Journal of Extracellular Vesicles最新文献

{"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}

{"title":"Extracellular vesicle isolation methods identify distinct HIV-1 particles released from chronically infected T-cells","authors":"Sebastian M. Molnar,&nbsp;Yuriy Kim,&nbsp;Lindsay Wieczorek,&nbsp;Anastasia Williams,&nbsp;Kajal Ashok Patil,&nbsp;Pooja Khatkar,&nbsp;Mark F. Santos,&nbsp;Gifty Mensah,&nbsp;Aurelio Lorico,&nbsp;Victoria R. Polonis,&nbsp;Fatah Kashanchi","doi":"10.1002/jev2.12476","DOIUrl":"10.1002/jev2.12476","url":null,"abstract":"<p>The current study analyzed the intersecting biophysical, biochemical, and functional properties of extracellular particles (EPs) with the human immunodeficiency virus type-1 (HIV-1) beyond the currently accepted size range for HIV-1. We isolated five fractions (Frac-A through Frac-E) from HIV-infected cells by sequential differential ultracentrifugation (DUC). All fractions showed a heterogeneous size distribution with median particle sizes greater than 100 nm for Frac-A through Frac-D but not for Frac-E, which contained small EPs with an average size well below 50 nm. Synchronized and released cultures contained large infectious EPs in Frac-A, with markers of amphisomes and viral components. Additionally, Frac-E uniquely contained EPs positive for CD63, HSP70, and HIV-1 proteins. Despite its small average size, Frac-E contained membrane-protected viral integrase, detectable only after SDS treatment, indicating that it is enclosed in vesicles. Single particle analysis with dSTORM further supported these findings as CD63, HIV-1 integrase, and the viral surface envelope (Env) glycoprotein (gp) colocalized on the same Frac-E particles. Surprisingly, Frac-E EPs were infectious, and infectivity was significantly reduced by immunodepleting Frac-E with anti-CD63, indicating the presence of this protein on the surface of infectious small EPs in Frac-E. To our knowledge, this is the first time that extracellular vesicle (EV) isolation methods have identified infectious small HIV-1 particles (_smHIV-1) that are under 50 nm. Collectively, our data indicate that the crossroads between EPs and HIV-1 potentially extend beyond the currently accepted biophysical properties of HIV-1, which may have further implications for viral pathogenesis.</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/PMC11231049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141558885","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 immunomodulatory ballet of tumour-derived extracellular vesicles and neutrophils orchestrating the dynamic CD73/PD-L1 pathway in cancer","authors":"Dominique S. Rubenich,&nbsp;Jordana L. Domagalski,&nbsp;Gabriela F. S. Gentil,&nbsp;Jonas Eichberger,&nbsp;Mathias Fiedler,&nbsp;Florian Weber,&nbsp;Marianne Federlin,&nbsp;Hendrik Poeck,&nbsp;Torsten E. Reichert,&nbsp;Tobias Ettl,&nbsp;Richard J. Bauer,&nbsp;Elizandra Braganhol,&nbsp;Daniela Schulz","doi":"10.1002/jev2.12480","DOIUrl":"10.1002/jev2.12480","url":null,"abstract":"<p>Head and neck squamous cell carcinoma (HNSCC) is a global cancer burden with a 5-year overall survival rate of around 50%, stagnant for decades. A tumour-induced immunosuppressive microenvironment contributes to HNSCC progression, with the adenosine (ADO) pathway and an upregulated expression of inhibitory immune checkpoint regulators playing a key role in this context. The correlation between high neutrophil-to-lymphocyte ratio (NLR) with advanced tumour staging suggests involvement of neutrophils (NØ) in cancer progression. Interestingly, we associated a high NLR with an increased intracellular PD-L1 localization in primary HNSCC samples, potentially mediating more aggressive tumour characteristics and therefore synergistically favouring tumour progression. Still, further research is needed to harness this knowledge for effective treatments and overcome resistance. Since it is hypothesized that the tumour microenvironment (TME) may be influenced by small extracellular vesicles (sEVs) secreted by tumours (TEX), this study aims to investigate the impact of HNSCC-derived TEX on NØ and blockade of ADO receptors as a potential strategy to reverse the pro-tumour phenotype of NØ. UMSCC47-TEX exhibited CD73 enzymatic activity involved in ADO signalling, as well as the immune checkpoint inhibitor PD-L1. Data revealed that TEX induce chemotaxis of NØ and the sustained interaction promotes a shift into a pro-tumour phenotype, dependent on ADO receptors (P1R), increasing CD170^high subpopulation, CD73 and PD-L1 expression, followed by an immunosuppressive secretome. Blocking A3R reduced CD73 and PD-L1 expression. Co-culture experiments with HNSCC cells demonstrated that TEX-modulated NØ increase the CD73/PD-L1 axis, through Cyclin D-CDK4/6 signalling. To support these findings, the CAM model with primary tumour was treated with NØ supernatant. Moreover, these NØ promoted an increase in migration, invasion, and reduced cell death. Targeting P1R on NØ, particularly A3R, exhibited potential therapeutic strategy to counteract immunosuppression in HNSCC. Understanding the TEX-mediated crosstalk between tumours and NØ offers insights into immunomodulation for improving cancer therapies.</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/PMC11231043/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141558910","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":"HaloTag display enables quantitative single-particle characterisation and functionalisation of engineered extracellular vesicles","authors":"Roxana E. Mitrut,&nbsp;Devin M. Stranford,&nbsp;Beth N. DiBiase,&nbsp;Jonathan M. Chan,&nbsp;Matthew D. Bailey,&nbsp;Minrui Luo,&nbsp;Clare S. Harper,&nbsp;Thomas J. Meade,&nbsp;Muzhou Wang,&nbsp;Joshua N. Leonard","doi":"10.1002/jev2.12469","DOIUrl":"10.1002/jev2.12469","url":null,"abstract":"<p>Extracellular vesicles (EVs) play key roles in diverse biological processes, transport biomolecules between cells and have been engineered for therapeutic applications. A useful EV bioengineering strategy is to express engineered proteins on the EV surface to confer targeting, bioactivity and other properties. Measuring how incorporation varies across a population of EVs is important for characterising such materials and understanding their function, yet it remains challenging to quantitatively characterise the absolute number of engineered proteins incorporated at single-EV resolution. To address these needs, we developed a HaloTag-based characterisation platform in which dyes or other synthetic species can be covalently and stoichiometrically attached to engineered proteins on the EV surface. To evaluate this system, we employed several orthogonal quantification methods, including flow cytometry and fluorescence microscopy, and found that HaloTag-mediated quantification is generally robust across EV analysis methods. We compared HaloTag-labelling to antibody-labelling of EVs using single vesicle flow cytometry, enabling us to measure the substantial degree to which antibody labelling can underestimate proteins present on an EV. Finally, we demonstrate the use of HaloTag to compare between protein designs for EV bioengineering. Overall, the HaloTag system is a useful EV characterisation tool which complements and expands existing methods.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"13 7","pages":""},"PeriodicalIF":15.5,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.12469","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141534544","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 new subtype of artificial cell-derived vesicles from dental pulp stem cells with the bioequivalence and higher acquisition efficiency compared to extracellular vesicles","authors":"Xingxiang Duan,&nbsp;Rui Zhang,&nbsp;Huixian Feng,&nbsp;Heng Zhou,&nbsp;Yu Luo,&nbsp;Wei Xiong,&nbsp;Junyi Li,&nbsp;Yan He,&nbsp;Qingsong Ye","doi":"10.1002/jev2.12473","DOIUrl":"10.1002/jev2.12473","url":null,"abstract":"<p>Extracellular vesicles (EVs) derived from dental pulp stem cells (DPSC) have been shown an excellent efficacy in a variety of disease models. However, current production methods fail to meet the needs of clinical treatment. In this study, we present an innovative approach to substantially enhance the production of ‘Artificial Cell-Derived Vesicles (ACDVs)’ by extracting and purifying the contents released by the DPSC lysate, namely intracellular vesicles. Comparative analysis was performed between ACDVs and those obtained through ultracentrifugation. The ACDVs extracted from the cell lysate meet the general standard of EVs and have similar protein secretion profile. The new ACDVs also significantly promoted wound healing, increased or decreased collagen regeneration, and reduced the production of inflammatory factors as the EVs. More importantly, the extraction efficiency is improved by 16 times compared with the EVs extracted using ultracentrifuge method. With its impressive attributes, this new subtype of ACDVs emerge as a prospective candidate for the future clinical applications in regenerative medicine.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"13 7","pages":""},"PeriodicalIF":15.5,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.12473","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141534543","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 systematic review and meta-analysis of clinical trials assessing safety and efficacy of human extracellular vesicle-based therapy","authors":"Mats Van Delen,&nbsp;Judith Derdelinckx,&nbsp;Kristien Wouters,&nbsp;Inge Nelissen,&nbsp;Nathalie Cools","doi":"10.1002/jev2.12458","DOIUrl":"10.1002/jev2.12458","url":null,"abstract":"<p>Nowadays, it has become clear that extracellular vesicles (EVs) are not a cellular waste disposal vesicle but are an essential part of an intercellular communication system. Besides the use of EVs in biomarker studies and diagnostics, the potential of EV-therapeutics has been seen by many. They provide unique properties for disease therapy, including strong immune-modulatory actions, the possibility of engineering, low immunogenicity, and the capability of crossing biological barriers. Proof-of-concept of EV-therapeutics for various pathologies has been achieved in preclinical studies. However, clinical trials with EVs have only been emerging slowly. Here, we aim to provide a comprehensive overview of the current state-of-the-art concerning clinical studies using EVs in human therapy. By approaching the current knowledge in a systematic manner, we were able to include 21 reports for meta-analysis of safety and evaluation of efficacy outcomes. Overall, we have shown that EV-based therapy is safe with a low incidence of serious adverse events (SAE; 0.7% (95%-CI: 0.1–5.2%), and adverse events (AE; 4.4% (95%-CI: 0.7–22.2%). Subgroup analysis showed no significant difference in SAE when comparing autologous versus allogeneic administration, as well as engineered versus non-engineered EV products. A significantly higher number of AE was seen in autologous versus allogeneic administration. However, the clinical relevance remains questionable. Evaluation of the clinical outcomes of immunostimulatory, immunosuppressive or regenerative EV-therapies indicated improvement in the majority of treated patients. Despite these promising results, data need to be approached with caution due to a high heterogeneity in the EVs manufacturing methods, study design, and reporting of (S)AE. Overall, we conclude that EV-based therapy is safe and presents a promising opportunity in therapy. More efforts are needed in the standardization and harmonization of reporting of EV isolation and characterization data as well as in the reporting of (S)AE to allow inter-study comparison.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"13 7","pages":""},"PeriodicalIF":15.5,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11220457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141492271","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":"AAV gene replacement therapy for treating MPS IIIC: Facilitating bystander effects via EV-mRNA cargo","authors":"Tierra A. Bobo,&nbsp;Michael Robinson,&nbsp;Christopher Tofade,&nbsp;Marina Sokolski-Papkov,&nbsp;Peter Nichols,&nbsp;Stephen Vorobiov,&nbsp;Haiyan Fu","doi":"10.1002/jev2.12464","DOIUrl":"10.1002/jev2.12464","url":null,"abstract":"<p>MPS IIIC is a lysosomal storage disease caused by mutations in heparan-α-glucosaminide <i>N</i>-acetyltransferase (HGSNAT), for which no treatment is available. Because HGSNAT is a trans-lysosomal-membrane protein, gene therapy for MPS IIIC needs to transduce as many cells as possible for maximal benefits. All cells continuously release extracellular vesicles (EVs) and communicate by exchanging biomolecules via EV trafficking. To address the unmet need, we developed a rAAV-hHGSNAT^EV vector with an EV-mRNA-packaging signal in the 3′UTR to facilitate bystander effects, and tested it in an in vitro MPS IIIC model. In human MPS IIIC cells, rAAV-hHGSNAT^EV enhanced HGSNAT mRNA and protein expression, EV-hHGSNAT-mRNA packaging, and cleared GAG storage. Importantly, incubation with EVs led to hHGSNAT protein expression and GAG contents clearance in recipient MPS IIIC cells. Further, rAAV-hHGSNAT^EV transduction led to the reduction of pathological EVs in MPS IIIC cells to normal levels, suggesting broader therapeutic benefits. These data demonstrate that incorporating the EV-mRNA-packaging signal into a rAAV-hHGSNAT vector enhances EV packaging of hHGSNAT-mRNA, which can be transported to non-transduced cells and translated into functional rHGSNAT protein, facilitating cross-correction of disease pathology. This study supports the therapeutic potential of rAAV^EV for MPS IIIC, and broad diseases, without having to transduce every cell.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"13 7","pages":""},"PeriodicalIF":15.5,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.12464","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141498167","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":"Oxidative stress induces extracellular vesicle release by upregulation of HEXB to facilitate tumour growth in experimental hepatocellular carcinoma","authors":"Jiufei Duan,&nbsp;Zhao Huang,&nbsp;Siyuan Qin,&nbsp;Bowen Li,&nbsp;Zhe Zhang,&nbsp;Rui Liu,&nbsp;Kui Wang,&nbsp;Edouard C. Nice,&nbsp;Jingwen Jiang,&nbsp;Canhua Huang","doi":"10.1002/jev2.12468","DOIUrl":"10.1002/jev2.12468","url":null,"abstract":"<p>Extracellular vesicles (EVs) play a crucial role in triggering tumour-aggressive behaviours. However, the energetic process by which tumour cells produce EVs remains poorly understood. Here, we demonstrate the involvement of <i>β</i>-hexosaminidase B (HEXB) in mediating EV release in response to oxidative stress, thereby promoting the development of hepatocellular carcinoma (HCC). Mechanistically, reactive oxygen species (ROS) stimulate the nuclear translocation of transcription factor EB (TFEB), leading to the upregulation of both HEXB and its antisense lncRNA HEXB-AS. HEXB-AS can bind HEXB to form a protein/RNA complex, which elevates the protein stability of HEXB. The stabilized HEXB interacts with lysosome-associated membrane glycoprotein 1 (LAMP1), disrupting lysosome-multivesicular body (MVB) fusion, which protects EVs from degradation. Knockdown of HEXB efficiently inhibits EV release and curbs HCC growth both in vitro and in vivo. Moreover, targeting HEXB by M-31850 significantly inhibits HCC growth, especially when combined with GW4869, an inhibitor of exosome release. Our results underscore the critical role of HEXB as a modulator that promotes EV release during HCC development.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"13 7","pages":""},"PeriodicalIF":15.5,"publicationDate":"2024-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11214608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141468459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular vesicles originating from melanoma cells promote dysregulation in haematopoiesis as a component of cancer immunoediting","authors":"Doste R. Mamand,&nbsp;Safa Bazaz,&nbsp;Dara K. Mohammad,&nbsp;Xiuming Liang,&nbsp;Svetlana Pavlova,&nbsp;Carsten Mim,&nbsp;Susanne Gabrielsson,&nbsp;Joel Z. Nordin,&nbsp;Oscar P. B. Wiklander,&nbsp;Manuchehr Abedi-Valugerdi,&nbsp;Samir EL-Andaloussi","doi":"10.1002/jev2.12471","DOIUrl":"10.1002/jev2.12471","url":null,"abstract":"<p>Haematopoiesis dysregulation with the presence of immature myeloid and erythroid immunosuppressive cells are key characteristics of the immune escape phase of tumour development. Here, the role of in vitro generated B16F10 tumour cell-derived extracellular vesicles (tEVs) as indirect cellular communicators, participating in tumour-induced dysregulation of haematopoiesis, was explored. The isolated tEVs displayed features of small EVs with a size range of 100–200 nm, expressed the common EV markers CD63, CD9, and Alix, and had a spherical shape with a lipid bilayer membrane. Proteomic profiling revealed significant levels of angiogenic factors, particularly vascular endothelial growth factor (VEGF), osteopontin, and tissue factor, associated with the tEVs. Systemic administration of these tEVs in syngeneic mice induced splenomegaly and disrupted haematopoiesis, leading to extramedullary haematopoiesis, expansion of splenic immature erythroid progenitors, reduced bone marrow cellularity, medullary expansion of granulocytic myeloid suppressor cells, and the development of anaemia. These effects closely mirrored those observed in tumour-bearing mice and were not seen after heat inactivating the tEVs. In vitro studies demonstrated that tEVs independently induced the expansion of bone marrow granulocytic myeloid suppressor cells and B cells while reducing the frequency of cells in the erythropoietic lineage. These effects of tEVs were significantly abrogated by the blockade of VEGF or heat inactivation. Our findings underscore the important role of tEVs in dysregulating haematopoiesis during the immune escape phase of cancer immunoediting, suggesting their potential as targets for addressing immune evasion and reinstating normal hematopoietic processes.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"13 7","pages":""},"PeriodicalIF":15.5,"publicationDate":"2024-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11214607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141468458","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":"Therapeutics of the future: Navigating the pitfalls of extracellular vesicles research from an osteoarthritis perspective","authors":"Antoine Karoichan,&nbsp;Sarah Boucenna,&nbsp;Maryam Tabrizian","doi":"10.1002/jev2.12435","DOIUrl":"10.1002/jev2.12435","url":null,"abstract":"<p>Extracellular vesicles have gained wide momentum as potential therapeutics for osteoarthritis, a highly prevalent chronic disease that still lacks an approved treatment. The membrane-bound vesicles are secreted by all cells carrying different cargos that can serve as both disease biomarkers and disease modifiers. Nonetheless, despite a significant peak in research regarding EVs as OA therapeutics, clinical implementation seems distant. In addition to scalability and standardization challenges, researchers often omit to focus on and consider the proper tropism of the vesicles, the practicality and relevance of their source, their low native therapeutic efficacy, and whether they address the disease as a whole. These considerations are necessary to better understand EVs in a clinical light and have been comprehensively discussed and ultimately summarized in this review into a conceptualized framework termed the nanodiamond concept. Future perspectives are also discussed, and alternatives are presented to address some of the challenges and concerns.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"13 7","pages":""},"PeriodicalIF":15.5,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11213691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141468460","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}