Extracellular vesiclePub Date : 2025-12-01Epub Date: 2025-08-26DOI: 10.1016/j.vesic.2025.100093
Zachary F. Greenberg , Regina Oshins , Karina Serban , Sina F. Bazargani , Timothy J. Garrett , Nancy G. Casanova , Joe GN. Garcia , Mei He , Nazli Khodayari
{"title":"Neutrophil-derived extracellular vesicles in the plasma of alpha-1 antitrypsin deficient individuals reveal pro-inflammatory metabolic and transcriptomic signatures","authors":"Zachary F. Greenberg , Regina Oshins , Karina Serban , Sina F. Bazargani , Timothy J. Garrett , Nancy G. Casanova , Joe GN. Garcia , Mei He , Nazli Khodayari","doi":"10.1016/j.vesic.2025.100093","DOIUrl":"10.1016/j.vesic.2025.100093","url":null,"abstract":"<div><div>Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder caused by mutations in <em>SERPINA1</em>, leading to chronic obstructive pulmonary disease (COPD) and liver disease. Neutrophils are key regulators of inflammatory signaling networks; however, their dysregulation in AATD and the underlying molecular mechanisms remain poorly understood. Here, we employed a multi-omics approach integrating RNA sequencing (RNA-seq) and metabolomics to comprehensively characterize neutrophil dysfunction in AATD. RNA-seq analysis of blood neutrophils from AATD individuals revealed transcriptional dysregulation in genes involved in intracellular signaling, immune response regulation, and metabolic adaptation. Isolation and characterization of neutrophil-derived extracellular vesicles (EV) demonstrated an increased plasma burden of neutrophil elastase (NE)-rich EV with elevated surface-bound NE. Metabolomic profiling revealed that these EVs are enriched with pro-inflammatory metabolites linked to dysregulated signaling pathways. Integrated transcriptomic and metabolomic network analysis showed that altered neutrophil gene expression and signaling pathways reshape EV metabolic cargo, linking metabolic reprogramming to inflammatory signal transduction in AATD. Furthermore, differentially expressed EV metabolites may modulate gene expression in recipient cells, sustaining chronic inflammation in AATD. The observed upregulation of interferon, pattern recognition receptors, and cytokine-mediated signaling pathways in neutrophils suggests a potential feedback loop amplifying inflammation in AATD and COPD.</div></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"6 ","pages":"Article 100093"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144903149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Extracellular vesiclePub Date : 2025-12-01Epub Date: 2025-07-10DOI: 10.1016/j.vesic.2025.100087
Qi Wu , Fanxiu Ma , Meng Yuan , Xiumei Jin , Zhaodi Jiang , Jiyan Ma
{"title":"Novel mouse models for tracing brain-derived extracellular vesicles","authors":"Qi Wu , Fanxiu Ma , Meng Yuan , Xiumei Jin , Zhaodi Jiang , Jiyan Ma","doi":"10.1016/j.vesic.2025.100087","DOIUrl":"10.1016/j.vesic.2025.100087","url":null,"abstract":"<div><div>Extracellular vesicles (EVs), particularly small extracellular vesicles (sEVs) such as exosomes, are carriers of biomolecules that reflect the metabolic status of host cells. Recently, sEVs have emerged as potential reservoirs of molecular biomarkers associated with pathological conditions, including cancers, neurodegenerative disorders, and cardiovascular diseases. While blood-based tests are common diagnostic tools, their efficacy in identifying central nervous system (CNS) diseases is significantly hindered by the blood-brain barrier, which prevents the entry of brain-derived proteins into the bloodstream. Capturing brain-derived sEVs (BDEs) in peripheral blood is a potential alternative for detecting CNS disease biomarkers. However, the presence of BDEs in blood remains obscure due to the lack of specific labeling. To address this challenge, we established two novel mouse models in which neuron-derived sEVs or EVs from specific brain regions were fluorescently labeled. Using these approaches we successfully detected fluorescently labeled EVs in both BDEs and plasma-derived sEVs (PDEs), confirming that BDEs are indeed present in peripheral blood. These models will serve as valuable tools for developing novel methods to efficiently capture BDEs in peripheral blood.</div></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"6 ","pages":"Article 100087"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144588905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The mechanisms and application prospects of exosomes in acute myocardial infarction","authors":"Peng Zhou , Jia Zhang , Leilei Zhang , Jiangwei Yan , Chen Fang","doi":"10.1016/j.vesic.2025.100073","DOIUrl":"10.1016/j.vesic.2025.100073","url":null,"abstract":"<div><div>Acute myocardial infarction (AMI) is a significant cause of death in cardiovascular diseases and an important topic in forensic pathology. It triggers various cellular pathological changes, leading to ventricular remodeling, changes in cardiac function, and, in severe cases, death. Current biomarkers for AMI lack specificity and can be influenced by various factors, making them challenging for diagnosis and differentiation. Exosomes, small vesicles with a lipid bilayer membrane, have emerged as potential biomarkers and therapeutic targets for AMI. They play a crucial role in intercellular cargo transport and communication. Exosomes play a dual role in cellular processes, exhibiting protective mechanisms under normal conditions while also contributing to disease progression in pathological contexts. This paper summarizes the mechanisms, research strategies, and application prospects of exosomes in AMI, providing insights for forensic investigations.</div></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"5 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143776595","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":"Exofection by exosomes: A transient functional cargo transfer","authors":"Ramkumar Menon, Madhuri Tatiparthy, Jessica Selim, Isidore Mushimiyimana, Brinley Harrington, Awanit Kumar, Lauren Richardson, Emmanuel Amabebe, Ananth Kumar Kammala","doi":"10.1016/j.vesic.2025.100081","DOIUrl":"10.1016/j.vesic.2025.100081","url":null,"abstract":"<div><div>Exosomes have emerged as key mediators of inter-cellular communication, transporting a diverse array of cargos that can reflect the current biological state of the cell. Recent advancements in exosome biology have unveiled their crucial role in cell signaling and paracrine-mediated functions. In this article, we will highlight the concept of exofection. In this well-defined donor-recipient relationship, donor cells produce specific biomolecules encapsulated within exosomes, which are then delivered to recipient cells. This process is particularly crucial when recipient cells experience functional deficiencies due to physiological or pathological conditions. Upon receiving the exosomal cargo, recipient cells transiently express and exhibit the functional activity of the delivered molecules. The functional enhancement mediated by exofection is transient, gradually diminishing once the delivery from the donor cells declines, and the recipient cell no longer needs specific function. Utilizing studies from various fields, we highlight the diverse biological contexts in which exofection operates. For instance, mitochondria-containing EVs from brain endothelial cells restore mitochondrial function and tight junction integrity in ischemic brain tissues. In contrast, exosomes from TNF-α-preconditioned mesenchymal stromal cells regulate autophagy and inflammation in acute pancreatitis. Similarly, Th2 cell-derived EVs promote eosinophil survival during airway inflammation, and umbilical cord blood exosomes accelerate wound healing by enhancing angiogenesis and fibroblast function. The role of exosomes in complex pathophysiological contexts such as myocardial infarction, glioblastoma, and liver failure can be crucial. In each scenario, the donor cells' exosomal cargo modulates recipient cell functions, promoting tissue repair, immune regulation, or metastasis. This work expands the conceptual framework of exofection and emphasizes its potential impact on therapeutic development and understanding the pathophysiology of various diseases.</div></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"5 ","pages":"Article 100081"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143891490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Extracellular vesiclePub Date : 2025-06-01Epub Date: 2025-03-10DOI: 10.1016/j.vesic.2025.100068
Kaiyue Zhang, Ke Cheng
{"title":"Head-to-head comparison of extracellular vesicles from different cell sources for cardiac repair","authors":"Kaiyue Zhang, Ke Cheng","doi":"10.1016/j.vesic.2025.100068","DOIUrl":"10.1016/j.vesic.2025.100068","url":null,"abstract":"","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"5 ","pages":"Article 100068"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143578492","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}
Extracellular vesiclePub Date : 2025-06-01Epub Date: 2025-04-04DOI: 10.1016/j.vesic.2025.100077
Dongqi Li , Xiangyu Chu , Yudong Ning , Yinmo Yang , Chen Wang , Xiaodong Tian , Yanlian Yang
{"title":"The functional extracellular vesicles target tumor microenvironment for gastrointestinal malignancies therapy","authors":"Dongqi Li , Xiangyu Chu , Yudong Ning , Yinmo Yang , Chen Wang , Xiaodong Tian , Yanlian Yang","doi":"10.1016/j.vesic.2025.100077","DOIUrl":"10.1016/j.vesic.2025.100077","url":null,"abstract":"<div><div>The tumor microenvironment (TME) represents a complex, heterogeneous ecosystem that significantly influences the progression of gastrointestinal (GI) cancers, comprising diverse cellular and non-cellular components. Although chemotherapeutic agents and targeted therapies offer partial benefits for patients with GI tumors, their efficacy remains limited due to the TME's complexity. Consequently, strategies to target and modulate the TME are critical to enhancing therapeutic outcomes. Extracellular vesicles (EVs) transport a wide array of biomolecules, including proteins, lipids, and nucleic acids, playing a pivotal role in intercellular communication and TME modulation. In recent years, EVs have gained attention as potential drug delivery vehicles, owing to their nanoscale size and capacity to shuttle bioactive molecules between cells and tissues. Moreover, engineered EVs hold promise for modulating the TME to treat GI cancers by improving targeting precision and tissue penetration. This review explores the latest strategies for the production and functionalization of EVs, along with advances in utilizing EVs for targeted therapy of the TME in GI tumor treatment.</div></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"5 ","pages":"Article 100077"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143767742","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}
Extracellular vesiclePub Date : 2025-06-01Epub Date: 2025-02-24DOI: 10.1016/j.vesic.2025.100069
Yanan Sun , Junqing An , Jie Yuan , Chaoshan Han , Gangjian Qin
{"title":"A method for isolating small extracellular vesicles from parenchymal tissues","authors":"Yanan Sun , Junqing An , Jie Yuan , Chaoshan Han , Gangjian Qin","doi":"10.1016/j.vesic.2025.100069","DOIUrl":"10.1016/j.vesic.2025.100069","url":null,"abstract":"<div><div>Extracellular vesicles (EV) are released by almost all cells into the extracellular space, where they navigate through the interstitium or transfer bioactive molecules into neighboring cells, thereby regulating tissue homeostasis. Small EV (sEV) generally refer to EV with a diameter of less than 200 nm, which include exosomes formed in the endosomal system and small ectosomes assembled at and released from the plasma membrane. While techniques for isolating sEV from large body fluids auch as blood and urine are relatively well-developed, isolating sEV from solid organs remains challenging. This is because the preparations are often seen contaminated with <em>intracellular</em> vesicles due to cell breakage resulting from the treatments used to release sEV from the extracellular matrix. Here, we introduce a new gentle method that allows for the reliable isolation of sEV from heart and liver tissues with high purity and yield. The protocol involves an initial treatment of tissues with selected collagenase, followed by consecutive differential centrifugation and density-gradient ultracentrifugation to separate sEV from cells and large EV (lEV), and further density-gradient ultracentrifugation to fractionate sEV subpopulations. Characterization of the preparations reveals markedly enhanced cellular survival and reduced co-purification of extracellular non-vesicular particles as well as subcellular organelles. Moreover, we found that sEV isolated from heart, liver, and plasma are similar in morphology and size, but differ in density and protein marker distributions among sEV subpopulations. Our method may facilitate the isolation of sEV from solid tissues with better quality for further molecular characterization and functional studies.</div></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"5 ","pages":"Article 100069"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143474562","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}
Extracellular vesiclePub Date : 2025-06-01Epub Date: 2025-04-07DOI: 10.1016/j.vesic.2025.100078
Tong An , Daqin Li , Ning Wang , Feifei Ma , Tuo Li , Ningning He , Huijuan Song , Qiang Liu
{"title":"Mechanisms and potential of mesenchymal stem cell-derived exosomes for treating radiation-induced intestinal injury","authors":"Tong An , Daqin Li , Ning Wang , Feifei Ma , Tuo Li , Ningning He , Huijuan Song , Qiang Liu","doi":"10.1016/j.vesic.2025.100078","DOIUrl":"10.1016/j.vesic.2025.100078","url":null,"abstract":"<div><div>Radiation-induced intestinal injury (RIII) is a prevalent complication of radiotherapy for abdominal and pelvic tumors, characterized by acute and chronic damage to intestinal tissues. Current treatments are primarily symptomatic, lacking effective targeted therapies. Mesenchymal stem cells (MSCs), due to their immunomodulatory and regenerative properties, and their derived exosomes, have emerged as promising therapeutic options for RIII. MSC-derived exosomes exhibit anti-inflammatory, antioxidant, and tissue-repairing properties, modulating immune responses and promoting intestinal barrier restoration. Engineering of exosomes further enhances their targeting and therapeutic efficiency. This review discusses the mechanisms and therapeutic potential of MSC-derived and engineered exosomes for RIII, emphasizing their role in reducing inflammation, promoting tissue repair, and maintaining microbial balance, while addressing future challenges and prospects for clinical translation.</div></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"5 ","pages":"Article 100078"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791749","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}
Extracellular vesiclePub Date : 2025-06-01Epub Date: 2024-12-26DOI: 10.1016/j.vesic.2024.100062
Liam Hourigan , William Phillips , Amirmohammad Nasiri Kenari , Krishna Chaitanya Pavani , Chaomei Chen , An Hendrix , Lesley Cheng , Andrew F. Hill
{"title":"Mapping growth and trajectory in the field of extracellular vesicles: A scientometric analysis","authors":"Liam Hourigan , William Phillips , Amirmohammad Nasiri Kenari , Krishna Chaitanya Pavani , Chaomei Chen , An Hendrix , Lesley Cheng , Andrew F. Hill","doi":"10.1016/j.vesic.2024.100062","DOIUrl":"10.1016/j.vesic.2024.100062","url":null,"abstract":"<div><div>Extracellular vesicles (EVs) are a diverse population of membrane bound particles released by cells. They play roles in a variety of diseases and biological functions, piquing the interest of researchers and industry alike. The field is often described as undergoing ‘explosive growth’, however this growth has not been characterized in depth. Scientometrics is a quantitative approach for analyzing scientific works, allowing for a broadly focused review of the EV field. Drawing on 52210 publications from the Web of Science, this review charts the field's using the programs CiteSpace and Bibliometrix. These analyses are further enriched with data from the Dimensions database along with data from EV-TRACK, an EV-specific data source. We thoroughly describe the field's various subdomains, identifying their different lines of inquiry, their variable use of nomenclature and their progression along the translational pipeline. Cancer features prominently alongside other diseases and conditions, with the majority of research having a basic aetiological focus. These subdomains are compared against a global map of science, revealing a stable and substantial EV research community revolving around the International Society for Extracellular Vesicles ISEV and the ‘MISEV paradigm’. A shared framework of knowledge and communication, grounded in the field's history and guiding its future.</div></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"5 ","pages":"Article 100062"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143103007","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}
Extracellular vesiclePub Date : 2025-06-01Epub Date: 2025-03-22DOI: 10.1016/j.vesic.2025.100071
Yue Bi , Liang Wang , Chunyan Li , Zhiying Shan , Lanrong Bi
{"title":"Unveiling exosomal biomarkers in neurodegenerative diseases: LC-MS-based profiling","authors":"Yue Bi , Liang Wang , Chunyan Li , Zhiying Shan , Lanrong Bi","doi":"10.1016/j.vesic.2025.100071","DOIUrl":"10.1016/j.vesic.2025.100071","url":null,"abstract":"<div><div>Exosomes, small extracellular vesicles secreted by various cell types, play a critical role in intercellular communication and are increasingly recognized as key players in the progression of neurodegenerative diseases (NDs). Their ability to carry and propagate pathogenic proteins such as amyloid-beta, tau, and alpha-synuclein have established exosomal biomarkers as both key players in disease pathology and promising indicators for early diagnosis. Liquid chromatography-mass spectrometry (LC-MS) has emerged as a powerful tool for the comprehensive analysis of exosomal cargo, enabling the identification of proteins, metabolites, and other molecules associated with neurodegeneration.</div><div>This review explores the structural composition, biogenesis, and role of exosomes in the propagation of pathogenic proteins in NDs such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). It highlights the potential of exosomal biomarkers for disease diagnosis and monitoring. The foundation for LC-MS-based analyses is discussed, focusing on isolation, purification, and characterization techniques essential for reliable proteomic and metabolomic studies. The LC-MS workflow, from protein and metabolite identification to quantitative proteomics, is detailed alongside the advantages of LC-MS in uncovering exosomal biomarkers.</div><div>We delve into the application of LC-MS/MS in NDs research, showcasing its contributions to decoding disease pathology in AD, PD, and ALS by identifying specific exosomal biomarkers. Challenges such as the heterogeneity of exosome populations, variability in biofluid samples, and technical limitations in LC-MS analysis are critically examined. Finally, we discuss the future potential of LC-MS in advancing the diagnosis and treatment of NDs, emphasizing its transformative impact on biomarker discovery and personalized medicine.</div></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"5 ","pages":"Article 100071"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143684141","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}