Extracellular vesicle最新文献

{"title":"Engineering ARMMs for improved intracellular delivery of CRISPR-Cas9","authors":"Zunwei Chen,&nbsp;Qiyu Wang,&nbsp;Quan Lu","doi":"10.1016/j.vesic.2025.100082","DOIUrl":"10.1016/j.vesic.2025.100082","url":null,"abstract":"<div><div>CRISPR-Cas9-based gene editing holds enormous promise for therapeutic applications, but its effectiveness is often limited by inefficient delivery methods. This study explores the potential of arrestin domain-containing protein 1 (ARRDC1)-mediated microvesicles (ARMMs)—a type of extracellular vesicles formed at the plasma membrane—as a novel platform for packaging and delivering CRISPR-Cas9 complexes. We achieved efficient Cas9 packaging into ARMMs by directly fusing Cas9 with ARRDC1. Two different ARRDC1-Cas9 fusion constructs were designed, and both demonstrated gene-editing efficiency comparable to unmodified Cas9. The fusion with a shorter version of ARRDC1 (sARRDC1), which includes only the minimal motifs required for vesicle budding, proved particularly effective in enhancing Cas9 packaging. Additionally, the incorporation of vesicular stomatitis virus glycoprotein (VSV-G) further improved ARMMs budding and Cas9 encapsulation. We tested gene editing in U2OS cells with an exogenous GFP gene and in human neuronal cells targeting the endogenous amyloid precursor protein (APP) gene, which is associated with the Alzheimer's disease. The combination of ARMMs and VSV-G resulted in high editing efficiency, with ARMMs targeting the APP gene in neuronal cells significantly reducing pathogenic amyloid peptides. These results highlight ARMMs as a versatile and effective platform for CRISPR-Cas9 delivery, with strong potential for therapeutic applications in neurodegenerative and other genetic diseases.</div></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"5 ","pages":"Article 100082"},"PeriodicalIF":0.0,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143927767","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":"Exofection by exosomes: A transient functional cargo transfer","authors":"Ramkumar Menon,&nbsp;Madhuri Tatiparthy,&nbsp;Jessica Selim,&nbsp;Isidore Mushimiyimana,&nbsp;Brinley Harrington,&nbsp;Awanit Kumar,&nbsp;Lauren Richardson,&nbsp;Emmanuel Amabebe,&nbsp;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":"2025-05-01","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}

{"title":"MicroRNAs won the Nobel Prize. Now, can extracellular vesicles help them become drugs?","authors":"Vanessa YiRan Li ,&nbsp;Nicole Rosas ,&nbsp;Sharon Fleischer ,&nbsp;Gordana Vunjak-Novakovic ,&nbsp;Ke Cheng","doi":"10.1016/j.vesic.2025.100080","DOIUrl":"10.1016/j.vesic.2025.100080","url":null,"abstract":"<div><div>The 2024 Nobel Prize recognized microRNAs (miRNAs) as transformative regulators of gene expression. However, their clinical potential has been constrained by instability and delivery challenges. Extracellular vesicles (EVs), as natural carriers of miRNAs, address these limitations by protecting miRNAs from degradation and enabling their precise targeting. As such, harnessing EVs for miRNA delivery has the potential to redefine therapeutic approaches and offer innovative strategies to tackle the most challenging diseases of the 21st century. In this perspective, we examine the advantages and hurdles of EV-mediated miRNA delivery, from state-of-the-art research to its path toward commercialization. This article aims to inspire readers with the promise of EVs and miRNAs as revolutionary tools for future medicine.</div></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"5 ","pages":"Article 100080"},"PeriodicalIF":0.0,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143854484","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":"Beyond conventional biomarkers: Emerging importance of extracellular vesicles in osteoarthritis, metabolic disorders and cardiovascular disease","authors":"Madison Coward-Smith ,&nbsp;Ye Zhang ,&nbsp;Chantal Donovan ,&nbsp;Richard Y. Kim ,&nbsp;Baoming Wang ,&nbsp;Razia Zakarya ,&nbsp;Hui Chen ,&nbsp;Jiao Jiao Li ,&nbsp;Brian G. Oliver","doi":"10.1016/j.vesic.2025.100079","DOIUrl":"10.1016/j.vesic.2025.100079","url":null,"abstract":"<div><div>Extracellular vesicles (EVs), initially recognized for their roles in intercellular communication, are being increasingly explored for applications in the diagnosis and therapy of various diseases, particularly those driven by chronic inflammation. This review provides insight into the defining characteristics and functions of EVs, focusing on their role in contributing to and acting as potential therapeutics for chronic inflammatory diseases, including osteoarthritis, metabolic disorders such as obesity and metabolic dysfunction associated fatty liver disease, and cardiovascular diseases such as atherosclerosis and ischaemic stroke. Finally, the issues limiting EV translation from bench to bedside, and the outlook of EV research are discussed.</div></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"5 ","pages":"Article 100079"},"PeriodicalIF":0.0,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143843743","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":"Optimization and assessment of an integrated workflow for the isolation and proteomic analysis of small urinary extracellular vesicles (suEVs)","authors":"Yilan Hu ,&nbsp;Jifeng Wang ,&nbsp;Xiaoqing Qing ,&nbsp;Tanxi Cai ,&nbsp;Lili Niu ,&nbsp;Xiang Ding ,&nbsp;Zhensheng Xie ,&nbsp;Mengmeng Zhang ,&nbsp;Xiaojing Guo ,&nbsp;Xiulan Chen ,&nbsp;Fuquan Yang","doi":"10.1016/j.vesic.2025.100076","DOIUrl":"10.1016/j.vesic.2025.100076","url":null,"abstract":"<div><div>Small urinary extracellular vesicles (suEVs) are 50–200 nm membrane-delimited vesicles secreted mainly by urothelial cells. suEVs have become a promising non-invasive source of biomarkers for urinary diseases. However, suEV proteomic studies are limited due to the low concentration of EVs in urine samples and poor proteomic coverage caused by high abundant uromodulin. In this study, we compared four methods for suEV isolation, including ultracentrifugation (UC), ultracentrifugation with DTT treatment (DTT + UC), filtration and ultracentrifugation (F + UC), and filtration and ultrafiltration (F + UF). We evaluated their recovery, EV purity, and proteomic coverage using multiple techniques. The combination of filtration and ultracentrifugation (F + UC) showed the best performance with efficient removal of uromodulin fibers and successful in-depth proteome identification. Furthermore, we performed a deep-going proteomic analysis and characterized suEV subsets purified by the four methods. Lastly, we developed a statistical approach to evaluate universal suEV proteins, independent of the isolation techniques used, by calculating the correlation between protein abundance and sample purity. This study provided an integrated workflow for the isolation and proteomic analysis of suEVs, which could facilitate clinical biomarker discovery and diagnosis in urology disease.</div></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"5 ","pages":"Article 100076"},"PeriodicalIF":0.0,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143829059","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":"Mechanisms and potential of mesenchymal stem cell-derived exosomes for treating radiation-induced intestinal injury","authors":"Tong An ,&nbsp;Daqin Li ,&nbsp;Ning Wang ,&nbsp;Feifei Ma ,&nbsp;Tuo Li ,&nbsp;Ningning He ,&nbsp;Huijuan Song ,&nbsp;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":"2025-04-07","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}

{"title":"The mechanisms and application prospects of exosomes in acute myocardial infarction","authors":"Peng Zhou ,&nbsp;Jia Zhang ,&nbsp;Leilei Zhang ,&nbsp;Jiangwei Yan ,&nbsp;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":"2025-04-05","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":"The functional extracellular vesicles target tumor microenvironment for gastrointestinal malignancies therapy","authors":"Dongqi Li ,&nbsp;Xiangyu Chu ,&nbsp;Yudong Ning ,&nbsp;Yinmo Yang ,&nbsp;Chen Wang ,&nbsp;Xiaodong Tian ,&nbsp;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":"2025-04-04","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}

{"title":"Role of extracellular vesicles in immune modulation, angiogenesis, progression and therapeutic resistance of glioblastoma","authors":"Muhammad Izhar,&nbsp;Ahed H. Kattaa,&nbsp;Amirhossein Akhavan-Sigari,&nbsp;Elaheh Shaghaghian,&nbsp;Yusuke S. Hori,&nbsp;Fred C. Lam,&nbsp;Deyaaldeen AbuReesh,&nbsp;Sara C. Emrich,&nbsp;Louisa Ustrzynski,&nbsp;Armine Tayag,&nbsp;Steven D. Chang,&nbsp;David J. Park","doi":"10.1016/j.vesic.2025.100075","DOIUrl":"10.1016/j.vesic.2025.100075","url":null,"abstract":"<div><div>Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor in adults, with a poor prognosis and high recurrence rates despite advancements in treatment. The tumor microenvironment (TME) of GBM is very complex and includes various cell types, such as immune cells, endothelial cells, astrocytes, and microglia. The TME plays a crucial role in the development of GBM and its resistance to therapy. One important part of the TME is extracellular vesicles (EVs), which help cells communicate and contribute to different aspects of GBM progression. They help the tumor grow and spread by increasing cellular proliferation, invasion, and survival. They also play a key role in angiogenesis by transferring pro-angiogenic factors to endothelial cells, which help form new blood vessels that provide the tumor with essential nutrients and oxygen. Within the context of immune modulation, EVs derived from GBM cells contain immunosuppressive molecules that alter the function of immune cells in the TME, enabling the tumor to escape immune surveillance. This immunosuppressive environment is marked by elevated levels of regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), and tumor-associated macrophages (TAMs). Furthermore, EVs contribute to therapeutic resistance by transferring drug-resistance factors from resistant to sensitive tumor cells, enhancing their capacity to withstand chemotherapy and radiotherapy. The RNA cargo of EVs, which includes microRNAs and long non-coding RNAs, plays a crucial role in modulating gene expression and cellular responses to treatment. In conclusion, EVs are vital in the development and progression of GBM by influencing angiogenesis, immune modulation, and therapeutic resistance. Targeting EV-mediated communication presents a promising therapeutic strategy for addressing the challenges posed by this deadly brain tumor.</div></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"5 ","pages":"Article 100075"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143738368","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":"Unveiling exosomal biomarkers in neurodegenerative diseases: LC-MS-based profiling","authors":"Yue Bi ,&nbsp;Liang Wang ,&nbsp;Chunyan Li ,&nbsp;Zhiying Shan ,&nbsp;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":"2025-03-22","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}