Journal of extracellular biology最新文献

{"title":"Food-derived extracellular vesicles in the human gastrointestinal tract: Opportunities for personalised nutrition and targeted therapeutics","authors":"Natalie P. Turner","doi":"10.1002/jex2.154","DOIUrl":"https://doi.org/10.1002/jex2.154","url":null,"abstract":"<p>Food-derived extracellular vesicles (FDEVs) such as those found in mammalian milk and plants are of great interest for both their health benefits and ability to act as biological nanocarriers. While the extracellular vesicle (EV) field is expanding rapidly to perform characterisation studies on FDEVs from plants, yeasts and bacteria, species-specific differences in EV uptake and function in the human gastrointestinal (GI) tract are poorly understood. Moreover, the effects of food processing on the EV surfaceome and intraluminal content also raises questions surrounding biological viability once consumed. Here, I present a case for increasing community-wide focus on understanding the cellular uptake of FDEVs from different animal, plant, yeast, and bacterial species and how this may impact their function in the human, which will have implications for human health and therapeutic strategies alike.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"3 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jex2.154","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140820718","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":"Microvesicles derived from dermal myofibroblasts modify the integrity of the blood and lymphatic barriers using distinct endocytosis pathways","authors":"Syrine Arif,&nbsp;Megan Richer,&nbsp;Sébastien Larochelle,&nbsp;Véronique J. Moulin","doi":"10.1002/jex2.151","DOIUrl":"https://doi.org/10.1002/jex2.151","url":null,"abstract":"<p>Microvesicles (MVs) are a subtype of extracellular vesicles that can transfer biological information from their producer cells to target cells. This communication can in turn affect both normal and pathological processes. Mounting evidence has revealed that dermal wound myofibroblasts (Wmyo) produce MVs, which can transfer biomolecules impacting receptor cells such as human dermal microvascular endothelial cells (HDMECs). While the effects of MVs on HDMECs are generally well described in the literature, little is known about the transport of MVs across the HDMEC barrier, and their potential effect on the barrier integrity remains unknown. Here, we investigated these roles of Wmyo-derived MVs on two sub-populations of HDMECs, blood endothelial cells (BECs) and lymphatic endothelial cells (LECs). Using an in vitro model to mimic the endothelial barrier, we showed that MVs crossed the LEC barrier but not the BEC barrier. In addition, we demonstrated that MVs were able to influence the cell-cell junctions of HDMECs. Specifically, we observed that after internalization via the predominantly caveolin-dependent pathway, MVs induced the opening of junctions in BECs. Conversely, in LECs, MVs mainly use the macropinocytosis pathway and induce closure of these junctions. Moreover, proteins in the MV membrane were responsible for this effect, but not specifically those belonging to the VEGF family. Finally, we found that once the LEC barrier permeability was reduced by MV stimuli, MVs ceased to cross the barrier. Conversely, when the BEC barrier was rendered permeable following stimulation with MVs, they were subsequently able to cross the barrier via the paracellular pathway. Taken together, these results suggest that the study of Wmyo-derived MVs offers valuable insights into their interaction with the HDMEC barrier in the context of wound healing. They highlight the potential significance of these MVs in the overall process.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"3 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jex2.151","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140820719","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":"Comparative analysis of the effects of different purification methods on the yield and purity of cow milk extracellular vesicles","authors":"Santeri Kankaanpää,&nbsp;Markus Nurmi,&nbsp;Markus Lampimäki,&nbsp;Heidi Leskinen,&nbsp;Anni Nieminen,&nbsp;Anatoliy Samoylenko,&nbsp;Seppo J. Vainio,&nbsp;Sari Mäkinen,&nbsp;Lauri Ahonen,&nbsp;Juha Kangasluoma,&nbsp;Tuukka Petäjä,&nbsp;Sirja Viitala","doi":"10.1002/jex2.149","DOIUrl":"https://doi.org/10.1002/jex2.149","url":null,"abstract":"<p>Isolation of extracellular vesicles (EV) has been developing rapidly in parallel with the interest in EVs. However, commonly utilized protocols may not suit more challenging sample matrixes and could potentially yield suboptimal results. Knowing and assessing the pitfalls of isolation procedure to be used, should be involved to some extent for EV analytics. EVs in cow milk are of great interest due to their abundancy and large-scale availability as well as their cross-species bioavailability and possible use as drug carriers. However, the characteristics of milk EVs overlap with those of other milk components. This makes it difficult to isolate and study EVs individually. There exists also a lack of consensus for isolation methods. In this study, we demonstrated the differences between various differential centrifugation-based approaches for isolation of large quantities of EVs from cow milk. Samples were further purified with gradient centrifugation and size exclusion chromatography (SEC) and differences were analyzed. Quality measurements were conducted on multiple independent platforms. Particle analysis, electron microscopy and RNA analysis were used, to comprehensively characterize the isolated samples and to identify the limitations and possible sources of contamination in the EV isolation protocols. Vesicle concentration to protein ratio and RNA to protein ratios were observed to increase as samples were purified, suggesting co-isolation with major milk proteins in direct differential centrifugation protocols. We demonstrated a novel size assessment of vesicles using a particle mobility analyzer that matched the sizing using electron microscopy in contrast to commonly utilized nanoparticle tracking analysis. Based on the standards of the International Society for Extracellular Vesicles and the quick checklist of EV-Track.org for EV isolation, we emphasize the need for complete characterization and validation of the isolation protocol with all EV-related work to ensure the accuracy of results and allow further analytics and experiments.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"3 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jex2.149","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140632004","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":"Oxidative stress-induced changes in the transcriptomic profile of extracellular vesicles","authors":"Elizabeth R. Dellar,&nbsp;Claire Hill,&nbsp;David R. F. Carter,&nbsp;Luis Alberto Baena-Lopez","doi":"10.1002/jex2.150","DOIUrl":"https://doi.org/10.1002/jex2.150","url":null,"abstract":"<p>Extracellular vesicles (EVs) have been proposed to play dual roles in cellular homeostasis, functioning both to remove unwanted intracellular molecules, and to enable communication between cells as a means of modulating cellular responses in different physiological and pathological scenarios. EVs contain a broad range of cargoes, including multiple biotypes of RNA, which can vary depending on the cell status, and may function as signalling molecules. In this study, we carried out comparative transcriptomic analysis of <i>Drosophila</i> EVs and cells, demonstrating that the RNA profile of EVs is distinct from cells and shows dose-dependent changes in response to oxidative stress. We identified a high abundance of snoRNAs in EVs, alongside an enrichment of intronic and untranslated regions (UTRs) of mRNAs under stress. We also observed an increase in the relative abundance of either aberrant or modified mRNAs under stress. These findings suggest that EVs may function both for the elimination of specific cellular RNAs, and for the incorporation of RNAs that may hold signalling potential.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"3 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jex2.150","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140631978","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":"Extracellular vesicles and endothelial dysfunction in infectious diseases","authors":"Linfang Zhang,&nbsp;Jingshu Chi,&nbsp;Hao Wu,&nbsp;Xiujuan Xia,&nbsp;Canxia Xu,&nbsp;Hong Hao,&nbsp;Zhenguo Liu","doi":"10.1002/jex2.148","DOIUrl":"https://doi.org/10.1002/jex2.148","url":null,"abstract":"<p>Cardiovascular diseases (CVDs) remain the leading cause of mortality and morbidity globally. Studies have shown that infections especially bacteraemia and sepsis are associated with increased risks for endothelial dysfunction and related CVDs including atherosclerosis. Extracellular vesicles (EVs) are small, sealed membrane-derived structures that are released into body fluids and blood from cells and/or microbes and are critically involved in a variety of important cell functions and disease development, including intercellular communications, immune responses and inflammation. It is known that EVs-mediated mechanism(s) is important in the development of endothelial dysfunction in infections with a diverse spectrum of microorganisms including <i>Escherichia coli</i>, <i>Candida albicans</i>, SARS-CoV-2 (the virus for COVID-19) and <i>Helicobacter pylori</i>. <i>H. pylori</i> infection is one of the most common infections globally. During <i>H. pylori</i> infection, EVs can carry <i>H. pylori</i> components, such as lipopolysaccharide, cytotoxin-associated gene A, or vacuolating cytotoxin A, and transfer these substances into endothelial cells, triggering inflammatory responses and endothelial dysfunction. This review is to illustrate the important role of EVs in the pathogenesis of infectious diseases, and the development of endothelial dysfunction in infectious diseases especially <i>H. pylori</i> infection, and to discuss the potential mechanisms and clinical implications.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"3 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jex2.148","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140550129","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":"Characterising the HLA-I immunopeptidome of plasma-derived extracellular vesicles in patients with melanoma","authors":"Caitlin Boyne,&nbsp;Abigail Coote,&nbsp;Silvia Synowsky,&nbsp;Aaron Naden,&nbsp;Sally Shirran,&nbsp;Simon J. Powis","doi":"10.1002/jex2.146","DOIUrl":"https://doi.org/10.1002/jex2.146","url":null,"abstract":"<p>Extracellular vesicles (EVs) frequently express human leukocyte antigen class I (HLA-I) molecules. The immunopeptidomes presented on EV HLA-I are being mapped to provide key information on both specific cancer-related peptides, and for larger immunopeptidomic signatures associated with disease. Utilizing HLA-I immunoisolation and mass spectrometry, we characterised the HLA-I immunopeptidome of EVs derived from the melanoma cancer cell line, ESTDAB-026, and the plasma of 12 patients diagnosed with advanced stage melanoma, alongside 11 healthy controls. The EV HLA-I immunopeptidome derived from melanoma cells features T cell epitopes with known immunogenicity and peptides derived from known tumour associated antigens (TAAs). Both T cell epitopes with known immunogenicity and peptides derived from known TAAs were also identifiable in the melanoma patient samples. Patient stratification into two distinct groups with varying immunological profiles was also observed. The data obtained in this study suggests for the first time that the HLA-I immunopeptidome of EVs derived from blood may aid in the detection of important diagnostic or prognostic biomarkers and also provide new immunotherapy targets.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"3 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jex2.146","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140291378","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":"Multimode chromatography-based techniques for high purity isolation of extracellular vesicles from human blood plasma","authors":"Alan J. Zimmerman,&nbsp;Getulio Pereira de Oliveira Jr.,&nbsp;Xianyi Su,&nbsp;Jacqueline Wood,&nbsp;Zhengxin Fu,&nbsp;Brandy Pinckney,&nbsp;John Tigges,&nbsp;Ionita Ghiran,&nbsp;Alexander R. Ivanov","doi":"10.1002/jex2.147","DOIUrl":"https://doi.org/10.1002/jex2.147","url":null,"abstract":"<p>Extracellular vesicles (EVs) play a pivotal role in various biological pathways, such as immune responses and the progression of diseases, including cancer. However, it is challenging to isolate EVs at high purity from blood plasma and other biofluids due to their low abundance compared to more predominant biomolecular species such as lipoprotein particles and free protein complexes. Ultracentrifugation-based EV isolation, the current gold standard technique, cannot overcome this challenge due to the similar biophysical characteristics of such species. We developed several novel approaches to enrich EVs from plasma while depleting contaminating molecular species using multimode chromatography-based strategies. On average, we identified 716 ± 68 and 1054 ± 35 protein groups in EV isolates from 100 µL of plasma using multimode chromatography- and ultracentrifugation-based techniques, respectively. The developed methods resulted in similar EV isolates purity, providing significant advantages in simplicity, throughput, scalability, and applicability for various downstream analytical and potential clinical applications.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"3 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jex2.147","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140181644","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":"ELISA-based detection of immunoglobulins against extracellular vesicles in blood plasma","authors":"Tom A. P. Driedonks,&nbsp;Linglei Jiang,&nbsp;Olesia Gololobova,&nbsp;Zhaohao Liao,&nbsp;Kenneth W. Witwer","doi":"10.1002/jex2.129","DOIUrl":"https://doi.org/10.1002/jex2.129","url":null,"abstract":"<p>Extracellular vesicles (EVs) are intensively investigated for their therapeutic potential and application as drug delivery vehicle. A broad perception of favourable safety profiles and low immunogenicity make EVs an attractive alternative to synthetic nanoparticles. We recently showed that repeated intravenous administration of human cell-derived EVs into pig-tailed macaques unexpectedly elicited antibody responses after three or more injections. This coincided with decreasing EV circulation time, and may thus hamper successful EV-mediated cargo delivery into tissues. Here, we share the custom ELISA protocol that we used to measure such antibody responses. This protocol may help other researchers evaluate immune responses to EV-based therapies in preclinical studies.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"3 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jex2.129","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140053092","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":"Dysregulation of intercellular communication in vitro and in vivo via extracellular vesicles secreted by pancreatic duct adenocarcinoma cells and generated under the influence of the AG9 elastin peptide-conditioned microenvironment","authors":"Lise Nannan,&nbsp;Salomé Decombis,&nbsp;Christine Terryn,&nbsp;Sandra Audonnet,&nbsp;Jean Michel,&nbsp;Sylvie Brassart-Pasco,&nbsp;Willy Gsell,&nbsp;Uwe Himmelreich,&nbsp;Bertrand Brassart","doi":"10.1002/jex2.145","DOIUrl":"https://doi.org/10.1002/jex2.145","url":null,"abstract":"<p>Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with poor prognosis due to its highly metastatic profile. Intercellular communication between cancer and stromal cells via extracellular vesicles (EVs) is crucial for the premetastatic microenvironment preparation leading to tumour metastasis. This study shows that under the influence of bioactive peptides derived from the extracellular matrix microenvironment, illustrated here by the AG-9 elastin-derived peptide (EDP), PDAC cells secrete more tumour-derived EVs. Compared to PDAC-derived EVs, tumour-derived EVs resulting from AG-9 treatment (PDAC AG-9-derived EVs) significantly stimulated cell proliferation. At constant amount, tumour-derived EVs were similarly taken up by PDAC and HMEC-1 cells. Tumour-derived EVs stimulated cell proliferation, migration, proteinase secretion, and angiogenesis. Bioluminescence imaging allowed tumour-derived EV/FLuc+ tracking in vivo in a PDAC mouse model. The biodistribution of PDAC AG-9-derived EVs was different to PDAC-derived EVs. Our results demonstrate that the microenvironment, through EDP release, may not only influence the genesis of EVs but may also affect tumour progression (tumour growth and angiogenesis), and metastatic homing by modifying the in vivo biodistribution of tumour-derived EVs. They are potential candidates for targeted drug delivery and modulation of tumour progression, and they constitute a new generation of therapeutic tools, merging oncology and genic therapy.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"3 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jex2.145","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140053091","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":"Profile of matrix-entrapped extracellular vesicles of microenvironmental and infiltrating cell origin in decellularized colorectal cancer and adjacent mucosa","authors":"Sarah Tassinari,&nbsp;Edoardo D'Angelo,&nbsp;Federico Caicci,&nbsp;Cristina Grange,&nbsp;Jacopo Burrello,&nbsp;Matteo Fassan,&nbsp;Alessia Brossa,&nbsp;Riccardo Quoc Bao,&nbsp;Gaya Spolverato,&nbsp;Marco Agostini,&nbsp;Federica Collino,&nbsp;Benedetta Bussolati","doi":"10.1002/jex2.144","DOIUrl":"https://doi.org/10.1002/jex2.144","url":null,"abstract":"<p>Cellular elements that infiltrate and surround tumours and pre-metastatic tissues have a prominent role in tumour invasion and growth. The extracellular vesicles specifically entrapped and stored within the extracellular matrix (ECM-EVs) may reflect the different populations of the tumour microenvironment and their change during tumour progression. However, their profile is at present unknown. To elucidate this aspect, we isolated and characterized EVs from decellularized surgical specimens of colorectal cancer and adjacent colon mucosa and analyzed their surface marker profile. ECM-EVs in tumours and surrounding mucosa mainly expressed markers of lymphocytes, natural killer cells, antigen-presenting cells, and platelets, as well as epithelial cells, representing a multicellular microenvironment. No difference in surface marker expression was observed between tumour and mucosa ECM-EVs in stage II-III tumours. At variance, in the colon mucosa adjacent to stage IV carcinomas, ECM-EV profile showed a significantly increased level of immune, epithelial and platelet markers in comparison to the matrix of the corresponding tumour. The increase of EVs from immune cells and platelets was not observed in the mucosa adjacent to low-stage tumours. In addition, CD25, a T-lymphocyte marker, resulted specifically overexpressed by ECM-EVs from stage IV carcinomas, possibly correlated with the pro-tolerogenic environment found in the corresponding tumour tissue. These results outline the tissue microenvironmental profile of EVs in colorectal carcinoma-derived ECM and unveil a profound change in the healthy mucosa adjacent to high-stage tumours.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"3 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jex2.144","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139976543","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}