Extracellular vesicles and circulating nucleic acids最新文献

{"title":"Therapeutic extracellular vesicles isolated from mesenchymal stem cells: properties, isolation, characterization, and applications in optic neuropathies.","authors":"Jing Zhou, Xi Lin, Lijuan Yan, Zhe Cha, Jiarui Li, Haiwei Xu","doi":"10.20517/evcna.2026.06","DOIUrl":"10.20517/evcna.2026.06","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) are promising cell-free therapeutic agents because of their low immunogenicity, excellent biocompatibility, and intrinsic capacity for intercellular communication. Of these, mesenchymal stem cell-derived EVs (MSC-EVs) have attracted considerable interest for their potential in treating optic neuropathies; however, their clinical translation remains limited by standardized manufacturing, quality evaluation, and mechanistic understanding. This review summarizes key advances in therapeutic EV development, including MSC culture, EV production, isolation, and characterization, with a focus on the current strategies and limitations of EV quality assessment. In addition, we propose a pathological-node-based framework to integrate the current evidence for EV therapies with optic neuropathies. Despite differences in EV sources, molecular composition, and proposed mechanisms, the therapeutic effects of diverse EV preparations converge on three shared pathological processes: retinal ganglion cell (RGC) preservation, neuroinflammatory regulation, and metabolic homeostasis maintenance. Finally, we discuss major challenges for clinical translation, including EV heterogeneity, functional EV subpopulations, targeted delivery, engineering strategies, and the establishment of biologically relevant potency assays. This review highlights the need to shift EV studies from empirical preparation toward mechanism-driven design and functional evaluation, thereby facilitating the development of clinically translatable EV-based therapies.</p>","PeriodicalId":520322,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"7 3","pages":"1249-1275"},"PeriodicalIF":8.5,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673256/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149218011","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-delivered siRNA targeting RCN1 suppresses acute myeloid leukemia through TFAM-dependent mtDNA-cGAS-STING signaling.","authors":"Huan Chen, Na An, Linlin Yang, Jin Lou, Yuming Pan, Minh T N Le, Xin Du, Qiaoxia Zhang","doi":"10.20517/evcna.2026.36","DOIUrl":"10.20517/evcna.2026.36","url":null,"abstract":"<p><p><b>Aim:</b> Acute myeloid leukemia (AML) remains a highly aggressive hematologic malignancy with limited therapeutic options. This study aimed to elucidate how reticulocalbin-1 (RCN1) regulates mitochondrial DNA (mtDNA)-mediated innate immune signaling in AML and to evaluate the therapeutic potential of extracellular vesicle (EV)-mediated small interfering RNA (siRNA) delivery targeting RCN1. <b>Methods:</b> Stable RCN1 knockdown was achieved in AML cells using lentiviral delivery of short hairpin RNA. Mitochondrial transcription factor A (TFAM) expression, mtDNA leakage, and activation of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING)-type I interferon pathway were analyzed by immunoblotting and quantitative polymerase chain reaction. Protein interactions were assessed by co-immunoprecipitation, proximity ligation assay, and immunofluorescence. TFAM rescue experiments were performed to evaluate its contribution to the downstream effects of RCN1 knockdown. For translational evaluation, EVs were isolated and characterized by transmission electron microscopy, nanoparticle tracking analysis, and marker protein detection, followed by loading with siRNA targeting RCN1. Therapeutic efficacy and safety were assessed in an AML xenograft mouse model. <b>Results:</b> RCN1 knockdown reduced TFAM expression, leading to cytoplasmic mtDNA accumulation and activation of the cGAS-STING-type I interferon signaling pathway. Restoration of TFAM expression attenuated mtDNA leakage and downstream signaling. EV-delivered siRCN1 effectively suppressed tumor growth <i>in vivo</i> without detectable toxicity. <b>Conclusion:</b> RCN1 silencing destabilizes mtDNA integrity and activates innate immune signaling in AML. EV-based delivery of siRCN1 may represent a promising and potentially safe therapeutic strategy for AML.</p>","PeriodicalId":520322,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"7 3","pages":"1228-1248"},"PeriodicalIF":8.5,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673257/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149217924","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":"From bug to bubble: the rising prominence of <i>Lactobacillus</i>-derived extracellular vesicles as postbiotic wound healers.","authors":"Yuting Li, Min Zhang, Yirong Wang, Xiangyu Sang, Wenchen Cai, Yejiao Shi, Honggang Hu","doi":"10.20517/evcna.2026.59","DOIUrl":"10.20517/evcna.2026.59","url":null,"abstract":"<p><p>The therapeutic landscape of probiotics is undergoing a paradigm shift from the live bacteria \"bug\" to the bioactive extracellular vesicles (EVs) \"bubble\" they secrete. Owing to their essential defense and metabolic functions, EVs derived from <i>Lactobacillus</i>, a genus of anaerobic or microaerophilic probiotics well known for their ability to ferment carbohydrates into lactic acid, have garnered particular interest for wound healing. As such, the presented mini-review began by elucidating why these <i>Lactobacillus-</i>derived EVs (L-EVs) attract upward attention by highlighting their superior safety, stability, multifunctionality, customizability, and scalability. This was followed by elaborating how these L-EVs accelerate wound healing by detailing their multifaceted mechanisms, including removing bacteria, reprogramming the microenvironment, repairing tissue, and remodeling the matrix during the wound-healing process. Lastly, it ended by envisioning where these L-EVs head for future therapy by addressing the translational hurdles, such as the lack of isolation and purification standardizations, the existing cargo and batch variabilities, as well as the ambiguous classification and regulation of L-EVs, which must be overcome to push them from bench to bedside. Moreover, it further proposed a specialized database based on artificial intelligence and multi-omics, the combined modification based on diverse engineering approaches, as well as the advanced formulation based on the material engineering strategies of L-EVs in the future to integrate the next generation of wound management modalities with optimal treatment efficacy.</p>","PeriodicalId":520322,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"7 3","pages":"1217-1227"},"PeriodicalIF":8.5,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149218036","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":"Olfactory ensheathing cell-derived extracellular vesicles protect the degenerated retinal pigment epithelium by delivering phagocytosis-related proteins.","authors":"Siyu Chen, Xi Lin, Zhe Cha, Hui Gao, Jing Zhou, Shujia Huo, Cao Yang, Jiahui Kang, Lingyue Mo, Lijuan Yan, Yijian Li, Xinying Hu, Luodan A, Xiaotang Fan, Jing Xie, Haiwei Xu","doi":"10.20517/evcna.2026.50","DOIUrl":"10.20517/evcna.2026.50","url":null,"abstract":"<p><p><b>Aim:</b> Olfactory ensheathing cells (OECs) are commonly utilized in cell-based therapies for neurodegenerative diseases and central nervous system injuries, due to their unique properties of suppressing gliosis and providing neuroprotection. Small extracellular vesicles (sEVs) have emerged as promising therapeutic agents. This study aimed to investigate OEC-sEVs' effect on retinal degeneration. <b>Methods:</b> Proteomics analysis identified differentially expressed proteins between OEC-sEVs and OECs. We conducted subretinal injection of OEC-sEVs and assessed their protective mechanisms in degenerative retina. Real-time quantitative PCR and Western blot were used to detect the expression of phagocytosis-related molecules in retinal pigment epithelium (RPE) cells. <b>Results:</b> Proteomics analysis revealed that proteins enriched in OEC-sEVs were associated with phagocytosis. Following injection into the subretinal spaces of Royal College of Surgeons (RCS) rats, OEC-sEVs were internalized by RPE cells, leading to the transient upregulation of tyrosine-protein kinase Mer (MerTK), activation of the downstream phosphoinositide 3-kinase/Akt signaling pathway, and restoration of the phagocytic activity of RPE cells towards the photoreceptor outer segments. This delayed photoreceptor degeneration, thereby improving retinal function in RCS rats. In the ARPE-19 cell line treated with the specific MerTK inhibitor UNC2881, enhanced phagocytosis of fluorescent particles and porcine photoreceptor outer segments was observed following OEC-sEV internalization. <b>Conclusion:</b> OEC-sEVs were abundant in proteins associated with phagocytosis, which may partially compensate for the phagocytic deficit of the RPE cells observed in a retinitis pigmentosa rat model via the MerTK-related signaling pathway.</p>","PeriodicalId":520322,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"7 3","pages":"1189-1216"},"PeriodicalIF":8.5,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673258/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149218052","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 for Alzheimer's disease therapy: mechanisms, engineering strategies, and clinical translation.","authors":"Ailin Wu, Yan Zeng, Yilin Huang, Legao Chen, Shunyuan Guo, Jianwei Wang, Xiaozhou Mou, Xiaoru Chang","doi":"10.20517/evcna.2026.43","DOIUrl":"10.20517/evcna.2026.43","url":null,"abstract":"<p><p>Alzheimer's disease (AD), a progressive neurodegenerative disorder, remains a major global health challenge owing to its complex pathogenesis and the presence of the blood-brain barrier (BBB), which substantially limits the delivery of effective therapeutics to the brain. Extracellular vesicles (EVs), which exhibit favorable biocompatibility, low immunogenicity, and the potential to cross or bypass the BBB under specific conditions, have emerged as promising therapeutic agents and delivery platforms for AD. This review focuses on the therapeutic potential of EV-based interventions in AD and summarizes recent advances in EV-mediated modulation of AD-related pathological processes, including amyloid-β (Aβ) clearance, tau protein regulation, neuroinflammation suppression, oxidative stress attenuation, and synaptic repair. Although EV-based therapies offer notable advantages, such as targeted BBB penetration and reduced immunogenic responses, their clinical translation remains constrained by safety concerns, including off-target effects, dose-dependent toxicity, and potential disturbances in neuroplasticity. In addition, this review discusses EV engineering strategies aimed at regulating the gut-brain axis (GBA), enhancing brain targeting, and advancing clinical translation. EV-based therapeutic interventions should therefore be developed within a safety-oriented framework supported by rigorous short- and long-term toxicological evaluation. Overall, this review highlights the therapeutic promise of EVs for AD while underscoring the need for rational engineering, standardized characterization, and safety-centered translational strategies to ensure clinical feasibility.</p>","PeriodicalId":520322,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"7 3","pages":"1158-1188"},"PeriodicalIF":8.5,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673255/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149218019","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":"Comparative analysis of small extracellular vesicles in peritoneal fluid from endometriosis and non-endometriosis patients: a pilot case-control study.","authors":"Barbara Bortot, Alice Gualerzi, Roberta Di Florio, Silvia Picciolini, Aurora Mangolini, Francesco Valle, Marco Brucale, Federico Romano, Giuseppe Ricci, Stefania Biffi","doi":"10.20517/evcna.2026.23","DOIUrl":"10.20517/evcna.2026.23","url":null,"abstract":"<p><p><b>Aim:</b> Endometriosis is a chronic inflammatory disorder requiring clinical examination, imaging, and surgical intervention for accurate assessment. The aim of the present study was to provide a detailed biophysical and biochemical characterization of small extracellular vesicles (sEVs) derived from peritoneal fluid, and to explore disease-associated molecular differences that may inform future investigations. <b>Methods:</b> sEVs were isolated from the peritoneal fluid of women with endometriosis (<i>n</i> = 7), women without endometriosis who underwent surgery for benign, noninflammatory conditions (<i>n</i> = 7), and follicular fluid samples (<i>n</i> = 3). The tetraspanin profile of the samples was determined using single-particle interferometric reflectance imaging sensing. After size exclusion chromatography and ultracentrifugation, atomic force microscopy (AFM) and Raman spectroscopy were employed to characterize the sEVs. <b>Results:</b> Prominent Raman spectral variations in peritoneal sEVs between control women and those with endometriosis were observed at 891 cm^-1 (proteins) and 968 cm^-1 (lipids, CH wagging). Statistical analysis of molecular components influencing the Raman signature of sEVs suggest that their lipid composition appears to be influenced by the pathophysiology of endometriosis, reflecting changes similar to those observed in the eutopic endometrium in previous studies. sEVs isolated from peritoneal fluid and follicular fluid have markedly distinct biochemical compositions and morphometric properties. sEVs from follicular fluid were significantly smaller in size and exhibited a higher rigidity in this pilot cohort. <b>Conclusion:</b> Distinct biophysical and biochemical differences in sEVs from endometriosis patients are documented in this pilot study, contributing to a deeper characterization of disease-associated extracellular vesicle (EV) alterations. Variations between follicular and peritoneal fluid sEVs suggest unique functional roles in reproductive health. These findings are hypothesis-generating and warrant validation in larger, well-controlled cohorts before any diagnostic application can be claimed.</p>","PeriodicalId":520322,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"7 3","pages":"1143-1157"},"PeriodicalIF":8.5,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149217927","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":"Glucosylceramides trigger the shedding of alpha-synuclein laden ectosomes.","authors":"Irmgard Tegeder","doi":"10.20517/evcna.2026.51","DOIUrl":"10.20517/evcna.2026.51","url":null,"abstract":"","PeriodicalId":520322,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"7 3","pages":"1136-1142"},"PeriodicalIF":8.5,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673449/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149218041","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 report on the 2025 global conference on research and application of Chinese herbal medicine-derived extracellular vesicles.","authors":"Zesheng Lu, Yingqi Cao, Wencong Shen, Zhengting Wu, Huijing Li, Dongxiao Li, Zimei Chen, Qing Zhao, Kewei Zhao","doi":"10.20517/evcna.2025.157","DOIUrl":"https://doi.org/10.20517/evcna.2025.157","url":null,"abstract":"<p><p>This conference report summarizes the Global Conference on Research and Application of Chinese herbal Medicine Derived Extracellular Vesicles-like Particles (CHM-EVLPs) held in Guangzhou. The conference gathered worldwide scholars to exchange cutting-edge advances in extracellular vesicle (EV) extraction, functional modification, disease treatment, and industrial transformation via six themed forums covering basic research, fruit EVLPs, laboratory testing, HIV intervention, and youth innovation. Experts shared standardized separation technologies, engineered modification strategies and multi-target therapeutic potentials of plant-derived extracellular vesicles (PDVs) against tumors, intestinal disorders, metabolic diseases and neurodegenerative injuries, while discussing key bottlenecks including large-scale production, quality control and regulatory guidelines. Cross-kingdom molecular communication, oral nano-delivery systems and interdisciplinary combinations with microneedles and artificial intelligence were highlighted as promising research directions. The event promoted international academic cooperation, clarified translational challenges of CHM-EVLPs products, and laid a foundation for advancing standardized, industrialized and globalized development of PDVs to facilitate worldwide medical care improvement.</p>","PeriodicalId":520322,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"7 3","pages":"1116-1135"},"PeriodicalIF":8.5,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149217938","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":"Exercise-induced muscle extracellular vesicles reprogram brain microglia to enhance amyloid clearance in Alzheimer's disease.","authors":"Toshihide Takeuchi, Yoshitaka Nagai","doi":"10.20517/evcna.2026.73","DOIUrl":"10.20517/evcna.2026.73","url":null,"abstract":"","PeriodicalId":520322,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"7 3","pages":"1112-1115"},"PeriodicalIF":8.5,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149217981","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":"Isolation-free detection of extracellular vesicles using Janus particles.","authors":"Rienk Nieuwland, Edwin van der Pol, Agustin Enciso-Martinez","doi":"10.20517/evcna.2026.71","DOIUrl":"10.20517/evcna.2026.71","url":null,"abstract":"","PeriodicalId":520322,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"7 3","pages":"1108-1111"},"PeriodicalIF":8.5,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673459/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149218009","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}