{"title":"The 3rd annual American Society for Intercellular Communication (ASIC) meeting, 2023 conference report.","authors":"Ashley E Russell, Aurelio Lorico","doi":"10.20517/evcna.2024.64","DOIUrl":"10.20517/evcna.2024.64","url":null,"abstract":"","PeriodicalId":520322,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"5 4","pages":"628-638"},"PeriodicalIF":0.0,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11725420/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142985727","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":"Mesenchymal stromal cells-extracellular vesicles: protein corona as a camouflage mechanism?","authors":"Enrico Ragni, Michela Taiana","doi":"10.20517/evcna.2024.78","DOIUrl":"10.20517/evcna.2024.78","url":null,"abstract":"<p><p>Mesenchymal stromal cells (MSCs) showed promising potential for regenerative and therapeutic applications for several pathologies and conditions. Their potential is mainly ascribed to the factors and extracellular vesicles (EVs) they release, which are now envisioned as cell-free therapeutics in cutting-edge clinical studies. A main cornerstone is the preferential uptake by target cells and tissues, in contrast to clearance by phagocytic cells or removal from circulation before reaching the final destination. Recent literature has suggested how the surface properties of EVs might influence their half-life, bio-distribution, and specific uptake. In particular, the concept of a protein corona surrounding EVs emerged. Especially for culture-purified EVs, the process of tailoring a treatment or tissue-specific corona was explored. Liam-Or <i>et al</i>. examined the impact of protein corona on MSC-EVs when specific proteins, preferentially albumin, were adsorbed from media on the EV surface before isolation. This resulted in improved uptake by liver parenchymal cells and reduced incorporation by macrophages, together with an increased half-life in the circulation system. Thus, producing MSC-EVs with an albumin-enriched protein corona might be a camouflage strategy to enhance non-phagocytic uptake in the liver. This research might be a milestone for future studies on other EVs-camouflage approaches tailored to specific tissues and therapeutic applications.</p>","PeriodicalId":520322,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"5 4","pages":"622-627"},"PeriodicalIF":0.0,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11725427/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142985611","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":"Engineered extracellular vesicles as \"supply vehicles\" to alleviate type 1 diabetes.","authors":"Fei Wang, Zhenhua Li","doi":"10.20517/evcna.2024.61","DOIUrl":"10.20517/evcna.2024.61","url":null,"abstract":"<p><p>Recent findings have indicated that the deficiency of inhibitory programmed cell death ligand 1 (PD-L1) and galectin-9 (Gal-9) in pancreatic β-cells is associated with the progression of type 1 diabetes (T1D). This suggests that exogenous PD-L1 and Gal-9 may have promising potential as therapeutics for the treatment of T1D. In light of these reports, a recent work investigated the potential of artificial extracellular vesicles (aEVs) with the presentation of PD-L1 and Gal-9 ligands (PD-L1-Gal-9 aEVs) as a treatment for T1D, with the findings published in <i>Diabetes</i>. Notably, the PD-L1-Gal-9 aEVs demonstrated the capacity to induce apoptosis of T cells and the formation of regulatory T (Treg) cells, thereby maintaining immune tolerance. Furthermore, the <i>in vivo</i> administration of PD-L1-Gal-9 aEVs resulted in a reduction in T cell infiltration in the pancreas, an increase in β-cell integrity protection, a significant decrease in blood glucose levels, and a delay in the progression of T1D. In conclusion, this study proposed an innovative approach to the treatment of T1D progression through the use of immunosuppressive EVs. This highlight provides a comprehensive analysis and discussion of the pivotal findings of this study.</p>","PeriodicalId":520322,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"5 4","pages":"618-621"},"PeriodicalIF":0.0,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11725422/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142985566","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":"Combining Cre-LoxP and single-cell sequencing technologies: insights into the extracellular vesicle cargo transfer.","authors":"Michael W Pfaffl","doi":"10.20517/evcna.2024.58","DOIUrl":"10.20517/evcna.2024.58","url":null,"abstract":"<p><p>The recent study from the Pogge von Strandmann group published in <i>Cellular and Molecular Immunology</i>, by Alashkar Alhamwe <i>et al</i>., combined for the first time the Cre-LoxP recombination system with single-cell sequencing. The group monitored the tumor-derived extracellular vesicle (EV) uptake and the EV functions in the recipient non-malignant cells in a pancreatic ductal adenocarcinoma mouse model. Recombination events and EV uptake, together with resulting gene expression changes in macrophages, neutrophils, and mast cells, were detected by single-cell sequencing technology of the tumor tissue. This new approach is highly specific, as it can identify single EV recipient cells without interfering with the EV biogenesis or the phenotype.</p>","PeriodicalId":520322,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"5 4","pages":"614-617"},"PeriodicalIF":0.0,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11725425/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142985501","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}
Xin Lu, Ziwen Yu, Junjun Wang, Ao Tian, Tingyu Wu, Yirui Cheng, Qing Han, Fan Li, Weiliang Xia
{"title":"The unexpected PD-L1 suppression function of celery-derived extracellular vesicles improves lung cancer chemotherapy efficacy.","authors":"Xin Lu, Ziwen Yu, Junjun Wang, Ao Tian, Tingyu Wu, Yirui Cheng, Qing Han, Fan Li, Weiliang Xia","doi":"10.20517/evcna.2023.75","DOIUrl":"10.20517/evcna.2023.75","url":null,"abstract":"<p><p><b>Aim:</b> The article explores celery-derived extracellular vesicles (CDEVs), characterized by high cellular uptake, low immunogenicity, and high stability, as a therapeutic strategy for antitumor nanomedicines. <b>Methods:</b> The methods employed in this study include <i>in vitro</i> cell experiments such as co-culture, Western Blot, and flow cytometry. <i>In vivo</i> experiments were conducted in C57BL/6 tumor-bearing mice subcutaneously injected with Lewis lung carcinoma (LLC) cells. The experiments encompassed parameters such as survival rate, body weight, tumor size, flow cytometry, immunohistochemistry, and spectral live imaging system. <b>Results:</b> Our study revealed that CDEVs could be used as drugs to effectively downregulate the phosphorylated signal transducer and activator of transcription 3 (p-STAT3)/programmed cell death ligand 1 (PD-L1) axis in lung cancer cells. In co-culture experiments, CDEVs were observed to impede the expression of PD-L1, thereby interfering with the interaction between PD-L1 and programmed death 1 (PD-1) and subsequently preventing the suppression of T cells. In <i>in vivo</i> distribution experiments, CDEVs loaded with paclitaxel (PTX) demonstrated better tumor targeting capabilities. Remarkably, following CDEVs-PTX treatment, CD8+ T cell levels in mice were increased, presumably leading to improved antitumor effects. <b>Conclusion:</b> CDEVs not only serve as drug carriers but also function as drugs themselves; as such, through a single administration of CDEVs, it is possible to combine immunotherapy and chemotherapy to achieve better effects between the two, providing a more comprehensive and effective cancer treatment strategy that promises to improve treatment outcomes and reduce the adverse effects of therapy.</p>","PeriodicalId":520322,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"5 4","pages":"597-613"},"PeriodicalIF":0.0,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11725424/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142985686","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}
Katarzyna Kowalik, Kamila Kulig, Elzbieta Karnas, Olga Barczyk-Woznicka, Ewa Zuba-Surma, Elzbieta Pyza, Maria Rapala-Kozik, Justyna Karkowska-Kuleta
{"title":"Extracellular vesicles of <i>Lactiplantibacillus plantarum</i> PCM 2675 and <i>Lacticaseibacillus rhamnosus</i> PCM 489: an introductory characteristic.","authors":"Katarzyna Kowalik, Kamila Kulig, Elzbieta Karnas, Olga Barczyk-Woznicka, Ewa Zuba-Surma, Elzbieta Pyza, Maria Rapala-Kozik, Justyna Karkowska-Kuleta","doi":"10.20517/evcna.2024.49","DOIUrl":"10.20517/evcna.2024.49","url":null,"abstract":"<p><p><b>Aim:</b> Extracellular vesicles (EVs) are involved in intercellular and interkingdom communication in the complex communities that constitute the niche-specific microbiome of the colonized host. Therefore, studying the structure and content of EVs produced by resident bacteria is crucial to understanding their functionality and impact on the host and other microorganisms. <b>Methods:</b> Bacterial EVs were isolated by differential centrifugation, their size and concentration were measured by transmission electron microscopy and nanoparticle tracking analysis, and the cargo proteins were identified by liquid chromatography coupled to tandem mass spectrometry. The cytotoxicity of bacterial EVs was tested using the human epithelial cell line A549 and an <i>in vivo</i> model of <i>Galleria mellonella</i> larvae. <b>Results:</b> The isolation and preliminary characteristics of EVs from two strains of lactic acid bacteria - <i>Lactiplantibacillus plantarum</i> PCM 2675 and <i>Lacticaseibacillus rhamnosus</i> PCM 489 - were presented, confirming the production of vesicular structures with sizes in the range of 50-170 nm for <i>L. plantarum</i> and 80-250 nm for <i>L. rhamnosus</i>. In addition, various proteins were identified within EVs cargo, with distinct locations of origin, including membrane, cytoplasmic and extracellular proteins, and with diverse functions, including enzymes with confirmed proteolytic activity. Furthermore, bacterial EVs did not show statistically significant cytotoxicity to the host under the tested conditions. <b>Conclusions</b>: A better understanding of the composition and functionality of bacterial EVs may contribute to their future effective use in supporting human health.</p>","PeriodicalId":520322,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"5 4","pages":"580-596"},"PeriodicalIF":0.0,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11725429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142985596","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}
Hawa Ndiaye, Simran Rajput, John F K Sauld, Gautam Mahajan, Saumya Das, Emeli Chatterjee
{"title":"EV-idence uncovered: kidney-on-chip study links circulating EVs of cardiorenal syndrome to renal pathology.","authors":"Hawa Ndiaye, Simran Rajput, John F K Sauld, Gautam Mahajan, Saumya Das, Emeli Chatterjee","doi":"10.20517/evcna.2024.70","DOIUrl":"10.20517/evcna.2024.70","url":null,"abstract":"<p><p>The intertwined nature of cardiac and renal failure, where dysfunction in one organ predicts a poor outcome in the other, has long driven the interest in uncovering the exact molecular links between the two. Elucidating the mechanisms driving Cardiorenal Syndrome (CRS) will enable the development of targeted therapies that disrupt this detrimental cycle, potentially improving outcomes for patients. A recent study by Chatterjee <i>et al</i>. (JCI insight 2023) demonstrated the feasibility of utilizing a humanized microfluidic kidney-on-chip model to elucidate the role of circulating extracellular vesicles (EVs) in the development of CRS (type 1 and type 2) in heart failure (HF) patients. The study also identified and validated EV miRNAs that correlated with kidney function by targeting several genes involved in kidney damage pathways, including transforming growth factor- β (TGF-β) signaling. These findings suggest that plasma EVs from CRS patients induce harmful responses in renal cells by regulating key pathways, highlighting their role in both type 1 and type 2 CRS.</p>","PeriodicalId":520322,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"5 4","pages":"574-579"},"PeriodicalIF":0.0,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11725426/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142985635","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":"Plasma extracellular vesicle: a novel biomarker for neurodegenerative disease diagnosis.","authors":"Xinrui Zhao, Shenglin Huang","doi":"10.20517/evcna.2024.56","DOIUrl":"10.20517/evcna.2024.56","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) are membrane-bound structures that carry proteins, lipids, RNA, and DNA, playing key roles in cell communication and material transport. Recent research highlights their potential as disease biomarkers due to their stability in bodily fluids. This study explores using tau and TDP-43 proteins in plasma EVs as diagnostic biomarkers for frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Analyzing plasma EVs from clinical cohorts, the study found that the 3R/4R tau ratio and TDP-43 levels effectively differentiate between diagnostic groups with high accuracy. Notably, plasma EV biomarkers demonstrate higher diagnostic accuracy and stability compared to direct plasma testing, providing new insights and approaches for future research and clinical practice. Further research is needed to validate these biomarkers in diverse populations and to establish standardized protocols. Future studies should continue to explore the potential of EV biomarkers in a broader range of neurodegenerative diseases and delve deeper into the mechanisms of EV secretion and sorting to enhance their diagnostic utility.</p>","PeriodicalId":520322,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"5 3","pages":"569-573"},"PeriodicalIF":0.0,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11648489/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142857527","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}
Beatrice Senigagliesi, Otmar Geiss, Stefano Valente, Hendrik Vondracek, Nicola Cefarin, Giacomo Ceccone, Luigi Calzolai, Laura Ballerini, Pietro Parisse, Loredana Casalis
{"title":"Substrate stiffness modulates extracellular vesicles' release in a triple-negative breast cancer model.","authors":"Beatrice Senigagliesi, Otmar Geiss, Stefano Valente, Hendrik Vondracek, Nicola Cefarin, Giacomo Ceccone, Luigi Calzolai, Laura Ballerini, Pietro Parisse, Loredana Casalis","doi":"10.20517/evcna.2024.47","DOIUrl":"10.20517/evcna.2024.47","url":null,"abstract":"<p><strong>Aim: </strong>The microenvironment effect on the tumoral-derived Extracellular Vesicle release, which is of significant interest for biomedical applications, still represents a rather unexplored field. The aim of the present work is to investigate the interrelation between extracellular matrix (ECM) stiffness and the release of small EVs from cancer cells. Here, we focus on the interrelation between the ECM and small extracellular vesicles (sEVs), specifically investigating the unexplored aspect of the influence of ECM stiffness on the release of sEVs.</p><p><strong>Methods: </strong>We used a well-studied metastatic Triple-Negative Breast Cancer (TNBC) cell line, MDA-MB-231, as a model to study the release of sEVs by cells cultured on substrates of different stiffness. We have grown MDA-MB-231 cells on two collagen-coated polydimethylsiloxane (PDMS) substrates at different stiffness (0.2 and 3.6 MPa), comparing them with a hard glass substrate as control, and then we isolated the respective sEVs by differential ultracentrifugation. After checking the cell growth conditions [vitality, morphology by immunofluorescence microscopy, stiffness by atomic force microscopy (AFM)], we took advantage of a multi-parametric approach based on complementary techniques (AFM, Nanoparticle Tracking Analysis, and asymmetric flow field flow fractionation with a multi-angle light scattering detector) to characterize the TNBC-derived sEV obtained in the different substrate conditions.</p><p><strong>Results: </strong>We observe that soft substrates induce TNBC cell softening and rounding. This effect promotes the release of a high number of larger sEVs.</p><p><strong>Conclusion: </strong>Here, we show the role of ECM physical properties in the regulation of sEV release in a TNBC model. While the molecular mechanisms regulating this effect need further investigation, our report represents a step toward an improved understanding of ECM-cell-sEVs crosstalk.</p>","PeriodicalId":520322,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"5 3","pages":"553-568"},"PeriodicalIF":0.0,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11648499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142857529","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":"Hitting the target: cell signaling pathways modulation by extracellular vesicles.","authors":"Giada Cerrotti, Sandra Buratta, Raffaella Latella, Eleonora Calzoni, Gaia Cusumano, Agnese Bertoldi, Serena Porcellati, Carla Emiliani, Lorena Urbanelli","doi":"10.20517/evcna.2024.16","DOIUrl":"10.20517/evcna.2024.16","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) are lipid bilayer-enclosed nanoparticles released outside the cell. EVs have drawn attention not only for their role in cell waste disposal, but also as additional tools for cell-to-cell communication. Their complex contents include not only lipids, but also proteins, nucleic acids (RNA, DNA), and metabolites. A large part of these molecules are involved in mediating or influencing signal transduction in target cells. In multicellular organisms, EVs have been suggested to modulate signals in cells localized either in the neighboring tissue or in distant regions of the body by interacting with the cell surface or by entering the cells via endocytosis or membrane fusion. Most of the EV-modulated cell signaling pathways have drawn considerable attention because they affect morphogenetic signaling pathways, as well as pathways activated by cytokines and growth factors. Therefore, they are implicated in relevant biological processes, such as embryonic development, cancer initiation and spreading, tissue differentiation and repair, and immune response. Furthermore, it has recently emerged that multicellular organisms interact with and receive signals through EVs released by their microbiota as well as by edible plants. This review reports studies investigating EV-mediated signaling in target mammalian cells, with a focus on key pathways for organism development, organ homeostasis, cell differentiation and immune response.</p>","PeriodicalId":520322,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"5 3","pages":"527-552"},"PeriodicalIF":0.0,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11648414/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142857522","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}