Extracellular vesicles and circulating nucleic acids最新文献

{"title":"From gains to liver pain: when exercise training goes too far.","authors":"Benjamin I Burke, John J McCarthy, Ahmed Ismaeel","doi":"10.20517/evcna.2025.36","DOIUrl":"10.20517/evcna.2025.36","url":null,"abstract":"<p><p>A recent study from Liu <i>et al.</i> described the role of skeletal muscle-derived extracellular vesicles in promoting liver fibrosis as an outcome of chronic overtraining in mice. Here, we highlight this work and discuss its implications within the fields of exercise physiology and inter-organ communication.</p>","PeriodicalId":520322,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"6 2","pages":"324-327"},"PeriodicalIF":4.8,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12367453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144985815","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":"Optimized size exclusion chromatography demonstrates that extracellular vesicles are the key RNA carriers of ALK translocations in non-small cell lung cancer cell line secretome and patient plasma.","authors":"Beatriz Benayas, Estela Sánchez-Herrero, Lucía Robado de Lope, Joaquín Morales, Soraya López-Martín, Mariano Provencio, Mar Valés-Gómez, Atocha Romero, María Yáñez-Mó","doi":"10.20517/evcna.2025.14","DOIUrl":"10.20517/evcna.2025.14","url":null,"abstract":"<p><p><b>Aim:</b> Identification of <i>ALK</i> fusions in non-small cell lung cancer (NSCLC) is key to determining eligibility for treatment with ALK inhibitors that markedly improve patients' quality of life and survival outcomes. Circulating RNA, associated with various carriers including extracellular vesicles (EVs), lipoproteins (LPPs), or protein complexes, presents a viable target for the identification of ALK fusions by liquid biopsy. Our aim was to characterize the specific carrier of <i>ALK</i> fusion RNA, a crucial step in the development of diagnostic methods for clinical use. <b>Methods:</b> We employed optimized size-exclusion chromatography (SEC) to separate EVs, LPPs, and protein-enriched fractions from <i>ALK</i>-positive NSCLC cell lines and from pools of plasma obtained from NSCLC patients with <i>ALK</i> translocations. We optimized RNA fusion transcript detection using digital PCR (dPCR). <b>Results:</b> Protein analyses confirmed the successful resolution of EVs, LPPs, and protein fractions by optimized SEC. Our dPCR results indicated that <i>ALK</i> fusions were more prevalent in tetraspanin-enriched SEC fractions from NSCLC cell lines, suggesting that EVs serve as the primary carrier for <i>ALK</i> fusion RNA. After optimization for larger volumes of samples of the RNA isolation protocol, we could also demonstrate that <i>ALK</i> fusion transcripts were found exclusively in EVs from patient plasma. Of note, the circulating number of copies of the transcript was below 5 copies/mL. <b>Discussion:</b> Our findings underscore the potential of EV-associated RNA as a promising source for detecting <i>ALK</i> fusion variants in plasma samples from NSCLC patients, offering a non-invasive diagnostic approach with significant clinical implications.</p>","PeriodicalId":520322,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"6 2","pages":"310-323"},"PeriodicalIF":4.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12367459/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144985775","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":"Therapeutic potential of extracellular vesicles for treating human pregnancy disorders.","authors":"Shixuan Zheng, Harry M Georgiou, Maria I Kokkinos, Katrina M Mirabito Colafella, Shaun P Brennecke, Bill Kalionis","doi":"10.20517/evcna.2025.07","DOIUrl":"10.20517/evcna.2025.07","url":null,"abstract":"<p><p>Pregnancy complications such as preeclampsia and fetal growth restriction are major global health concerns, contributing to significant maternal and fetal morbidity and mortality. These disorders also increase the long-term risk of cardiovascular, metabolic, and kidney diseases in both mother and child. Accumulating evidence highlights the important role of placental mesenchymal stromal cell (MSC)-derived extracellular vesicles (EVs) in both healthy and pathological pregnancies. In healthy pregnancies, EVs support placental development and maternal-fetal communication. In contrast, EVs from diseased placentas can contribute to pregnancy complications. Importantly, EVs from healthy placental MSCs show promise as novel, cell-free therapies. They offer advantages over whole-cell therapies, including lower immunogenicity, no risk of replication, and easier storage and delivery. This review explores the role of placental MSC-derived EVs in pregnancy disorders, preeclampsia, fetal growth restriction, preterm birth, and gestational diabetes, and discusses their potential as targeted therapeutics. It also examines the future of bioengineered EVs and the challenges that must be addressed to bring EV-based therapies into clinical practice.</p>","PeriodicalId":520322,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"6 2","pages":"287-309"},"PeriodicalIF":4.8,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12367462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144985732","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":"Bovine milk extracellular vesicles prepared by ultracentrifugation contain microbial mRNAs that do not accumulate in human plasma following milk consumption.","authors":"Peerzada T Mumtaz, Bijaya Upadhyaya, Jiang Shu, Juan Cui, Janos Zempleni","doi":"10.20517/evcna.2024.84","DOIUrl":"10.20517/evcna.2024.84","url":null,"abstract":"<p><p><b>Aim:</b>Small extracellular vesicles (sEVs) and their RNA cargo are not exclusively derived from endogenous synthesis but can also be absorbed from milk and gut bacteria. Given the high rate of bacterial fermentation in the gastrointestinal tract of ruminants, we hypothesized that preparations of bovine milk sEVs (BMEs) contain bacterial mRNAs whose bioavailability in humans remains unknown. <b>Methods:</b> BMEs were purified from chilled antibiotics-treated raw milk (RM) and store-bought skim milk (SBM) using sequential ultracentrifugation. BMEs from RM were treated with RNase to remove RNA adsorbed to the BME surface. BMEs from SBM were treated (SBM+) or not treated (SBM-) with RNase. mRNAs were identified by RNA sequencing analysis and mapping to the bovine genome and bacterial reference. The bioavailability of bacterial mRNA was assessed by RNA sequencing analysis of plasma collected before and 4 h after consuming one liter of cow's milk in humans. <b>Results:</b> Approximately 50% of the mRNA sequencing reads were non-bovine in BMEs from RM, SBM+, and BM-. Up to two-thirds of the non-bovine contigs mapped to microbial transcriptomes, including bacteria, viruses, and fungi. The levels of 17 bacterial mRNAs from <i>Escherichia coli</i> and <i>Cutibacterium acnes</i> were significantly higher after milk consumption compared to before milk consumption, but the number of reads was too low to confidently draw the conclusion that microbial mRNAs in milk are bioavailable in humans. <b>Conclusions:</b> BMEs prepared by ultracentrifugation contain bacterial mRNAs that are not bioavailable in humans.</p>","PeriodicalId":520322,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"6 2","pages":"276-286"},"PeriodicalIF":4.8,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12367460/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144985817","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":"Small extracellular vesicles, their cargo, and oxidative stress: emerging biomarkers for glaucoma diagnosis and treatment.","authors":"Francisco J Romero, Manuel Diaz-Llopis","doi":"10.20517/evcna.2025.22","DOIUrl":"10.20517/evcna.2025.22","url":null,"abstract":"<p><p>The contribution commented on is a relevant bridging work between extracellular vesicles, oxidative stress, and proteomics (especially regarding biomarkers) research. The findings reported are promising but further point out one of the future directions for investigations in glaucoma and certainly other such complex diseases.</p>","PeriodicalId":520322,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"6 2","pages":"272-275"},"PeriodicalIF":4.8,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12367457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144985819","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 role of plant extracellular vesicles in cell wall remodeling.","authors":"Carine de Marcos Lousa","doi":"10.20517/evcna.2025.17","DOIUrl":"10.20517/evcna.2025.17","url":null,"abstract":"<p><p>Lignin is an important component of plant cell walls, providing structural support and defense. Despite extensive research, the mechanisms underlying the transport and polymerization of lignin precursors remain poorly understood. Kankaanpää <i>et al</i>. have explored the role of extracellular vesicles (EVs) in lignin biosynthesis in <i>Picea abies</i> (Norway spruce). The authors identify key metabolites and enzymes involved in lignin biosynthesis and polymerization enriched in EVs from suspension cultures, suggesting a direct role for EVs in the transport and polymerization of lignin precursors. In addition, the presence of salicylic acid (SA) in EVs also highlights a novel synergy between lignin biosynthesis and plant defense mechanisms. This discovery challenges the traditional understanding of lignin biosynthesis by proposing that EVs act as mobile carriers, facilitating the localized polymerization of lignin in the cell wall. Further research is still needed to elucidate the exact nature of the EVs involved and the mechanisms of loading into and release from EVs. Nevertheless, these findings offer novel insights into the regulation of lignin biosynthesis and may have larger implications for agriculture and industrial applications.</p>","PeriodicalId":520322,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"6 2","pages":"267-271"},"PeriodicalIF":4.8,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12367456/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144985742","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":"Tumor microenvironment: new era in exosomal circRNA research - a bibliometric analysis.","authors":"Hai-Quan Wang, Lu Zhang, Ming-Jie Li, Rong-Quan He, Di-Yuan Qin, Bin Li, Jian-Di Li, Ke-Jun Wu, Shi-De Li, Han He, Zhen-Bo Feng, Gang Chen","doi":"10.20517/evcna.2024.102","DOIUrl":"10.20517/evcna.2024.102","url":null,"abstract":"<p><p><b>Aim:</b> The domain of exosomal circRNAs has seen rapid growth over the past few years, yet a thorough synthesis of the scholarly contributions has been lacking. This study employs bibliometric analysis to uncover the focal points and trends in exosomal circRNA research. <b>Methods:</b> We selected articles on exosomal circRNAs from the Web of Science Core Collection (WoSCC) and deployed VOSviewer for co-authorship and co-occurrence analysis. CiteSpace was tapped to calculate citation bursts for documents and keywords, generating a time-zone map. Additionally, the bibliometrix R package was employed to identify locally cited references and construct thematic maps and trend topics. <b>Results:</b> The exosomal circRNA research field has produced 767 articles over the past decade. China and Fudan University lead in publication counts, ranking first among countries and institutions, respectively. The journal with the highest number of publications and citations is <i>Molecular Cancer</i>. Zhang Wei and Li Yan are the top contributors and the most co-cited authors, respectively. Analysis of the results suggests that research related to the tumor microenvironment (TAM) may be a recent research hotspot. Among the latest keywords, terms such as microenvironment, macrophage, mesenchymal stem cells, and ceRNA appear frequently. The keyword with the most recent citation burst is ceRNA. The latest trend topic is the macrophage, and mesenchymal stem cell is identified as an emerging theme. <b>Conclusion:</b> This study elucidates the hotspots and trends in exosomal circRNA research through bibliometric analysis. Themes related to the TAM, especially directions involving macrophages, fibroblasts, and mesenchymal stem cells, will likely open a new chapter in exosomal circRNA research.</p>","PeriodicalId":520322,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"6 2","pages":"245-266"},"PeriodicalIF":4.8,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12367469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144985752","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 vesicles: emerging therapeutic agents for liver fibrosis.","authors":"Giulia Chiabotto, Armina Semnani, Elena Ceccotti, Stefania Bruno","doi":"10.20517/evcna.2025.08","DOIUrl":"10.20517/evcna.2025.08","url":null,"abstract":"<p><p>Liver fibrosis is a progressive condition characterized by excessive scar tissue buildup, leading to impaired liver function and potentially cirrhosis. Despite advancements in treatment strategies, effective anti-fibrotic therapies remain an urgent unmet need. Recent research has identified extracellular vesicles (EVs) as promising therapeutic agents due to their ability to mediate intercellular communication and regulate key fibrotic pathways. This review aims to provide a comprehensive overview of the therapeutic potential of EVs in different <i>in vitro</i> and <i>in vivo</i> models of hepatic fibrosis, focusing on their natural effects and recent advancements in their engineering for enhanced efficacy. EVs can be derived from various cellular sources, including mesenchymal stromal cells (MSCs) and liver-resident cells. Biological materials, including serum, breast milk, bacteria, and plants, also serve as EV sources. Among these, MSC-EVs stand out for their therapeutic potential, which can be significantly enhanced through preconditioning with inflammatory signals, pharmacological agents, or genetic engineering to improve EV quality and efficacy. Engineering techniques have further expanded EV applications, enabling their use as precise and effective drug-delivery vehicles. Approaches such as loading EVs with pharmacological compounds, designing customized EVs, and creating EV-liposome hybrids enable targeted delivery to activated hepatic stellate cells (HSCs), central drivers of fibrosis progression. These strategies enhance the efficacy of EV-based treatments. Both natural and engineered EVs regulate critical pathways of liver fibrosis development, including activation of HSCs, modulation of pro-fibrotic genes, extracellular matrix deposition, and programmed cell death. Additionally, EVs modulate immune responses, fostering a liver microenvironment conducive to repair and regeneration. Combining the natural regenerative properties of EVs with innovative engineering strategies provides highly targeted, effective treatment approaches to restore liver function and address the urgent unmet need for chronic liver disease therapies.</p>","PeriodicalId":520322,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"6 2","pages":"216-244"},"PeriodicalIF":4.8,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12367467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144985757","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":"Secretome and extracellular vesicle signatures in bone marrow-derived mesenchymal stromal cells after expansion in standard and next-generation media.","authors":"Giulio Grieco, Simona Piccolo, Enrico Ragni, Laura de Girolamo","doi":"10.20517/evcna.2024.99","DOIUrl":"10.20517/evcna.2024.99","url":null,"abstract":"<p><p><b>Aim:</b> Mesenchymal stem cells (MSCs) are a promising therapeutic strategy for osteoarthritis (OA), largely due to their regenerative potential, which is attributed in part to their secretome. The secretome includes soluble factors and extracellular vesicles (EVs). Given that MSCs are sensitive to various culture conditions, this study aims to investigate the effects of different media supplemented with either fetal bovine serum (FBS) (F), platelet lysate (P), or serum/xeno-free (S/X) on the composition and therapeutic potential of the secretome from bone marrow-derived MSCs (BMSCs). <b>Methods:</b> BMSCs were cultured in F, P, or S/X media, with secretomes collected after starvation. The secretomes were analyzed for soluble factors, EVs, and miRNAs. Inflammatory responses were assessed in an <i>in vitro</i> OA model using inflamed chondrocytes and gene expression was evaluated by qRT-PCR. <b>Results:</b> The secretomes from all conditions exhibited a similar molecular fingerprint. Proteomic analysis identified 98 common proteins encompassing growth factors and inflammatory mediators. EVs showed similar size and phenotype, with a slight difference in CD44 expression in EVs derived from P-expanded MSCs. Despite the high overall similarity, miRNA profiling identified 13 key players, with subtle differences in the miRNA composition of EVs from FBS-expanded BMSCs. All secretomes exhibited anti-inflammatory effects, with the FBS-expanded secretome showing the most pronounced therapeutic potential. <b>Conclusion:</b> The secretomes derived from different culture conditions share key molecular components. EVs may contribute to variations in therapeutic outcomes through their cargo. Optimizing MSC expansion conditions is crucial for enhancing the therapeutic potential of MSC-derived secretomes in OA treatment. Further research is needed to clarify the specific role of factors, miRNAs, and EVs in modulating OA pathology.</p>","PeriodicalId":520322,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"6 2","pages":"195-215"},"PeriodicalIF":4.8,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12367461/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144985810","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":"Exosomal miR-302b as a novel strategy for reversing cellular senescence and promoting healthy aging.","authors":"Consuelo Borrás","doi":"10.20517/evcna.2025.24","DOIUrl":"10.20517/evcna.2025.24","url":null,"abstract":"<p><p>The study by Bi <i>et al</i>. (2025) presents \"Senoreverse\", an innovative strategy that utilizes exosomal miR-302b to restore the proliferative capacity of senescent cells (SnCs), thus extending lifespan and enhancing cognitive and physical function in aging mice without the risk of tumorigenicity.</p>","PeriodicalId":520322,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"6 2","pages":"191-194"},"PeriodicalIF":4.8,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12367455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144985749","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}