Journal of Extracellular Vesicles最新文献

{"title":"A multiantigenic antibacterial nanovaccine utilizing hybrid membrane vesicles for combating Pseudomonas aeruginosa infections","authors":"Xinran Peng,&nbsp;Yuanjing Luo,&nbsp;Li Yang,&nbsp;Yi Yan Yang,&nbsp;Peiyan Yuan,&nbsp;Xinhai Chen,&nbsp;Guo-Bao Tian,&nbsp;Xin Ding","doi":"10.1002/jev2.12524","DOIUrl":"https://doi.org/10.1002/jev2.12524","url":null,"abstract":"<p>Bacterial infections, especially those caused by multidrug-resistant pathogens, pose a significant threat to public health. Vaccines are a crucial tool in fighting these infections; however, no clinically available vaccine exists for the most common bacterial infections, such as those caused by <i>Pseudomonas aeruginosa</i>. Herein, a multiantigenic antibacterial nanovaccine (AuNP@HMV@SPs) is reported to combat <i>P. aeruginosa</i> infections. This nanovaccine utilizes the hybrid membrane vesicles (HMVs) created by fusing macrophage membrane vesicles (MMVs) with bacterial outer membrane vesicles (OMVs). The HMVs mitigate the toxic effects of both OMVs and bacterial secreted toxins (SP) adsorbed on the surface of MMVs, while preserving their stimulating properties. Gold nanoparticles (AuNPs) are utilized as adjuvant to enhance immune response without comprising safety. The nanovaccine AuNP@HMV@SPs induces robust humoral and cellular immune responses, leading to destruction of bacterial cells and neutralization of their secreted toxins. In murine models of septicemia and pneumonia caused by <i>P. aeruginosa</i>, AuNP@HMV@SPs exhibits superior prophylactic efficacy compared to control groups including OMVs, or MMVs@SPs and HMV@SPs, achieving 100% survival in septicemia and &gt; 99.9% reduction in lung bacterial load in pneumonia. This study highlights AuNP@HMV@SPs as a safe and effective antibacterial nanovaccine, targeting both bacteria and their secreted toxins, and offers a promising platform for developing multiantigenic antibacterial vaccines against multidrug-resistant pathogens.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":null,"pages":null},"PeriodicalIF":15.5,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.12524","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142435596","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":"Snorkel-tag based affinity chromatography for recombinant extracellular vesicle purification","authors":"Madhusudhan Reddy Bobbili,&nbsp;André Görgens,&nbsp;Yan Yan,&nbsp;Stefan Vogt,&nbsp;Dhanu Gupta,&nbsp;Giulia Corso,&nbsp;Samir Barbaria,&nbsp;Carolina Patrioli,&nbsp;Sylvia Weilner,&nbsp;Marianne Pultar,&nbsp;Jaroslaw Jacak,&nbsp;Matthias Hackl,&nbsp;Markus Schosserer,&nbsp;Regina Grillari,&nbsp;Jørgen Kjems,&nbsp;Samir EL Andaloussi,&nbsp;Johannes Grillari","doi":"10.1002/jev2.12523","DOIUrl":"https://doi.org/10.1002/jev2.12523","url":null,"abstract":"<p>Extracellular vesicles (EVs) are lipid nanoparticles and play an important role in cell-cell communications, making them potential therapeutic agents and allowing to engineer for targeted drug delivery. The expanding applications of EVs in next generation medicine is still limited by existing tools for scaling standardized EV production, single EV tracing and analytics, and thus provide only a snapshot of tissue-specific EV cargo information. Here, we present the Snorkel-tag, for which we have genetically fused the EV surface marker protein CD81, to a series of tags with an additional transmembrane domain to be displayed on the EV surface, resembling a snorkel. This system enables the affinity purification of EVs from complex matrices in a non-destructive form while maintaining EV characteristics in terms of surface protein profiles, associated miRNA patterns and uptake into a model cell line. Therefore, we consider the Snorkel-tag to be a widely applicable tool in EV research, allowing for efficient preparation of EV standards and reference materials, or dissecting EVs with different surface markers when fusing to other tetraspanins in vitro or in vivo.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":null,"pages":null},"PeriodicalIF":15.5,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.12523","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142435595","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":"HTLV-1 infected T cells cause bone loss via small extracellular vesicles","authors":"Nitin Kumar Pokhrel,&nbsp;Amanda R. Panfil,&nbsp;Haniya Habib,&nbsp;Shamreethaa Seeniraj,&nbsp;Ancy Joseph,&nbsp;Daniel Rauch,&nbsp;Linda Cox,&nbsp;Robert Sprung,&nbsp;Petra Erdmann Gilmore,&nbsp;Qiang Zhang,&nbsp;Robert Reid Townsend,&nbsp;Lianbo Yu,&nbsp;Ayse Selen Yilmaz,&nbsp;Rajeev Aurora,&nbsp;William Park,&nbsp;Lee Ratner,&nbsp;Katherine N. Weilbaecher,&nbsp;Deborah J. Veis","doi":"10.1002/jev2.12516","DOIUrl":"10.1002/jev2.12516","url":null,"abstract":"<p>Adult T cell leukaemia (ATL), caused by infection with human T- lymphotropic virus type 1 (HTLV-1), is often complicated by hypercalcemia and osteolytic lesions. Therefore, we studied the communication between patient-derived ATL cells (ATL-PDX) and HTLV-1 immortalized CD4+ T cell lines (HTLV/T) with osteoclasts and their effects on bone mass in mice. Intratibial inoculation of some HTLV/T leads to a profound local decrease in bone mass similar to marrow-replacing ATL-PDX, despite the fact that few HTLV/T cells persisted in the bone. To study the direct effect of HTLV/T and ATL-PDX on osteoclasts, supernatants were added to murine and human osteoclast precursors. ATL-PDX supernatants from hypercalcemic patients promoted the formation of mature osteoclasts, while those from HTLV/T were variably stimulatory, but had largely consistent effects between human and murine cultures. Interestingly, this osteoclastic activity did not correlate with expression of osteoclastogenic cytokine receptor activator of nuclear factor kappa-B ligand (RANKL), suggesting an alternative mechanism. HTLV/T and ATL-PDX produce small extracellular vesicles (sEV), known to facilitate HTLV-1 infection. We hypothesized that these sEV also mediate bone loss by targeting osteoclasts. We isolated sEV from both HTLV/T and ATL-PDX, and found they carried most of the activity found in supernatants. In contrast, sEV from uninfected activated T cells had little effect. Analysis of sEV (both active and inactive) by mass spectrometry and electron microscopy confirmed absence of RANKL and intact virus. Viral proteins Tax and Env were only present in sEV from the active, osteoclast-stimulatory group, along with increased representation of proteins involved in osteoclastogenesis and bone resorption. sEV from osteoclast-active HTLV/T injected over mouse calvaria in the presence of low-dose RANKL caused more osteolysis than osteoclast-inactive sEV or RANKL alone. Thus, HTLV-1 infection of T cells can cause release of sEV with strong osteolytic potential, providing a mechanism beyond RANKL production that modifies the bone microenvironment, even in the absence of overt leukaemia.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":null,"pages":null},"PeriodicalIF":15.5,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464911/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390976","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":"Phloem sap from melon plants contains extracellular vesicles that carry active proteasomes which increase in response to aphid infestation","authors":"Christian M. Sánchez-López,&nbsp;Carla Soler,&nbsp;Elisa Garzo,&nbsp;Alberto Fereres,&nbsp;Pedro Pérez-Bermúdez,&nbsp;Antonio Marcilla","doi":"10.1002/jev2.12517","DOIUrl":"10.1002/jev2.12517","url":null,"abstract":"<p>The morphogenesis of higher plants requires communication among distant organs throughout vascular tissues (xylem and phloem). Numerous investigations have demonstrated that phloem also act as a distribution route for signalling molecules being observed that different macromolecules translocated by the sap, including nucleic acids and proteins, change under stress situations. The participation of extracellular vesicles (EVs) in this communication has been suggested, although little is known about their role. In fact, in the last decade, the presence of EVs in plants has originated a great controversy, where major concerns arose from their origin, isolation methods, and even the appropriate nomenclature for plant nanovesicles. Phloem sap exudates from melon plants, either aphid-free or infested with <i>Aphis gossypii</i>, were collected by stem incision. After sap concentration (Amicon), phloem EVs (PhlEVs) were isolated by size exclusion chromatography. PhlEVs were characterised using Nanoparticle Tracking Analysis, Transmission electron microscopy and proteomic analysis. Here we confirm the presence of EVs in phloem sap in vivo and the detection of changes in the particles/protein ratio and composition of PhlEVs in response to insect feeding, revealing the presence of typical defence proteins in their cargo as well as components of the proteasome complex. PhlEVs from infested plants showed lower particles/protein ratio and almost two times more proteolytic activity than PhlEVs from aphid-free plants. In both cases, such activity was inhibited in a dose-dependent manner by the proteasome inhibitor MG132. Our results suggest that plants may use this mechanism to prepare themselves to receive infectious agents and open up the possibility of an evolutionary conserved mechanism of defence against pathogens/stresses in eukaryotic organisms.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":null,"pages":null},"PeriodicalIF":15.5,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390977","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":"The emerging role of bacterial extracellular vesicles in human cancers","authors":"Aijun Liang,&nbsp;Lavisha Korani,&nbsp;Cherlie Lot Sum Yeung,&nbsp;Sze Keong Tey,&nbsp;Judy Wai Ping Yam","doi":"10.1002/jev2.12521","DOIUrl":"10.1002/jev2.12521","url":null,"abstract":"<p>Bacterial extracellular vesicles (BEVs) have emerged as pivotal mediators between bacteria and host. In addition to being crucial players in host homeostasis, they have recently been implicated in disease pathologies such as cancer. Hence, the study of BEVs represents an intriguing and rapidly evolving field with substantial translational potential. In this review, we briefly introduce the fundamentals of BEV characteristics, cargo and biogenesis. We emphatically summarize the current relationship between BEVs across various cancer types, illustrating their role in tumorigenesis, treatment responses and patient survival. We further discuss the inherent advantages of BEVs, such as stability, abundance and specific cargo profiles, that make them attractive candidates for non-invasive diagnostic and prognostic approaches. The review also explores the potential of BEVs as a strategy for cancer therapy, considering their ability to deliver therapeutic agents, modulate the tumour microenvironment (TME) and elicit immunomodulatory responses. Understanding the clinical significance of BEVs may lead to the development of better-targeted and personalized treatment strategies. This comprehensive review evaluates the current progress surrounding BEVs and poses questions to encourage further research in this emerging field to harness the benefits of BEVs for their full potential in clinical applications against cancer.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":null,"pages":null},"PeriodicalIF":15.5,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11460218/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390987","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":"Small RNAs in plasma extracellular vesicles define biomarkers of premanifest changes in Huntington's disease","authors":"Marina Herrero-Lorenzo,&nbsp;Jesús Pérez-Pérez,&nbsp;Georgia Escaramís,&nbsp;Saül Martínez-Horta,&nbsp;Rocío Pérez-González,&nbsp;Elisa Rivas-Asensio,&nbsp;Jaime Kulisevsky,&nbsp;Ana Gámez-Valero,&nbsp;Eulàlia Martí","doi":"10.1002/jev2.12522","DOIUrl":"10.1002/jev2.12522","url":null,"abstract":"<p>Despite the advances in the understanding of Huntington's disease (HD), there is a need for molecular biomarkers to categorize mutation carriers during the preclinical stage of the disease preceding functional decline. Small RNAs (sRNAs) are a promising source of biomarkers since their expression levels are highly sensitive to pathobiological processes. Here, using an optimized method for plasma extracellular vesicles (EVs) purification and an exhaustive analysis pipeline of sRNA sequencing data, we show that EV-sRNAs are downregulated early in mutation carriers and that this deregulation is associated with premanifest cognitive performance. Seven candidate sRNAs (tRF-Glu-CTC, tRF-Gly-GCC, miR-451a, miR-21-5p, miR-26a-5p, miR-27a-3p and let7a-5p) were validated in additional subjects, showing a significant diagnostic accuracy at premanifest stages. Of these, miR-21-5p was significantly decreased over time in a longitudinal study; and miR-21-5p and miR-26a-5p levels correlated with cognitive changes in the premanifest cohort. In summary, the present results suggest that deregulated plasma EV-sRNAs define an early biosignature in mutation carriers with specific species highlighting the progression and cognitive changes occurring at the premanifest stage.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":null,"pages":null},"PeriodicalIF":15.5,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.12522","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390986","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":"A critical systematic review of extracellular vesicle clinical trials","authors":"Rachel R. Mizenko,&nbsp;Madison Feaver,&nbsp;Batuhan T. Bozkurt,&nbsp;Neona Lowe,&nbsp;Bryan Nguyen,&nbsp;Kuan-Wei Huang,&nbsp;Aijun Wang,&nbsp;Randy P. Carney","doi":"10.1002/jev2.12510","DOIUrl":"https://doi.org/10.1002/jev2.12510","url":null,"abstract":"<p>This systematic review examines the landscape of extracellular vesicle (EV)-related clinical trials to elucidate the field's trends in clinical applications and EV-related methodologies, with an additional focus on the acknowledgement of EV subpopulations. By analysing data from public reporting repositories, we catalogued 471 EV-related clinical trials to date, with indications for over 200 diseases. Diagnostics and companion diagnostics represented the bulk of EV-related clinical trials with cancer being the most frequent application. EV-related therapeutics trials mainly utilized mesenchymal stromal cell (MSC) EVs and were most frequently used for treatment of respiratory illnesses. Ultracentrifugation and RNA-sequencing were the most common isolation and characterization techniques; however, methodology for each was not frequently reported in study records. Most of the reported characterization relied on bulk characterization of EV isolates, with only 11% utilizing EV subpopulations in their experimental design. While this may be connected to a lack of available techniques suitable for clinical implementation, it also highlights the opportunity for use of EV subpopulations to improve translational efforts. As academic research identifies more chemically distinct subpopulations and technologies for their enrichment, we forecast to more refined EV trials in the near future. This review emphasizes the need for meticulous methodological reporting and consideration of EV subpopulations to enhance the translational success of EV-based interventions, pointing towards a paradigm shift in personalized medicine.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":null,"pages":null},"PeriodicalIF":15.5,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.12510","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142324728","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":"Integrin α6-containing extracellular vesicles promote lymphatic remodelling for pre-metastatic niche formation in lymph nodes via interplay with CD151","authors":"Yan Lin,&nbsp;Hanhao Zheng,&nbsp;Linpei Jia,&nbsp;Yuming Luo,&nbsp;Dingwen Zhang,&nbsp;Mingjie An,&nbsp;Mingrui Pang,&nbsp;Xiayao Diao,&nbsp;Wenjie Li,&nbsp;Jiancheng Chen,&nbsp;Yuanlong Li,&nbsp;Daiyin Liu,&nbsp;Zhicong Liu,&nbsp;Jian Huang,&nbsp;Tianxin Lin,&nbsp;Changhao Chen","doi":"10.1002/jev2.12518","DOIUrl":"https://doi.org/10.1002/jev2.12518","url":null,"abstract":"<p>Heterogeneous extracellular vesicles (EVs) from various types of tumours are acknowledged for inducing the formation of pre-metastatic “niches” in draining lymph nodes (LNs) to promote lymphatic metastasis. In order to identify the specific subpopulations of EVs involved, we performed high-resolution proteomic analysis combined with nanoflow cytometry of bladder cancer (BCa) tissue-derived EVs to identify a novel subset of tumour-derived EVs that contain integrin α6 (ITGA6⁺EVs) and revealed the positive correlation of ITGA6⁺EVs with the formation of pre-metastatic niche in draining LNs and lymphatic metastasis in multicentre clinical analysis of 820-case BCa patients. BCa-derived ITGA6⁺EVs induced E-selectin (SELE)-marked lymphatic remodelling pre-metastatic niche and promoted metastasis in draining LNs through delivering cargo circRNA-<i>LIPAR</i> to lymphatic endothelial cells in vivo and in vitro. Mechanistically, <i>LIPAR</i> linked ITGA6 to the switch II domain of RAB5A and sustained RAB5A GTP-bound activated state, thus maintaining the production of ITGA6⁺EVs loaded with <i>LIPAR</i> through endosomal trafficking. ITGA6⁺EVs targeted lymphatic vessels through ITGA6-CD151 interplay and released <i>LIPAR</i> to induce SELE overexpression-marked lymphatic remodelling pre-metastatic niche. Importantly, we constructed engineered-ITGA6 EVs to inhibit lymphatic pre-metastatic niche, which suppressed lymphatic metastasis and prolonged survival in preclinical models. Collectively, our study uncovers the mechanism of BCa-derived ITGA6⁺EVs mediating pre-metastatic niche and provides an engineered-EV-based strategy against BCa lymphatic metastasis.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":null,"pages":null},"PeriodicalIF":15.5,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.12518","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142324730","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":"MAP kinase kinase 1 (MEK1) within extracellular vesicles inhibits tumour growth by promoting anti-tumour immunity","authors":"Stephen C. Searles,&nbsp;Wei-Shan Chen,&nbsp;Jarrod D. Yee,&nbsp;Preston Lee,&nbsp;Calvin K. Lee,&nbsp;Christine Caron,&nbsp;Felippe Neto,&nbsp;Irina Matei,&nbsp;David Lyden,&nbsp;Jack D. Bui","doi":"10.1002/jev2.12515","DOIUrl":"https://doi.org/10.1002/jev2.12515","url":null,"abstract":"<p>Extracellular vesicles (EVs) mediate intercellular communication in many physiologic processes and can modulate immune responses in individuals with cancer. Most studies of EVs in cancer have focused on their tumour promoting properties. Whether and how EVs might mediate tumour regression besides carrying antigens has not been well characterized. Using a mouse model of highly immunogenic regressor versus poorly immunogenic progressor tumour cells, we have characterized the role of EVs in activating macrophages and promoting tumour rejection. We found that the signalling molecule MAP2K1 (MEK1) is enriched in EVs secreted by regressor relative to progressor cells. Progressor EVs engineered to have levels of MEK1 similar to regressor EVs could inhibit tumour growth by indirectly promoting adaptive immunity in both syngeneic and 3rd party tumours. This effect required MEK1 activity and could occur by activating macrophages to promote adaptive immune responses against the tumour via the cytokine interferon-gamma. Our results suggest that MEK inhibition may be deleterious to cancer treatment, since MEK1 plays an important cell-extrinsic, tumour-suppressive role within EVs. Moreover, the delivery of MEK1 to tumour-associated macrophages, either by EVs, nanoparticles, or some other means, could be a useful strategy to treat cancer via the activation of anti-tumour immunity.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":null,"pages":null},"PeriodicalIF":15.5,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.12515","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142324551","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":"Beyond basic characterization and omics: Immunomodulatory roles of platelet-derived extracellular vesicles unveiled by functional testing","authors":"Mari Palviainen,&nbsp;Johanna Puutio,&nbsp;Rikke Halse Østergaard,&nbsp;Johannes A. Eble,&nbsp;Katariina Maaninka,&nbsp;Umar Butt,&nbsp;Joseph Ndika,&nbsp;Otto K. Kari,&nbsp;Masood Kamali-Moghaddam,&nbsp;Kasper Kjaer-Sorensen,&nbsp;Claus Oxvig,&nbsp;Ana M. Aransay,&nbsp;Juan M. Falcon-Perez,&nbsp;Antonio Federico,&nbsp;Dario Greco,&nbsp;Saara Laitinen,&nbsp;Yuya Hayashi,&nbsp;Pia R.-M. Siljander","doi":"10.1002/jev2.12513","DOIUrl":"https://doi.org/10.1002/jev2.12513","url":null,"abstract":"<p>Renowned for their role in haemostasis and thrombosis, platelets are also increasingly recognized for their contribution in innate immunity, immunothrombosis and inflammatory diseases. Platelets express a wide range of receptors, which allows them to reach a variety of activation endpoints and grants them immunomodulatory functions. Activated platelets release extracellular vesicles (PEVs), whose formation and molecular cargo has been shown to depend on receptor-mediated activation and environmental cues.</p><p>This study compared the immunomodulatory profiles of PEVs generated via activation of platelets by different receptors, glycoprotein VI, C-type lectin-like receptor 2 and combining all thrombin-collagen receptors. Functional assays in vivo in zebrafish and in vitro in human macrophages highlighted distinct homing and secretory responses triggered by the PEVs. In contrast, omics analyses of protein and miRNA cargo combined with physicochemical particle characterization found only subtle differences between the activated PEV types, which were insufficient to predict their different immunomodulatory functions. In contrast, constitutively released PEVs, formed in the absence of an exogenous activator, displayed a distinct immunomodulatory profile from the receptor-induced PEVs.</p><p>Our findings underscore that PEVs are tunable through receptor-mediated activation. To truly comprehend their role(s) in mediating platelet functions among immune cells, conducting functional assays is imperative.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":null,"pages":null},"PeriodicalIF":15.5,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.12513","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142324729","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}