Extracellular vesicles and circulating nucleic acids最新文献

{"title":"Inhalable exosomes to target cardiac repair.","authors":"Ajit Magadum","doi":"10.20517/evcna.2024.81","DOIUrl":"https://doi.org/10.20517/evcna.2024.81","url":null,"abstract":"<p><p>A recent study introduces Stem Cell-derived Exosome Nebulization Therapy (SCENT), a novel, non-invasive strategy that delivers lung spheroid cell-derived exosomes via inhalation to promote cardiac repair after myocardial infarction. This approach improves cardiac function, reduces injury, and demonstrates translational potential in both small and large animal models, offering a promising avenue for cell-free, inhalable regenerative therapies.</p>","PeriodicalId":520322,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"6 1","pages":"180-182"},"PeriodicalIF":0.0,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11977353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144059794","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":"A milestone for the therapeutic EV field: FDA approves Ryoncil, an allogeneic bone marrow-derived mesenchymal stromal cell therapy.","authors":"Bernd Giebel","doi":"10.20517/evcna.2025.02","DOIUrl":"https://doi.org/10.20517/evcna.2025.02","url":null,"abstract":"<p><p>Small extracellular vesicles (sEVs) derived from mesenchymal stromal cells (MSCs) hold substantial promise for therapeutic applications, including immune modulation and tissue regeneration. However, challenges such as batch-to-batch variability, donor material diversity, and the lack of standardized potency testing remain significant barriers to clinical translation. The recent U.S. Food and Drug Administration (FDA) approval of Ryoncil (remestemcel-L) for steroid-refractory acute graft-versus-host disease (aGvHD) in pediatric patients represents a crucial milestone for MSC-based therapies, offering also valuable insights for the development of MSC-EV therapies. This approval highlights the critical need to address variability and standardization issues in MSC products. Strategies like immortalizing MSCs and expanding them clonally can improve scalability, consistency, and overcome limitations inherent to cellular MSC therapies. With the FDA's decision signaling significant progress, optimizing MSC expansion protocols and refining potency testing methods will be crucial for advancing MSC-EVs as a viable therapeutic option, overcoming current challenges, and expanding clinical applications.</p>","PeriodicalId":520322,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"6 1","pages":"183-190"},"PeriodicalIF":0.0,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11977348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144050047","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":"Unraveling the role of amphisomes in mast cell secretory granule fusion and exosome release.","authors":"Irene Tsilioni","doi":"10.20517/evcna.2024.96","DOIUrl":"https://doi.org/10.20517/evcna.2024.96","url":null,"abstract":"<p><p>Mast cells (MCs) play a crucial role in immune responses by storing and releasing inflammatory mediators from secretory granules (SGs). The biogenesis, maturation, and fusion of these granules with the plasma membrane regulate inflammation, immune cell recruitment, and tissue homeostasis. However, the exact mechanism underlying this process remains unclear. Recent studies have identified a novel mechanism of SG fusion involving amphisomes, hybrid organelles formed by the fusion of late endosomes and autophagosomes. This process not only facilitates SG enlargement but also promotes the release of exosomes, small vesicles crucial for intercellular communication and immune modulation. In particular, Omari <i>et al.</i> delve into the molecular machinery governing amphisome formation and SG fusion, focusing on key players such as Rab5, PTPN9, CD63, and phosphoinositides (PIs). They propose a dynamic model wherein amphisomes act as intermediates in SG maturation, promoting homotypic fusion events that regulate SG content and size. A critical aspect of this process is the lipid signaling cascade, particularly involving PI4K and CD63, which coordinates SG fusion and exosome release. These findings challenge the conventional view of SGs as static storage compartments, positioning them as dynamic hubs of vesicle trafficking and secretion. By elucidating the role of amphisomes and lipid signaling in SG biology, this study offers a significant shift in understanding and introduces new concepts that could drive future research. This commentary, while endorsing the authors' key conclusions, also highlights important questions regarding the functional implications of these novel mechanisms and their potential therapeutic applications.</p>","PeriodicalId":520322,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"6 1","pages":"176-179"},"PeriodicalIF":0.0,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11977352/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144032406","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":"Sustained release of cytokines from migrasomes.","authors":"Yan Zhen, Harald Stenmark","doi":"10.20517/evcna.2025.15","DOIUrl":"https://doi.org/10.20517/evcna.2025.15","url":null,"abstract":"<p><p>Cytokines are released by cells in response to infections and tissue damage. A recent paper by Jiao <i>et al</i>. demonstrates that circulating monocytes release the cytokines tumor necrosis factor and Interleukin-6 encapsulated in large extracellular vesicles called migrasomes, from which the cytokines are secreted locally in a sustained fashion.</p>","PeriodicalId":520322,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"6 1","pages":"171-175"},"PeriodicalIF":0.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11977381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144061276","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":"CD63, a new therapeutical candidate for cholesterol homeostasis regulation through extracellular vesicles?","authors":"Julien Saint-Pol, Laurence Fenart","doi":"10.20517/evcna.2024.92","DOIUrl":"https://doi.org/10.20517/evcna.2024.92","url":null,"abstract":"<p><p>CD63 is a tetraspanin initially associated with late endosomes and contributes to numerous functions at the cell level, such as intracellular endosomal and lysosomal trafficking, adhesion, and motility. CD63 also plays a key role in the biogenesis and release of exosomes, i.e., small extracellular vesicles (EVs) of endosomal origin, facilitating the formation of multivesicular bodies (MVBs), the coordination with the endosomal sorting complexes required for transport (ESCRT) machinery, the selection of cargoes carried by future exosomes, and the fusion of MVBs with the plasma membrane for exosome release. In a recent publication in <i>Nature Cell Biology</i>, Guillaume van Niel's team provides arguments in favor of another EV-linked function for CD63, namely the regulation of cholesterol storage and release by small EVs of endogenous origin. Complemented by two other publications from the teams of Keisuke Ito and Xabier Ostreikoetxea, which respectively describe the role of (i) mitochondrial metabolism on CD63 function and (ii) the link between the reduced CD63⁺ small EVs and dyslipidemia, these arguments highlight the key role of CD63 in the regulation of cholesterol homeostasis through exosomes and more widely small EVs in physiological and pathological conditions. Future research on CD63 may thus redefine our approach to cellular lipid management and therapeutic lipid delivery.</p>","PeriodicalId":520322,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"6 1","pages":"166-170"},"PeriodicalIF":0.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11977374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144059750","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":"Gas-powered extracellular vesicles promote bone regeneration.","authors":"Lexie Shannon Holliday, John K Neubert, Xianrui Yang","doi":"10.20517/evcna.2024.91","DOIUrl":"https://doi.org/10.20517/evcna.2024.91","url":null,"abstract":"<p><p>The signaling gas hydrogen sulfide (H₂S) has recently been implicated in the regulation of bone remodeling and the maintenance of periodontal health. Exploring the underlying mechanisms for this regulation holds promise for the development of new treatment strategies to block bone resorption and stimulate bone regeneration. A recent study by Zhou <i>et al.</i> (Bioactive Materials, 2024) showed that treatment with H₂S stimulated changes in the extracellular vesicles (EVs) released by M2 macrophages, enhancing their capacity to promote the osteogenic differentiation of mesenchymal stem cells <i>in vitro.</i> The H₂S-stimulated EVs, given together with mesenchymal stem cells (MSCs), also promoted bone regeneration <i>in vivo</i> in a mouse calvarial critical-size defect model. This activity was linked to augmented expression of moesin, a membrane-cytoskeletal linkage protein, which was found at increased levels in EVs from cells stimulated by H₂S. The study identifies a new strategy for generating EVs that are pro-osteogenic. It also uncovers a surprising role for moesin in stimulating osteogenesis in MSCs.</p>","PeriodicalId":520322,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"6 1","pages":"158-165"},"PeriodicalIF":0.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11977345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144059572","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":"Impact of exosomes derived from adipose stem cells on lymphocyte proliferation and phenotype in mouse skin grafts.","authors":"Xinqiang Li, Xueteng Wang, Hailun Cai, Ye Wang, Xin Zhou, Bin Wu, Jinzhen Cai, Dahong Teng","doi":"10.20517/evcna.2024.52","DOIUrl":"https://doi.org/10.20517/evcna.2024.52","url":null,"abstract":"&lt;p&gt;&lt;p&gt;&lt;b&gt;Aim:&lt;/b&gt; Exosomes derived from adipose-derived stem cells (ASCs) in mice have been reported to influence immune regulation. Yet, the potential immunological effects of ASCs-derived exosomes and their interaction with lymphocytes during transplant immunity remain understudied. &lt;b&gt;Methods:&lt;/b&gt; ASCs from BALB/c mice, along with their conditioned culture medium, were collected for the extraction, isolation, and comprehensive characterization of exosomes. Splenic cell suspensions were isolated from BALB/c mice and subsequently processed for downstream analyses. Lymphocytes were isolated via gradient centrifugation and stimulated &lt;i&gt;in vitro&lt;/i&gt; with the purified exosomes to assess their functional responses. Lymphocyte proliferation was quantified using the CCK8 assay, and the relative frequencies of CD4+ T cells, CD8+ T cells, Treg cells, NK (natural killer) cells, macrophages, B cells, dendritic cells (DCs), and Th17 cells were determined through flow cytometric analysis. Before establishing the skin transplantation model, the mice were administered PBS, 0.5 × 10&lt;sup&gt;8&lt;/sup&gt; exosomes, 1 × 10&lt;sup&gt;8&lt;/sup&gt; exosomes, 1.5 × 10&lt;sup&gt;8&lt;/sup&gt; exosomes, or ASCs via intravenous injection through the tail vein. Seven days after transplantation, the spleens, drainage lymph nodes, and blood samples were harvested for lymphocyte isolation and further downstream analyses. &lt;b&gt;Results:&lt;/b&gt; Exosomes derived from ASCs significantly increased the CD4+/CD8+ ratio and Treg cell levels, without inducing any notable changes in Th17 cell content or CTLA-4 protein expression in CD4+ T cells. Compared to the PBS-treated group, both ASC and exosome treatment groups demonstrated an enhanced CD4+/CD8+ ratio, increased Treg cell content, and elevated CTLA-4 protein expression in spleen tissue following skin transplantation, while Th17 cell levels remained unaffected. Compared to the ASC treatment group, the exosome group exhibited a higher CD4+/CD8+ ratio and Treg cell levels, alongside a reduced proportion of PD-1+ Treg cells and lower CTLA-4 protein expression in CD3+CD4+ T cells. No significant differences were observed in the proportions of NK cells, macrophages, B cells, and DCs in the spleens across all treatment groups. In peripheral blood, an increased proportion of CD3+ T cells, macrophages, and DCs was detected, accompanied by a reduced proportion of NK cells and B cells. In the draining lymph nodes, no significant changes were observed in the proportions of CD3+ T cells and B cells, while macrophages, NK cells, and DCs showed elevated proportions. In the exosome-treated group, mouse grafts exhibited a disorganized and thinner granular layer, accompanied by focal regions of inflammatory cell infiltration. Both exosome and ASC treatments significantly extended the survival of skin grafts. &lt;b&gt;Conclusion:&lt;/b&gt; Exosomes derived from ASCs promote lymphocyte proliferation and modulate their phenotypic profiles in mouse skin graft models, effectively extending graft sur","PeriodicalId":520322,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"6 1","pages":"141-157"},"PeriodicalIF":0.0,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11977351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143998393","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":"The times they are AI-changing: AI-powered advances in the application of extracellular vesicles to liquid biopsy in breast cancer.","authors":"Vanesa García-Barberán, María Elena Gómez Del Pulgar, Heidy M Guamán, Alberto Benito-Martin","doi":"10.20517/evcna.2024.51","DOIUrl":"https://doi.org/10.20517/evcna.2024.51","url":null,"abstract":"<p><p>Artificial intelligence (AI) is revolutionizing scientific research by facilitating a paradigm shift in data analysis and discovery. This transformation is characterized by a fundamental change in scientific methods and concepts due to AI's ability to process vast datasets with unprecedented speed and accuracy. In breast cancer research, AI aids in early detection, prognosis, and personalized treatment strategies. Liquid biopsy, a noninvasive tool for detecting circulating tumor traits, could ideally benefit from AI's analytical capabilities, enhancing the detection of minimal residual disease and improving treatment monitoring. Extracellular vesicles (EVs), which are key elements in cell communication and cancer progression, could be analyzed with AI to identify disease-specific biomarkers. AI combined with EV analysis promises an enhancement in diagnosis precision, aiding in early detection and treatment monitoring. Studies show that AI can differentiate cancer types and predict drug efficacy, exemplifying its potential in personalized medicine. Overall, the integration of AI in biomedical research and clinical practice promises significant changes and advancements in diagnostics, personalized medicine-based approaches, and our understanding of complex diseases like cancer.</p>","PeriodicalId":520322,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"6 1","pages":"128-140"},"PeriodicalIF":0.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11977355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144004028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular vesicle-mediated chemoresistance in breast cancer: focus on miRNA cargo.","authors":"Maria Chiara Ciferri, Roberta Tasso","doi":"10.20517/evcna.2024.90","DOIUrl":"https://doi.org/10.20517/evcna.2024.90","url":null,"abstract":"<p><p>The role of extracellular vesicles (EVs) in mediating chemoresistance has gained significant attention due to their ability to transfer bioactive molecules between drug-resistant and drug-sensitive cells. In particular, they have been demonstrated to play an active part in breast cancer chemoresistance by the horizontal transfer of genetic and protein material. This review highlights the role of EVs, particularly their miRNA cargo, in driving drug resistance in breast cancer. EVs derived from chemoresistant cells carry miRNAs and lncRNAs, which are known to modulate gene networks involved in cell proliferation and survival. These cargo molecules suppress apoptosis by targeting pro-apoptotic genes like PTEN and BIM, promote epithelial-mesenchymal transition (EMT) through the regulation of pathways such as TGF-β and Wnt/b-catenin, and contribute to tumor growth and resistance by enhancing angiogenesis and modulating the tumor microenvironment. Beyond RNA-mediated effects, EVs also transfer functional proteins, including P-glycoprotein and Hsp70, which impact cellular metabolism and survival pathways. Our findings underscore the significance of EVs in breast cancer chemoresistance, suggesting their potential involvement as possible prognostic factors to predict therapy response and as therapeutic targets in combination with usual therapy.</p>","PeriodicalId":520322,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"6 1","pages":"112-127"},"PeriodicalIF":0.0,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11977373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144035112","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":"IFNγ preconditioning improves neuroprotection of MSC-derived vesicles on injured retinal ganglion cells by suppressing microglia activation via miRNA-dependent ribosome activity.","authors":"Tianjing You, Yuanxing Yang, Luodan A, Xuan Cheng, Xi Lin, Qingle Liang, Lingling Ge, Jing Xie, Siyu Chen, Na Liu, Juncai He, Haiwei Xu, Xiang Ma","doi":"10.20517/evcna.2024.66","DOIUrl":"https://doi.org/10.20517/evcna.2024.66","url":null,"abstract":"<p><p><b>Aim:</b> Microglial activation plays a pivotal role in the pathogenesis of retinal ganglion cell (RGC) degeneration resulting from optic nerve crush (ONC). Small extracellular vesicles (sEVs) secreted by mesenchymal stem cells (MSCs) have the potential to prevent retinal degeneration by modulating microglial activation. In this study, we elucidated the specific effects of sEVs derived from IFN-γ-primed MSCs on the phenotypic transition of microglia and the associated pathways in ONC mice. <b>Methods:</b> The ONC mice model was established and administered intravitreal injection with the sEVs derived from native MSCs (native sEVs) and the sEVs derived from MSCs primed with IFN-γ (IFNγ-sEVs). Their respective effects on the survival of the retinal ganglion cells (RGCs) and the transition of microglia phenotypes were determined through visual function testing and immunohistochemical staining. Combined with mRNA seq and microRNA seq techniques, we elucidated the mechanism of modulation of microglia phenotypic transformation by sEVs derived from MSCs primed by IFNγ. <b>Results:</b> It demonstrated that IFNγ-sEVs exhibited superior protective effects against RGC loss and reduced inflammatory responses in the ONC retina compared to native sEVs. Both types of sEVs promoted microglia activation to disease-associated microglia (DAM) phenotype, while IFNγ-sEVs especially suppressed interferon-responsive microglia (IRM) activation during RGCs degeneration. Subsequent miRNA sequencing suggested that <i>miR-423-5p</i>, which exhibited the most significant differential expression between the two sEVs types and elevated expression in IFNγ-sEVs, inhibited the expression of IRM and ribosomal genes. <b>Conclusion:</b> These findings suggest that IFN-γ-preconditioned MSCs may enhance sEVs of neuroprotection on RGCs by suppressing IRM activation through the secretion of sEVs containing specific microRNAs in ONC mice.</p>","PeriodicalId":520322,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"6 1","pages":"87-111"},"PeriodicalIF":0.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11977360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144059793","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}