyanka Tripathi, Zhihui Zhu, Xiaojia Ren, Liping Zhang, Stefka D. Spassieva, Mariana Nikolova-Karakashian, Erhard Bieberich
{"title":"Ceramide-mediated orchestration of oxidative stress response through filopodia-derived small extracellular vesicles","authors":"Zainuddin Quadri,&nbsp;Ahmed Elsherbini,&nbsp;Simone M. Crivelli,&nbsp;Salim S. El-Amouri,&nbsp;Priyanka Tripathi,&nbsp;Zhihui Zhu,&nbsp;Xiaojia Ren,&nbsp;Liping Zhang,&nbsp;Stefka D. Spassieva,&nbsp;Mariana Nikolova-Karakashian,&nbsp;Erhard Bieberich","doi":"10.1002/jev2.12477","DOIUrl":"10.1002/jev2.12477","url":null,"abstract":"<p>Extracellular vesicles (EVs) are shed from the plasma membrane, but the regulation and function of these EVs remain unclear. We found that oxidative stress induced by H<sub>2</sub>O<sub>2</sub> in Hela cells stimulated filopodia formation and the secretion of EVs. EVs were small (150 nm) and labeled for CD44, indicating that they were derived from filopodia. Filopodia-derived small EVs (sEVs) were enriched with the sphingolipid ceramide, consistent with increased ceramide in the plasma membrane of filopodia. Ceramide was colocalized with neutral sphingomyelinase 2 (nSMase2) and acid sphingomyelinase (ASM), two sphingomyelinases generating ceramide at the plasma membrane. Inhibition of nSMase2 and ASM prevented oxidative stress-induced sEV shedding but only nSMase2 inhibition prevented filopodia formation. nSMase2 was S-palmitoylated and interacted with ASM in filopodia to generate ceramide for sEV shedding. sEVs contained nSMase2 and ASM and decreased the level of these two enzymes in oxidatively stressed Hela cells. A novel metabolic labeling technique for EVs showed that oxidative stress induced secretion of fluorescent sEVs labeled with NBD-ceramide. NBD-ceramide-labeled sEVs transported ceramide to mitochondria, ultimately inducing cell death in a proportion of neuronal (N2a) cells. In conclusion, using Hela cells we provide evidence that oxidative stress induces interaction of nSMase2 and ASM at filopodia, which leads to shedding of ceramide-rich sEVs that target mitochondria and propagate cell death.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"13 7","pages":""},"PeriodicalIF":15.5,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.12477","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141579891","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
Connecting through ISEV's developing social media landscape 通过 ISEV 不断发展的社交媒体建立联系。
IF 15.5 1区 医学
Journal of Extracellular Vesicles Pub Date : 2024-07-08 DOI: 10.1002/jev2.12475
Tom. A. P. Driedonks, Deborah C. I. Goberdhan, Sujata Mohanty, Sarah Williams, Rienk Nieuwland, Kenneth W. Witwer, Ana Claudia Torrecilhas
{"title":"Connecting through ISEV's developing social media landscape","authors":"Tom. A. P. Driedonks,&nbsp;Deborah C. I. Goberdhan,&nbsp;Sujata Mohanty,&nbsp;Sarah Williams,&nbsp;Rienk Nieuwland,&nbsp;Kenneth W. Witwer,&nbsp;Ana Claudia Torrecilhas","doi":"10.1002/jev2.12475","DOIUrl":"10.1002/jev2.12475","url":null,"abstract":"<p>Social media are indispensable for organizations which communicate to a wide target audience. ISEV has been active on social media since it was founded in 2011. As we approach ISEV's 10-year anniversary on social media platform X, formerly known as Twitter, the members of ISEV's Communications Committee (2022-2024) evaluated how ISEV has used social media to convey the voice of the Society and its members, as well as looking to the future and how things may change and develop in the years to come.</p><p>We hope this editorial inspires you to “connect,” “like,” and “tweet” with us and other EV enthusiasts on social media.</p><p><b>Tom Driedonks</b>: Conceptualization (lead); data curation (lead); formal analysis (lead); investigation (lead); methodology (lead); project administration (lead); resources (equal); software (equal); supervision (lead); validation (equal); visualization (equal); writing—original draft (lead); writing—review and editing (lead). <b>Deborah Goberdhan</b>: Conceptualization (equal); formal analysis (equal); investigation (equal); methodology (equal); project administration (equal); resources (equal); validation (equal); visualization (equal); writing—original draft (equal); writing—review and editing (equal). <b>Sujata Mohanty</b>: Conceptualization (equal); data curation (equal); formal analysis (equal); investigation (equal); methodology (equal); resources (equal); software (equal); supervision (equal); validation (equal); visualization (equal); writing—original draft (equal); writing—review and editing (equal). <b>Sarah Williams</b>: Conceptualization (equal); data curation (equal); formal analysis (equal); investigation (equal); methodology (equal); resources (equal); software (equal); supervision (equal); validation (equal); visualization (equal); writing—original draft (equal); writing—review and editing (equal). <b>Rienk Nieuwland</b>: Data curation (equal); formal analysis (equal); investigation (equal); project administration (equal); resources (equal); software (equal); visualization (equal); writing—original draft (equal); writing—review and editing (equal). <b>Kenneth Witwer</b>: Data curation (equal); formal analysis (equal); investigation (equal); methodology (equal); resources (equal); validation (equal); visualization (equal); writing—original draft (equal); writing—review and editing (equal). <b>Ana Torrecilhas</b>: Conceptualization (lead); data curation (equal); formal analysis (equal); funding acquisition (lead); investigation (equal); methodology (equal); project administration (equal); resources (equal); software (equal); supervision (lead); validation (equal); visualization (equal); writing—original draft (lead); writing—review and editing (lead).</p><p>The authors declare no conflicts of interest.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"13 7","pages":""},"PeriodicalIF":15.5,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11231033/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141558883","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
Extracellular vesicle isolation and counting system (EVics) based on simultaneous tandem tangential flow filtration and large field-of-view light scattering 基于同步串联切向流过滤和大视场光散射的细胞外囊泡分离和计数系统(EVics)。
IF 15.5 1区 医学
Journal of Extracellular Vesicles Pub Date : 2024-07-08 DOI: 10.1002/jev2.12479
Ju-Hyun Bae, Chan-Hyeong Lee, Dokyung Jung, Kyungmoo Yea, Byoung-Joon Song, Hakho Lee, Moon-Chang Baek
{"title":"Extracellular vesicle isolation and counting system (EVics) based on simultaneous tandem tangential flow filtration and large field-of-view light scattering","authors":"Ju-Hyun Bae,&nbsp;Chan-Hyeong Lee,&nbsp;Dokyung Jung,&nbsp;Kyungmoo Yea,&nbsp;Byoung-Joon Song,&nbsp;Hakho Lee,&nbsp;Moon-Chang Baek","doi":"10.1002/jev2.12479","DOIUrl":"10.1002/jev2.12479","url":null,"abstract":"<p>Although the isolation and counting of small extracellular vesicles (sEVs) are essential steps in sEV research, an integrated method with scalability and efficiency has not been developed. Here, we present a scalable and ready-to-use extracellular vesicle (EV) isolation and counting system (EVics) that simultaneously allows isolation and counting in one system. This novel system consists of (i) EVi, a simultaneous tandem tangential flow filtration (TFF)-based EV isolation component by applying two different pore-size TFF filters, and (ii) EVc, an EV counting component using light scattering that captures a large field-of-view (FOV). EVi efficiently isolated 50–200 nm-size sEVs from 15 µL to 2 L samples, outperforming the current state-of-the-art devices in purity and speed. EVc with a large FOV efficiently counted isolated sEVs. EVics enabled early observations of sEV secretion in various cell lines and reduced the cost of evaluating the inhibitory effect of sEV inhibitors by 20-fold. Using EVics, sEVs concentrations and sEV PD-L1 were monitored in a 23-day cancer mouse model, and 160 clinical samples were prepared and successfully applied to diagnosis. These results demonstrate that EVics could become an innovative system for novel findings in basic and applied studies in sEV research.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"13 7","pages":""},"PeriodicalIF":15.5,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11231039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141558884","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
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