Extracellular vesicle最新文献

{"title":"Identification of robust and abundant reference transcripts for EV mRNA cargo normalization","authors":"Antje M. Zickler ,&nbsp;Radosław Grochowski ,&nbsp;André Görgens ,&nbsp;Erik Bäcklin ,&nbsp;Maximilian Kordes ,&nbsp;J.-Matthias Löhr ,&nbsp;Joel Z. Nordin ,&nbsp;Samir EL Andaloussi ,&nbsp;Daniel W. Hagey","doi":"10.1016/j.vesic.2025.100065","DOIUrl":"10.1016/j.vesic.2025.100065","url":null,"abstract":"<div><div>Extracellular vesicles (EVs) have been investigated intensively because of their potential as biomarkers of disease and their versatility as bioengineered therapeutic nanoparticles. EVs carry diverse biomolecular cargo, but absolute quantification has been challenging due to a lack of established molecular standards. Reliable identification of these has proven difficult owing to a scarcity of standardized global data sets spanning the heterogeneity of EV subtypes and cell sources. To identify reference messenger RNA (mRNA) transcripts, we analyze oligo-dT primed RNA-sequencing data from EVs originating from twelve different cell sources isolated using differential centrifugation followed by ultrafiltration. We identify 11 transcripts that are shared amongst the 50 most abundant in EVs from all of these cell sources. Following RT-PCR and deeper sequencing analysis, five transcripts warranted further investigation as molecular standards: TMSB4X, ACTB, GAPDH, VIM, and FTL. As such, we subjected the RT-qPCR results from two independent oligo-dT cDNA synthesis methods to stability assessment using the RefFinder analysis tool, conducted a proof-of-concept normalization on the levels of the variably expressed gene RAB13 and compared quantification of engineered mRNA loading with that of digital PCR. We confirmed the EV association of reference transcripts with EVs by performing gradient centrifugation followed by RT-qPCR and full-length mRNA analysis. To judge the applicability of these genes as reference transcripts for biomarker studies, we performed RNA-sequencing on EVs isolated from plasma by differential ultracentrifugation, and four other minimally processed biofluids. These findings confirm the applicability of these genes as molecular standards for EV-mRNA analysis and will aid in the standardization of EV research by establishing molecular reference genes that can be employed in diverse contexts.</div></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"5 ","pages":"Article 100065"},"PeriodicalIF":0.0,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143103004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vivo trafficking of cancer-derived exosomes and their role in metastasis","authors":"Shih-Yen Wei ,&nbsp;Sarah E. Shelton ,&nbsp;Ying-Chieh Chen ,&nbsp;Ke Huang","doi":"10.1016/j.vesic.2024.100063","DOIUrl":"10.1016/j.vesic.2024.100063","url":null,"abstract":"<div><div>Cancer metastasis is one of the leading causes of cancer-related mortality. This process is driven by a combination of biological processes including invasion, intravasation, circulation, extravasation, and colonization of distant organs, among which cancer cell-derived exosomes facilitate metastasis through their enriched oncogenic miRNAs and lncRNAs to enhance cancer cell migration and invasion, promote epithelial-mesenchymal transition in recipient cells, help cancer cells evade immune detection, and alter the microenvironment to promote the formation of a pre-metastatic niche. While the role of cancer exosomes in various metastatic processes has been extensively studied, the exosomal trafficking of cancer cell-derived exosomes has not been thoroughly reviewed. This review describes the dynamics between cancer cell-derived exosomes and various cellular components in blood and lymph circulation during cancer metastasis. Additionally, we emphasize the role of cancer exosomes in establishing pre-metastatic niches and in promoting metastasis to secondary sites. By offering a thorough review of exosome trafficking in cancer metastasis, this review may potentially help the future identification of treatment targets for metastasis inhibition.</div></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"5 ","pages":"Article 100063"},"PeriodicalIF":0.0,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143103005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Packaging of humanized anti-HER2 monoclonal antibody into small extracellular vesicles","authors":"Junxin Mai ,&nbsp;Yuanmei Zhang ,&nbsp;Zhixuan Liang ,&nbsp;Wei Xu ,&nbsp;Qian Shao ,&nbsp;Jingwen Peng ,&nbsp;Jing Chen ,&nbsp;Yuting Shentu ,&nbsp;Zixin Chen ,&nbsp;Juling Ji ,&nbsp;Yuhua Ji ,&nbsp;Qiuling Xie","doi":"10.1016/j.vesic.2024.100064","DOIUrl":"10.1016/j.vesic.2024.100064","url":null,"abstract":"<div><div>Small extracellular vesicles (sEVs), including exosomes and microvesicles (MVs), are nano-sized membranous particles shed by almost all cell types. Both play significant roles in cellular communication by transferring proteins, nucleic acids, lipids, and metabolites to recipient cells and impact a broad range of pathophysiological processes, whereby they hold great promise in clinical application as therapeutic cargo carriers. Previous studies have shown that the membrane antibodies on exosomes derived from primary B cells, B cell lines, and hybridoma can present antigen-induced T cell responses. However, whether secretory antibodies can be released by sEVs and play a biological role has been unclear. Antibody against human epidermal growth factor receptor-2 (HER2 antibody) is a humanized monoclonal IgG antibody. In this study, by using a CHO cell line expressing recombinant anti-HER2 monoclonal antibody (CHO-HER2), we demonstrated the packaging of the intact HER2 antibodies in the sEVs (sEVs-HER2), and the involvement of endocytosis in their anti-proliferation effects on the BT474 cells, a HER2-overexpressing cell line. Further unbiased proteomic analysis showed that the heavy and light chains of IgG were the most abundant sEVs proteins and revealed that besides endosomal and lysosomes proteins, the proteins involved in the Golgi apparatus were significantly enriched in sEVs-HER2. Brefeldin A (BFA), a potent inhibitor of protein trafficking from the endoplasmic reticulum (ER) to the Golgi apparatus, significantly suppressed the titer of anti-HER2 antibody in both supernatant and sEVs-HER2. Moreover, the HER2 antibodies in the sEVs could be significantly suppressed by Tipifarnib and Y27632, inhibitors targeting exosomes and MV biogenesis/release, respectively. This study demonstrated that the secretory HER2 antibody could be packaged into sEVs and maintain its anti-proliferation activity. Moreover, this study suggested that the HER2 antibodies could be packaged in both exosomes and MVs and the involvement of the Golgi pathway.</div></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"5 ","pages":"Article 100064"},"PeriodicalIF":0.0,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143103006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mapping growth and trajectory in the field of extracellular vesicles: A scientometric analysis","authors":"Liam Hourigan ,&nbsp;William Phillips ,&nbsp;Amirmohammad Nasiri Kenari ,&nbsp;Krishna Chaitanya Pavani ,&nbsp;Chaomei Chen ,&nbsp;An Hendrix ,&nbsp;Lesley Cheng ,&nbsp;Andrew F. Hill","doi":"10.1016/j.vesic.2024.100062","DOIUrl":"10.1016/j.vesic.2024.100062","url":null,"abstract":"<div><div>Extracellular vesicles (EVs) are a diverse population of membrane bound particles released by cells. They play roles in a variety of diseases and biological functions, piquing the interest of researchers and industry alike. The field is often described as undergoing ‘explosive growth’, however this growth has not been characterized in depth. Scientometrics is a quantitative approach for analyzing scientific works, allowing for a broadly focused review of the EV field. Drawing on 52210 publications from the Web of Science, this review charts the field's using the programs CiteSpace and Bibliometrix. These analyses are further enriched with data from the Dimensions database along with data from EV-TRACK, an EV-specific data source. We thoroughly describe the field's various subdomains, identifying their different lines of inquiry, their variable use of nomenclature and their progression along the translational pipeline. Cancer features prominently alongside other diseases and conditions, with the majority of research having a basic aetiological focus. These subdomains are compared against a global map of science, revealing a stable and substantial EV research community revolving around the International Society for Extracellular Vesicles ISEV and the ‘MISEV paradigm’. A shared framework of knowledge and communication, grounded in the field's history and guiding its future.</div></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"5 ","pages":"Article 100062"},"PeriodicalIF":0.0,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143103007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic potential of extracellular vesicles in inflammatory diseases","authors":"Xiaojian Huang ,&nbsp;Shen Zhang ,&nbsp;Zhenzhen Wang","doi":"10.1016/j.vesic.2024.100058","DOIUrl":"10.1016/j.vesic.2024.100058","url":null,"abstract":"<div><div>Extracellular vesicles are spherical lipid bilayer vesicles composed of lipids, proteins and nucleic acids that could deliver signaling molecules into target cells to regulate their function and biological processes. Recently, increasing numbers of studies have demonstrated the therapeutic potential of extracellular vesicles (EVs) in inflammatory diseases by migrating the inflammatory responses and ameliorating physiological deteriorations, as well as promoting angiogenesis and mediating immune responses. In this review, we mainly focused on the biological and molecular functions of EVs in anti-inflammatory activity and their protective roles in many kinds of inflammation diseases, including pneumonia, neuroinflammatory diseases, inflammatory bowel disease, osteoarthritis, rheumatoid arthritis, cardiovascular disease, dry eye disease, periodontitis, diabetic wounds and systemic lupus erythematosus. Furthermore, we further summarized the underlying therapeutic mechanisms of EVs in inflammatory diseases and discussed the current challenges and future perspectives of EVs in clinical applications, providing an insight into the potential of EVs as therapeutic agent for other diseases.</div></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"5 ","pages":"Article 100058"},"PeriodicalIF":0.0,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143103008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Visualization strategies of extracellular vesicles: Illuminating the invisible ‘dust’ in theranostics","authors":"Kaiyue Zhang ,&nbsp;Jingxuan Hu ,&nbsp;Yilan Hu","doi":"10.1016/j.vesic.2024.100061","DOIUrl":"10.1016/j.vesic.2024.100061","url":null,"abstract":"<div><div>Extracellular vesicles (EVs), lipid bilayer vesicles with diameters of 30-150 nm derived from nearly all cell types, were once dismissed as “platelet dust” but are now recognized as key mediators of intercellular communication, playing vital roles in both physiological and pathophysiological processes. However, the clinical applications of EVs in theranostics remain limited by the challenge of effectively visualizing them at high resolution both <em>in vitro</em> and <em>in vivo</em>, primarily due to their nanoscale size. To address this limitation, researchers worldwide are developing innovative methods for labeling and visualizing EVs, aiming to unlock their full potential in optimized theranostic applications. This review provides a comprehensive overview of current strategies for EV labeling across various experimental settings and highlights their promising theranostic applications of diverse diseases.</div></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"4 ","pages":"Article 100061"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143097288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prospects and challenges of targeted extracellular vesicles drug delivery for cancer treatment","authors":"Fatemeh Maher ,&nbsp;Ali Samadi ,&nbsp;Peyman Asadi ,&nbsp;Isabella Jodoin","doi":"10.1016/j.vesic.2024.100059","DOIUrl":"10.1016/j.vesic.2024.100059","url":null,"abstract":"<div><div>Extracellular vesicles (EVs) have the ability to alter the phenotypes and functions of other cells as well as reflect the state of the cell from whence they originated.</div><div>Extracellular vesicles, or EVs, are membrane-bound nanostructures released into the extracellular environment. Under both normal and pathological circumstances, they are widely discharged from cells and display a variety of sizes, contents, and surface marks. These EVs are abundant in human serum, yet it might be difficult to separate them from non-EV lipid particles and serum proteins. These vesicles influence several physiological and pathological processes, including those that occur in the tumor microenvironment (TME), by transporting different cellular constituents such as proteins, mRNAs, miRNAs, DNA, and lipids across distances. EVs are potential possibilities for therapeutic agents, medication delivery methods, and disease biomarkers due to their crucial functions in cellular communication. EV detection has the potential to serve as a diagnostic biomarker and can facilitate early identification, particularly in the context of cancer diagnosis. Furthermore, EV subtypes may be clinically significant as different subtypes are emerging as targeted medication delivery methods. There is still a need for non-invasive biomarkers to track biological processes for treatment and diagnosis. In the future, utilizing EVs' distinct composition may open up new possibilities for enhanced diagnosis and treatment.</div></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"4 ","pages":"Article 100059"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143096973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From isolation to detection, advancing insights into endothelial matrix-bound vesicles","authors":"Sahimy Ayus-Martinez ,&nbsp;William Meza-Morales ,&nbsp;Jesus Jimenez-Osorio ,&nbsp;Maria Buendia-Otero ,&nbsp;Luis López ,&nbsp;Lisandro Cunci ,&nbsp;Donald O. Freytes ,&nbsp;Camilo Mora","doi":"10.1016/j.vesic.2024.100060","DOIUrl":"10.1016/j.vesic.2024.100060","url":null,"abstract":"<div><div>Matrix-bound vesicles (MBVs), an integral part of the extracellular matrix (ECM), are emerging as pivotal factors in ECM-driven molecular signaling. This study is the first to report the isolation of MBVs from porcine arterial endothelial cell basement membranes (A-MBVs) and thyroid cartilage (C-MBVs), the latter serving as a negative control due to its minimal vascular characteristics. Using Transmission Electron Microscopy (TEM), Nano-Tracking Analysis (NTA), Electrochemical Impedance Spectroscopy (EIS), and Atomic Force Microscopy (AFM), we orthogonally characterized the isolated MBVs. We detected the presence and preservation of vascular endothelial cadherin (CD144) in A-MBVs, its low to non-detetcted in C-MBVs, in which SOX9, a chondrocyte marker, was detected. Moreover, we developed a prototype of an immuno-functionalized screen-printed electrode designed for the immunoadsorption of CD144+ MBVs. This device facilitated the electrochemical detection of the targeted vesicles and allowed for their subsequent topological characterization using AFM, which verified the integrity and morphology of CD144+ MBVs post-immunoadsorption. These advancements enhance our comprehension of MBVs as conveyors of tissue-specific signals and pioneer new avenues for harnessing their cargo in biomedical applications. This research sets a significant precedent for future studies on the application of MBVs in regenerative medicine and ECM signaling.</div></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"4 ","pages":"Article 100060"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11759483/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143048614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel administration strategies for tissue-specific delivery of extracellular vesicles","authors":"Junyao Deng ,&nbsp;Qishan Li ,&nbsp;Fei Wang","doi":"10.1016/j.vesic.2024.100057","DOIUrl":"10.1016/j.vesic.2024.100057","url":null,"abstract":"<div><div>Extracellular vesicles (EVs) are nanoparticles released by cells with bilayer lipid membranes that have been demonstrated to regulate biological activities. The potential of EVs as a novel therapeutic or drug delivery platform has already been identified in emerging research. The therapeutic efficacy of EVs is contingent upon the quantity of EVs internalized by target cells, which necessitates the enhanced retention of EVs in target organs. Accordingly, various novel administration strategies for the targeted delivery of therapeutic EVs into specific tissues were developed. This review presents a comprehensive overview of the latest developments in EV delivery routes for brain-, heart-, lung-, skin-, eye-, and gastrointestinal tract-specific applications. We believe that the emergence of innovative EV administration strategies will contribute to the future clinical trials and eventual applicability of EV-based therapeutics.</div></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"4 ","pages":"Article 100057"},"PeriodicalIF":0.0,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142720069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of plasma-derived small extracellular vesicle miRNA and protein cargo in hereditary angioedema","authors":"Linda Hofmann ,&nbsp;Robin Lochbaum ,&nbsp;Lutz Schütt ,&nbsp;Ralph Röth ,&nbsp;Stefanie Schmitteckert ,&nbsp;Barbara Wollenberg ,&nbsp;Thomas K. Hoffmann ,&nbsp;Cornelia Brunner ,&nbsp;Jens Greve ,&nbsp;Janina Hahn ,&nbsp;Marie-Nicole Theodoraki","doi":"10.1016/j.vesic.2024.100056","DOIUrl":"10.1016/j.vesic.2024.100056","url":null,"abstract":"<div><div>Hereditary angioedema (HAE) is an inherited disorder causing attacks of subcutaneous tissue or mucosa swelling. The disease burden and attack frequencies vary significantly among patients. This is the first pilot study investigating small extracellular vesicles (sEV) as potential disease modulators in HAE.</div><div>Plasma-derived sEVs from HAE patients and healthy donors (HD) were thoroughly characterized by Western blot, transmission electron microscopy, nanoparticle tracking and bead-based flow cytometry. The miRNA content of sEVs was examined by nCounter technology and used to predict sEV-based pathomechanisms <em>in silico</em>. All sEV readouts were analyzed regarding HAE-related changes and associations with clinical parameters and attack frequency.</div><div>Total sEV protein levels were elevated in HAE patients compared to HD. In HAE patients, lower levels of sEVs carrying CD8, CD209, CD81, CD24 and CD44 were measured. sEV miRNA profiling revealed 84 HAE-exclusive and 30 significantly HAE-upregulated candidates. Core hubs of their predicted interaction networks were AGO2, VEGF, RGS5, MTA1, IFG1 and BAX. A set of 12 and 36 sEV miRNAs were restricted to patients with absent attacks or patients with present attacks during prophylactic therapy, respectively.</div><div>sEVs, especially sEV miRNAs, could contribute to disease pathogenesis and differential attack frequencies. They emerged as disease modulators in HAE and require further study to reveal underlying mechanisms.</div></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"4 ","pages":"Article 100056"},"PeriodicalIF":0.0,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142657127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}