Journal of Extracellular Vesicles最新文献

{"title":"Correction to “Beyond basic characterization and omics: Immunomodulatory roles of platelet-derived extracellular vesicles unveiled by functional testing”","authors":"","doi":"10.1002/jev2.70015","DOIUrl":"10.1002/jev2.70015","url":null,"abstract":"<p>Palviainen, M., Puutio, J., Østergaard, R. H., Eble, J. A., Maaninka, K., Butt, U., Ndika, J., Kari, O. K., Kamali-Moghaddam, M., Kjaer-Sorensen, K., Oxvig, C., Aransay, A. M., Falcon-Perez, J. M., Federico, A., Greco, D., Laitinen, S., Hayashi, Y., &amp; Siljander, P. R.-M. (2024). Beyond basic characterization and omics: Immunomodulatory roles of platelet-derived extracellular vesicles unveiled by functional testing. <i>Journal of Extracellular Vesicles</i>, <i>13</i>, e12513. https://doi.org/10.1002/jev2.12513</p><p></p><p>In Figure 1(f), the 14 hpi column showed the same image in the first row and the second row, whereas it should instead show a high contrast image of the first row following a different colour scheme as correctly shown in the other three columns (1, 4 and 7 hpi). This has been corrected by replacing the image in question. This does not affect the scientific content or the conclusion, since the results have already been fully presented in the first row of images, whereas the second row shows the same results with visual enhancement to highlight two of the three colours for clarity. There was also a typo in the label for the second row “(High constrast)”, which should have read “(High contrast)”.</p><p>In Figure 1(a), in the bright-field image, the scale bar was not fully shown. This has also been corrected by adjusting its position.</p><p>We apologize for these errors.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"13 12","pages":""},"PeriodicalIF":15.5,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11638731/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142818296","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":"Practical advice for extracellular vesicle isolation in plant–microbe interactions: Concerns, considerations, and conclusions","authors":"Hannah Thieron,&nbsp;Laura Krassini,&nbsp;Seomun Kwon,&nbsp;Sebastian Fricke,&nbsp;Sabrine Nasfi,&nbsp;Lorenz Oberkofler,&nbsp;Alessa Ruf,&nbsp;Julia Kehr,&nbsp;Karl-Heinz Kogel,&nbsp;Arne Weiberg,&nbsp;Michael Feldbrügge,&nbsp;Silke Robatzek,&nbsp;Ralph Panstruga","doi":"10.1002/jev2.70022","DOIUrl":"10.1002/jev2.70022","url":null,"abstract":"<p>In recent years, extracellular vesicles (EVs) have emerged as novel key players in plant–microbe interactions. While it is immensely useful to draw on the established “minimal information for studies of extracellular vesicles” (MISEV) guidelines and precedents in mammalian systems, working with plants and their associated microbes poses specific challenges. To navigate researchers through these obstacles, we offer detailed step-by-step suggestions for those embarking on EV research in the context of plant–microbe interactions. The advice is based on recent publications and our collective experience from the diverse plant and microbe systems studied in a dedicated research consortium. We provide considerations for experimental design, optimization, quality control, and recommendations on how to increase yield, purity, and reproducibility of EV isolation. With this perspective article, we aim not only to assist researchers in our field but also to promote discussions on plant and microbe EVs in the broader EV community.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"13 12","pages":""},"PeriodicalIF":15.5,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11635479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813329","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 perspective from the National Eye Institute Extracellular Vesicle Workshop: Gaps, needs, and opportunities for studies of extracellular vesicles in vision research","authors":"Sun Young Lee,&nbsp;Mikael Klingeborn,&nbsp;Jeff W. M. Bulte,&nbsp;Daniel T. Chiu,&nbsp;Michael Chopp,&nbsp;Christopher W. Cutler,&nbsp;Saumya Das,&nbsp;Charles E. Egwuagu,&nbsp;Christie D. Fowler,&nbsp;Sarah F. Hamm-Alvarez,&nbsp;Hakho Lee,&nbsp;Yutao Liu,&nbsp;Ben Mead,&nbsp;Tara L. Moore,&nbsp;Sriram Ravindran,&nbsp;Ashok K. Shetty,&nbsp;Johan Skog,&nbsp;Kenneth W. Witwer,&nbsp;Ali R. Djalilian,&nbsp;Alissa M. Weaver","doi":"10.1002/jev2.70023","DOIUrl":"10.1002/jev2.70023","url":null,"abstract":"<p>With an evolving understanding and new discoveries in extracellular vesicle (EV) biology and their implications in health and disease, the significant diagnostic and therapeutic potential of EVs for vision research has gained recognition. In 2021, the National Eye Institute (NEI) unveiled its Strategic Plan titled ‘Vision for the Future (2021–2025),’ which listed EV research as a priority within the domain of Regenerative Medicine, a pivotal area outlined in the Plan. In alignment with this prioritization, NEI organized a workshop inviting twenty experts from within and beyond the visual system. The workshop aimed to review current knowledge in EV research and explore gaps, needs and opportunities for EV research in the eye, including EV biology and applications of EVs in diagnosis, therapy and prognosis within the visual system. This perspective encapsulates the workshop's deliberations, highlighting the current landscape and potential implications of EV research in advancing eye health and addressing visual diseases.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"13 12","pages":""},"PeriodicalIF":15.5,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11635481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813325","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":"Direct imaging with multidimensional labelling and high-content analysis allows quantitative categorization and characterizations of individual small extracellular vesicles and nanoparticles (sEVPs)","authors":"Simou Sun,&nbsp;Sarah J. Cox-Vázquez,&nbsp;Nam-Joon Cho,&nbsp;Guillermo C. Bazan,&nbsp;Jay T. Groves","doi":"10.1002/jev2.12520","DOIUrl":"10.1002/jev2.12520","url":null,"abstract":"<p>Small extracellular vesicles and nanoparticles (sEVPs) are cell-secreted entities with potential as diagnostic biomarkers and therapeutic vehicles. However, significant intrinsic sEVP heterogeneity impedes analysis and understanding of their composition and functions. We employ multidimensional fluorescent labelling on sEVPs, leveraging the robustness of a newly developed membrane probe—conjugated oligoelectrolytes (COEs), and conduct total internal reflection fluorescence (TIRF) microscopy on sEVP arrays. These arrays comprise single sEVPs anchored to a soft material functionalized surface with little bias. We then develop an enhanced algorithm for colocalization analysis of the multiple labels on individual sEVPs and perform deep profiling of particle content. We categorize sEVPs derived from the same cell type into seven distinct subpopulations—some vesicular whereas others non-vesicular, and we demonstrate that sEVPs from four cell types exhibit quantitatively distinguishable subpopulation distributions. Furthermore, we gain insights into specific particle features within each subpopulation, including CD63 counts, relative particle size, relative concentration of cargoes, and correlations among different cargoes. This high-content analysis reveals common cargo sorting features in sEVP subpopulations across different cell types and suggests new statistics within the sEVP inherent heterogeneity that could differentiate sEVPs from two types of cancer cells and two types of normal cells. Collectively, our study presents a robust single-sEVP characterization platform, combining high-content imaging with comprehensive analysis. This platform is poised to advance sEVP-based theranostic assays and facilitate exploration into disease-associated sEVP biogenesis and sEVP-mediated intercellular communication.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"13 12","pages":""},"PeriodicalIF":15.5,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11635478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813327","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":"Advancing research on parasitic infections: Standardized extracellular vesicle guideline","authors":"Carmen Fernandez-Becerra,&nbsp;Patricia Xander,&nbsp;Martin Olivier,&nbsp;Ana Claudia Torrecilhas","doi":"10.1002/jev2.70009","DOIUrl":"10.1002/jev2.70009","url":null,"abstract":"&lt;p&gt;Parasitic diseases (protozoan and helminths parasites) stand as a significant global health challenge, affecting over a billion people worldwide and claiming millions of lives annually. At the heart of these diseases lie parasites, which instigate a myriad of neglected tropical and infectious diseases. Despite their significant impact on public health, these diseases present challenges in diagnosis, treatment and prevention, largely due to the complex life cycles of the parasites and the intricate nature of host–parasite interactions.&lt;/p&gt;&lt;p&gt;In recent years, the emergence of extracellular vesicles (EVs) as a topic of study has revolutionized our understanding of parasitic infections. These tiny vesicles, secreted by pathogenic protozoa and helminths parasites or infected cells, engage in crucial interactions with host cells, dictating the course of infection and disease progression. These interactions encompass a spectrum of activities crucial for the parasite's survival, including facilitating infection, modulating the host immune response, enhancing host adaptability and transferring factors that confer drug resistance. As conduits of communication between parasites and hosts, EVs hold immense potential as biomarkers for asymptomatic infections and as prognostic indicators for disease outcomes post-therapy.&lt;/p&gt;&lt;p&gt;However, despite the burgeoning interest in EVs, current methodologies for isolating, sizing and characterizing these vesicles often lack the requisite rigor, standardization and quality controls. Recognizing this gap, efforts are underway to establish comprehensive standards drawn from a growing collective understanding.&lt;/p&gt;&lt;p&gt;The journey towards understanding parasite-derived EVs has been marked by collaborative efforts and interdisciplinary dialogues. Workshop titled “Cross-Organism Communication by Extracellular Vesicles: Hosts, Microbes, Parasites (https://doi.org/10.1080/20013078.2017.1407213) organized by the International Society for Extracellular Vesicles (ISEV) workshop in 2016 - São Paulo Brazil” have served as platforms for high-level scientific discussions, exploring the nature, origin, and potential applications of EVs in infectious diseases. These gatherings underscore the need for standardized protocols and techniques for the purification and characterization of EVs, taking into account the unique characteristics of each parasite species and strain.&lt;/p&gt;&lt;p&gt;Our recently published guideline in the &lt;i&gt;Journal of Extracellular Biology&lt;/i&gt; (Fernandez-Becerra et al., &lt;span&gt;2023&lt;/span&gt;), titled “Guidelines for the Purification and Characterization of Extracellular Vesicles of Parasites,” marks a big step forward in this effort. The guideline, written by 31 scientists from around the world, offers a structured framework for isolating, characterizing and investigating EVs obtained from parasite-infected cell cultures, experimental animals and patients.&lt;/p&gt;&lt;p&gt;This editorial aims to highlight the significance of the guideline and","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"13 12","pages":""},"PeriodicalIF":15.5,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11621962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142785370","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":"Enhanced proteomic profiling of human plasma-derived extracellular vesicles through charge-based fractionation to advance biomarker discovery potential","authors":"Xianyi Su,&nbsp;Getúlio Pereira de Oliveira Júnior,&nbsp;Anne-Lise Marie,&nbsp;Michal Gregus,&nbsp;Amanda Figueroa-Navedo,&nbsp;Ionita C. Ghiran,&nbsp;Alexander R. Ivanov","doi":"10.1002/jev2.70024","DOIUrl":"10.1002/jev2.70024","url":null,"abstract":"<p>The study introduces a charge-based fractionation method for fractionating plasma-derived extracellular vesicles (EVs) into sub-populations aimed at the improved purification from free plasma proteins to enhance the diagnostic potential of EV sub-populations for specific pathophysiological states. Here, we present a novel approach for EV fractionation that leverages EVs’ inherent surface charges, differentiating them from other plasma components and, thus, reducing the sample complexity and increasing the purity of EVs. The developed method was optimized and thoroughly evaluated using proteomic analysis, transmission electron microscopy, nanoparticle tracking, and western blotting of isolated EVs from healthy donors. Subsequently, we pilot-tested the developed technique for its applicability to real-world specimens using a small set of clinical prostate cancer samples and matched controls. The presented technique demonstrates the effective isolation and fractionation of EV sub-populations based on their surface charge, which may potentially help enhance EV-based diagnostics, biomarker discovery, and basic biology research. The method is designed to be straightforward, scalable, easy-to-use, and it does not require specialized skills or equipment.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"13 12","pages":""},"PeriodicalIF":15.5,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11621968/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142785506","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":"Dopamine-conjugated extracellular vesicles induce autophagy in Parkinson's disease","authors":"Jae Hoon Sul,&nbsp;Sol Shin,&nbsp;Hark Kyun Kim,&nbsp;Jihoon Han,&nbsp;Junsik Kim,&nbsp;Soyong Son,&nbsp;Jungmi Lee,&nbsp;Seung Hyun Baek,&nbsp;Yoonsuk Cho,&nbsp;Jeongmi Lee,&nbsp;Jinsu Park,&nbsp;Donghoon Ahn,&nbsp;Sunyoung Park,&nbsp;Leon F. Palomera,&nbsp;Jeein Lim,&nbsp;Jongho Kim,&nbsp;Chanhee Kim,&nbsp;Seungsu Han,&nbsp;Ka Young Chung,&nbsp;Sangho Lee,&nbsp;Tae-in Kam,&nbsp;Yunjong Lee,&nbsp;Jeongyun Kim,&nbsp;Jae Hyung Park,&nbsp;Dong-Gyu Jo","doi":"10.1002/jev2.70018","DOIUrl":"10.1002/jev2.70018","url":null,"abstract":"<p>The application of extracellular vesicles (EVs) as vehicles for anti-Parkinson's agents represents a significant advance, yet their clinical translation is hampered by challenges in efficient brain delivery and complex blood-brain barrier (BBB) targeting strategies. In this study, we engineered dopamine onto the surface of adipose-derived stem cell EVs (Dopa-EVs) utilizing a facile, two-step cross-linking approach. This engineering enhanced neuronal uptake of the EVs in primary neurons and neuroblastoma cells, a process shown to be competitively inhibited by dopamine pretreatment and dopamine receptor antibodies. Notably, Dopa-EVs demonstrated increased brain accumulation in mouse Parkinson's disease (PD) models. Therapeutically, Dopa-EVs administration led to the rescue of dopaminergic neuronal loss and amelioration of behavioural deficits in both 6-hydroxydopamine (6-OHDA) and α-Syn PFF-induced PD models. Furthermore, we observed that Dopa-EVs stimulated autophagy evidenced by the upregulation of Beclin-1 and LC3-II. These findings collectively indicate that surface modification of EVs with dopamine presents a potent strategy for targeting dopaminergic neurons in the brain. The remarkable therapeutic potential of Dopa-EVs, demonstrated in PD models, positions them as a highly promising candidate for PD treatment, offering a significant advance over current therapeutic modalities.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"13 12","pages":""},"PeriodicalIF":15.5,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11621972/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142785505","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, RNA sequencing, and bioinformatic analyses: Challenges, solutions, and recommendations","authors":"Rebecca T. Miceli,&nbsp;Tzu-Yi Chen,&nbsp;Yohei Nose,&nbsp;Swapnil Tichkule,&nbsp;Briana Brown,&nbsp;John F. Fullard,&nbsp;Marilyn D. Saulsbury,&nbsp;Simon O. Heyliger,&nbsp;Sacha Gnjatic,&nbsp;Natasha Kyprianou,&nbsp;Carlos Cordon-Cardo,&nbsp;Susmita Sahoo,&nbsp;Emanuela Taioli,&nbsp;Panos Roussos,&nbsp;Gustavo Stolovitzky,&nbsp;Edgar Gonzalez-Kozlova,&nbsp;Navneet Dogra","doi":"10.1002/jev2.70005","DOIUrl":"https://doi.org/10.1002/jev2.70005","url":null,"abstract":"<p>Extracellular vesicles (EVs) are heterogeneous entities secreted by cells into their microenvironment and systemic circulation. Circulating EVs carry functional small RNAs and other molecular footprints from their cell of origin, and thus have evident applications in liquid biopsy, therapeutics, and intercellular communication. Yet, the complete transcriptomic landscape of EVs is poorly characterized due to critical limitations including variable protocols used for EV-RNA extraction, quality control, cDNA library preparation, sequencing technologies, and bioinformatic analyses. Consequently, there is a gap in knowledge and the need for a standardized approach in delineating EV-RNAs. Here, we address these gaps by describing the following points by (1) focusing on the large canopy of the EVs and particles (EVPs), which includes, but not limited to – exosomes and other large and small EVs, lipoproteins, exomeres/supermeres, mitochondrial-derived vesicles, RNA binding proteins, and cell-free DNA/RNA/proteins; (2) examining the potential functional roles and biogenesis of EVPs; (3) discussing various transcriptomic methods and technologies used in uncovering the cargoes of EVPs; (4) presenting a comprehensive list of RNA subtypes reported in EVPs; (5) describing different EV-RNA databases and resources specific to EV-RNA species; (6) reviewing established bioinformatics pipelines and novel strategies for reproducible EV transcriptomics analyses; (7) emphasizing the significant need for a gold standard approach in identifying EV-RNAs across studies; (8) and finally, we highlight current challenges, discuss possible solutions, and present recommendations for robust and reproducible analyses of EVP-associated small RNAs. Overall, we seek to provide clarity on the transcriptomics landscape, sequencing technologies, and bioinformatic analyses of EVP-RNAs. Detailed portrayal of the current state of EVP transcriptomics will lead to a better understanding of how the RNA cargo of EVPs can be used in modern and targeted diagnostics and therapeutics. For the inclusion of different particles discussed in this article, we use the terms large/small EVs, non-vesicular extracellular particles (NVEPs), EPs and EVPs as defined in MISEV guidelines by the International Society of Extracellular Vesicles (ISEV).</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"13 12","pages":""},"PeriodicalIF":15.5,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142764330","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":"Monocyte-derived extracellular vesicles, stimulated by Trypanosoma cruzi, enhance cellular invasion in vitro via activated TGF-β1","authors":"Ephraim A. Ansa-Addo,&nbsp;Paras Pathak,&nbsp;Maria V. McCrossan,&nbsp;Izadora Volpato Rossi,&nbsp;Mahamed Abdullahi,&nbsp;Dan Stratton,&nbsp;Sigrun Lange,&nbsp;Marcel I. Ramirez,&nbsp;Jameel M. Inal","doi":"10.1002/jev2.70014","DOIUrl":"https://doi.org/10.1002/jev2.70014","url":null,"abstract":"<p>During cell invasion, large Extracellular Vesicle (lEV) release from host cells was dose-dependently triggered by <i>Trypanosoma cruzi</i> metacyclic trypomastigotes (Mtr). This lEV release was inhibited when IP₃-mediated Ca²⁺ exit from the ER and further Ca²⁺ entry from plasma membrane channels was blocked, but whilst any store-independent Ca²⁺ entry (SICE) could continue unabated. That lEV release was equally inhibited if all entry from external sources was blocked by chelation of external Ca²⁺ points to the major contributor to Mtr-triggered host cell lEV release being IP₃/store-mediated Ca²⁺ release, SICE playing a minor role. Host cell lEVs were released through Mtr interaction with host cell lipid raft domains, integrins, and mechanosensitive ion channels, whereupon [Ca²⁺]_cyt increased (50 to 750 nM) within 15 s. lEV release and cell entry of <i>T. cruzi</i>, which increased up to 30 and 60 mpi, respectively, as well as raised actin depolymerization at 60 mpi, were all reduced by TRPC inhibitor, GsMTx-4. Vesicle release and infection was also reduced with RGD peptide, methyl-β-cyclodextrin, knockdown of calpain and with the calpain inhibitor, calpeptin. Restoration of lEV levels, whether with lEVs from infected or uninfected epithelial cells, did not restore invasion, but supplementation with lEVs from infected monocytes, did. We provide evidence of THP-1 monocyte-derived lEV interaction with Mtr (lipid mixing by R18-dequenching; flow cytometry showing transfer to Mtr of R18 from R18-lEVs and of LAP(TGF-β1). Active, mature TGF-β1 (at 175 pg/×10⁵ in THP-1 lEVs) was detected in concentrated lEV-/cell-free supernatant by western blotting, only after THP-1 lEVs had interacted with Mtr. The TGF-β1 receptor (TβRI) inhibitor, SB-431542, reduced the enhanced cellular invasion due to monocyte-lEVs.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"13 11","pages":""},"PeriodicalIF":15.5,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749253","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":"Glycoengineered extracellular vesicles released from antibacterial hydrogel facilitate diabetic wound healing by promoting angiogenesis","authors":"Kewei Wang,&nbsp;Qin He,&nbsp;Mengmeng Yang,&nbsp;Qincheng Qiao,&nbsp;Jun Chen,&nbsp;Jia Song,&nbsp;Nan Zang,&nbsp;Huiqing Hu,&nbsp;Longqing Xia,&nbsp;Yingyue Xiang,&nbsp;Fei Yan,&nbsp;Xinguo Hou,&nbsp;Li Chen","doi":"10.1002/jev2.70013","DOIUrl":"10.1002/jev2.70013","url":null,"abstract":"<p>Diabetic wounds have become a global healthcare burden owing to impaired angiogenesis and persistent infections. Extracellular vesicles (EVs) can improve diabetic wounds, though their targeting ability is limited. In this study, we investigated the performance of a novel hydrogel dressing comprised of gelatin methacryloyl, glycoengineered EVs, and polylysine in treating infected diabetic wounds. High-throughput single-cell RNA sequencing (scRNA-seq) and immunofluorescence staining revealed that E-selectin (SELE) levels were higher in diabetic wounds than in non-diabetic wounds. Mesenchymal stromal cells (MSCs) were transfected with a lentivirus containing fucosyltransferase VII (FUT7) and a CD63-P19-Nluc vector to enhance the expression of sialyl Lewis X (sLeX), the ligand of E-selectin, on the surface of EVs (s-EVs) derived from transfected MSCs (s-MSCs). s-EVs can target human umbilical vein endothelial cells (HUVECs) under lipopolysaccharide stimulation and promote the function of stimulated HUVECs in vitro. To promote and sustain the release of s-EVs, we fabricated a gelatin methacryloyl (Gel)/poly-L-lysine methacryloyl (PL)-5 hydrogel with good antibacterial ability, biocompatibility and mechanical properties. In a mouse experiment, s-EV@Gel/PL-5 exhibited excellent angiogenesis and anti-inflammatory abilities and further promoted the healing of infected diabetic wounds. Our findings demonstrated the potential of the s-EV@Gel/PL-5 hydrogel in the clinical treatment of diabetic infectious wounds.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"13 11","pages":""},"PeriodicalIF":15.5,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142729525","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}