Extracellular vesicles and circulating nucleic acids最新文献

Flow cytometry for extracellular vesicle characterization in COVID-19 and post-acute sequelae of SARS-CoV-2 infection 用流式细胞术鉴定 COVID-19 和 SARS-CoV-2 感染急性后遗症中细胞外囊泡的特征

Extracellular vesicles and circulating nucleic acids Pub Date : 2024-08-09 DOI: 10.20517/evcna.2024.20

Marialaura Fanelli, Vita Petrone, Rossella Chirico, Claudia Maria Radu, A. Minutolo, Claudia Matteucci

{"title":"Flow cytometry for extracellular vesicle characterization in COVID-19 and post-acute sequelae of SARS-CoV-2 infection","authors":"Marialaura Fanelli, Vita Petrone, Rossella Chirico, Claudia Maria Radu, A. Minutolo, Claudia Matteucci","doi":"10.20517/evcna.2024.20","DOIUrl":"https://doi.org/10.20517/evcna.2024.20","url":null,"abstract":"Infection with SARS-CoV-2, the virus responsible for COVID-19 diseases, can impact different tissues and induce significant cellular alterations. The production of extracellular vesicles (EVs), which are physiologically involved in cell communication, is also altered during COVID-19, along with the dysfunction of cytoplasmic organelles. Since circulating EVs reflect the state of their cells of origin, they represent valuable tools for monitoring pathological conditions. Despite challenges in detecting EVs due to their size and specific cellular compartment origin using different methodologies, flow cytometry has proven to be an effective method for assessing the role of EVs in COVID-19. This review summarizes the involvement of plasmatic EVs in COVID-19 patients and individuals with Long COVID (LC) affected by post-acute sequelae of SARS-CoV-2 infection (PASC), highlighting their dual role in exerting both pro- and antiviral effects. We also emphasize how flow cytometry, with its multiparametric approach, can be employed to characterize circulating EVs, particularly in infectious diseases such as COVID-19, and suggest their potential role in chronic impairments during post-infection.","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"71 14","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141922498","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}

引用次数: 0

Extracellular vesicles in tumor-adipose tissue crosstalk: key drivers and therapeutic targets in cancer cachexia 肿瘤-脂肪组织串联过程中的细胞外囊泡：癌症恶病质的关键驱动因素和治疗靶点

Extracellular vesicles and circulating nucleic acids Pub Date : 2024-07-23 DOI: 10.20517/evcna.2024.36

Cátia C Ramos, José Pires, Esperanza González, C. Garcia-Vallicrosa, Celso A. Reis, J. Falcón-Perez, D. Freitas

{"title":"Extracellular vesicles in tumor-adipose tissue crosstalk: key drivers and therapeutic targets in cancer cachexia","authors":"Cátia C Ramos, José Pires, Esperanza González, C. Garcia-Vallicrosa, Celso A. Reis, J. Falcón-Perez, D. Freitas","doi":"10.20517/evcna.2024.36","DOIUrl":"https://doi.org/10.20517/evcna.2024.36","url":null,"abstract":"Cancer cachexia is a complex metabolic syndrome characterized by unintentional loss of skeletal muscle and body fat. This syndrome is frequently associated with different types of cancer and negatively affects the prognosis and outcome of these patients. It involves a dynamic interplay between tumor cells and adipose tissue, where tumor-derived extracellular vesicles (EVs) play a crucial role in mediating intercellular communication. Tumor cells release EVs containing bioactive molecules such as hormones (adrenomedullin, PTHrP), pro-inflammatory cytokines (IL-6), and miRNAs (miR-1304-3p, miR-204-5p, miR-155, miR-425-3p, miR-146b-5p, miR-92a-3p), which can trigger lipolysis and induce the browning of white adipocytes contributing to a cancer cachexia phenotype. On the other hand, adipocyte-derived EVs can reprogram the metabolism of tumor cells by transporting fatty acids and enzymes involved in fatty acid oxidation, resulting in tumor growth and progression. These vesicles also carry leptin and key miRNAs (miR-155-5p, miR-10a-3p, miR-30a-3p, miR-32a/b, miR-21), thereby supporting tumor cell proliferation, metastasis formation, and therapy resistance. Understanding the intricate network underlying EV-mediated communication between tumor cells and adipocytes can provide critical insights into the mechanisms driving cancer cachexia. This review consolidates current knowledge on the crosstalk between tumor cells and adipose tissue mediated by EVs and offers valuable insights for future research. It also addresses controversial topics in the field and possible therapeutic approaches to manage cancer cachexia and ultimately improve patient outcomes and quality of life.","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"143 16","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141810833","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}

引用次数: 0

Harnessing crosstalk between extracellular vesicles and viruses for disease diagnostics and therapeutics 利用细胞外囊泡和病毒之间的串扰进行疾病诊断和治疗

Extracellular vesicles and circulating nucleic acids Pub Date : 2024-07-07 DOI: 10.20517/evcna.2024.30

Xinxi Zhu, Xiuhui Lin, Liang Hu, Liangxing Wang, Qingfu Zhu

{"title":"Harnessing crosstalk between extracellular vesicles and viruses for disease diagnostics and therapeutics","authors":"Xinxi Zhu, Xiuhui Lin, Liang Hu, Liangxing Wang, Qingfu Zhu","doi":"10.20517/evcna.2024.30","DOIUrl":"https://doi.org/10.20517/evcna.2024.30","url":null,"abstract":"Extracellular vesicles (EVs) are increasingly acknowledged as important mediators of intercellular communication, closely related to the occurrence and development of a variety of diseases. Numerous studies have demonstrated that EVs play a multifaceted role in the infection process of viral diseases, elucidating their ability to both facilitate viral spread and inhibit infection progression. These versatile entities not only enhance infection rates and widen the scope of viral infection through the transmission of entire viruses or viral genomes, but also trigger antiviral responses and prompt cytokine secretion near the infection site, thereby fortifying the host's defense mechanisms and safeguarding neighboring cells against infection. This complicated crosstalk between EVs and viral infections prompts a deeper exploration into their roles in potential clinical applications. In this review, we aim to encapsulate the recent advances in understanding the intricate interplay between viruses and EVs, shedding light on the mechanisms underlying this vesicle-to-virion crosstalk. Furthermore, we underscore the significance of harnessing this knowledge for diagnostic and therapeutic functions in combating viral diseases.","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":" 17","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141670138","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}

引用次数: 0

Endosomal escape mechanisms of extracellular vesicle-based drug carriers: lessons for lipid nanoparticle design 基于细胞外囊泡的药物载体的内泌体逃逸机制：脂质纳米粒子设计的启示

Extracellular vesicles and circulating nucleic acids Pub Date : 2024-07-05 DOI: 10.20517/evcna.2024.19

Lasse Hagedorn, David C. Jürgens, Olivia M. Merkel, Benjamin Winkeljann

引用次数: 0

Synovial fluid extracellular vesicles as arthritis biomarkers: the added value of lipid-profiling and integrated omics 作为关节炎生物标记物的滑膜液细胞外囊泡：脂质分析和综合全息技术的附加值

Extracellular vesicles and circulating nucleic acids Pub Date : 2024-06-13 DOI: 10.20517/evcna.2024.14

L. Varela, Chris H.A. van de Lest, P. V. van Weeren, M. Wauben

{"title":"Synovial fluid extracellular vesicles as arthritis biomarkers: the added value of lipid-profiling and integrated omics","authors":"L. Varela, Chris H.A. van de Lest, P. V. van Weeren, M. Wauben","doi":"10.20517/evcna.2024.14","DOIUrl":"https://doi.org/10.20517/evcna.2024.14","url":null,"abstract":"Arthritis, a diverse group of inflammatory joint disorders, poses great challenges in early diagnosis and targeted treatment. Timely intervention is imperative, yet conventional diagnostic methods are not able to detect subtle early symptoms. Hence, there is an urgent need for specific biomarkers that discriminate between different arthritis forms and for early diagnosis. The pursuit of such precise diagnostic tools has prompted a growing interest in extracellular vesicles (EVs). EVs, released by cells in a regulated fashion, are detectable in body fluids, including synovial fluid (SF), which fills the joint space. They provide insights into the intricate molecular landscapes of arthritis, and this has stimulated the search for minimally invasive EV-based diagnostics. As such, the analysis of EVs in SF has become a focus for identifying EV-based biomarkers for joint disease endotyping, prognosis, and progression. EVs are composed of a lipid bilayer and a wide variety of different cargo types, of which proteins and RNAs are widely investigated. In contrast, membrane lipids of EVs, especially the abundance, presence, or absence of specific lipids and their contribution to the biological activity of EVs, are largely overlooked in EV research. Furthermore, the identification of specific combinations of different EV components acting in concert in EVs can fuel the definition of composite biomarkers. We here provide a state-of-the-art overview of the knowledge on SF-derived EVs with emphasis on lipid analysis and we give an example of the added value of integrated proteomics and lipidomics analysis in the search for composite EV-associated biomarkers.","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"51 30","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141345016","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}

引用次数: 0

Mitochondria-derived vesicles: potential nano-batteries to recharge the cellular powerhouse. 线粒体衍生囊泡：为细胞动力室充电的潜在纳米电池。

Extracellular vesicles and circulating nucleic acids Pub Date : 2024-06-01 Epub Date: 2024-06-10 DOI: 10.20517/evcna.2023.71

Shalini Mishra, Gagan Deep

{"title":"Mitochondria-derived vesicles: potential nano-batteries to recharge the cellular powerhouse.","authors":"Shalini Mishra, Gagan Deep","doi":"10.20517/evcna.2023.71","DOIUrl":"10.20517/evcna.2023.71","url":null,"abstract":"Mitochondria dysfunction is increasingly recognized as a critical factor in various pathogenic processes. The mechanism governing mitochondrial quality control serves as an adaptive response, ensuring the preservation of mitochondrial morphology, quantity, and overall function, crucial for cell survival. The generation of mitochondria-derived vesicles (MDVs) is one of the processes of mitochondrial quality control. Recent literature has suggested MDV heterogeneity; however, the detailed characteristics of various MDV subtypes still need to be studied better. Recent studies have shown that MDVs also play a role in inter-organelle communication for mitochondria besides quality control. For instance, Hazan et al. demonstrated that functional mitochondria from Saccharomyces cerevisiae release vesicles independent of the fission machinery. These vesicles, falling within the typical size range of MDVs, were selectively loaded with mitochondrial proteins, especially with functional ATP synthase subunits. Intriguingly, these MDVs maintained membrane potential and could generate ATP. Moreover, MDVs could fuse with naïve mitochondria, transferring their ATP generation machinery. Lastly, this study revealed a potential delivery mechanism of ATP-producing vesicles, presenting a promising avenue to rejuvenate ATP-deficient mitochondria. Overall, this study unveils a novel mechanism for inter-organelle communication by vesicles, which is crucial for maintaining cellular homeostasis and could also be important in pathological conditions.","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"5 2","pages":"271-275"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11293460/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141876876","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}

引用次数: 0

Delivery of miR-214 via extracellular vesicles downregulates Xbp1 expression and pro-inflammatory cytokine genes in macrophages. 通过细胞外囊泡输送 miR-214 可下调巨噬细胞中 Xbp1 的表达和促炎细胞因子基因。

Extracellular vesicles and circulating nucleic acids Pub Date : 2024-06-01 Epub Date: 2024-05-28 DOI: 10.20517/evcna.2023.64

Gonzalo Almanza, Stephen Searles, Maurizio Zanetti

{"title":"Delivery of miR-214 via extracellular vesicles downregulates Xbp1 expression and pro-inflammatory cytokine genes in macrophages.","authors":"Gonzalo Almanza, Stephen Searles, Maurizio Zanetti","doi":"10.20517/evcna.2023.64","DOIUrl":"10.20517/evcna.2023.64","url":null,"abstract":"Aim: Tumor-infiltrating macrophages are tumor-promoting and show activation of the unfolded protein response (UPR). The transcription factor X-box binding protein 1 (XBP1) is a conserved element of the UPR. Upon activation, the UPR mediates the transcriptional activation of pro-inflammatory cytokines and immune suppressive factors, hence contributing to immune dysregulation in the tumor microenvironment (TME). miR-214 is a short non-coding miRNA that targets the 3'-UTR of the Xbp1 transcript. Here, we tested a new method to efficiently deliver miR-214 to macrophages as a potential new therapeutic approach.Methods: We generated miR-214-laden extracellular vesicles (iEV-214) in a murine B cell and demonstrated that iEV-214 were enriched in miR-214 between 1,500 - 2,000 fold relative to control iEVs.Results: Bone marrow-derived macrophages (BMDM) treated with iEV-214 for 24 h underwent a specific enrichment in miR-214, suggesting transfer of the miR-214 payload from the iEVs to macrophages. iEV-214 treatment of BMDM markedly reduced (> 50%) Xbp1 transcription under endoplasmic reticulum stress conditions compared to controls. Immune-related genes downstream of XBP1s (Il-6, Il-23p19, and Arg1) were also reduced by 69%, 51%, and 34%, respectively.Conclusions: Together, these data permit to conclude that iEV-214 are an efficient strategy to downregulate the expression of Xbp1 mRNA and downstream genes in macrophages. We propose miRNA-laden iEVs are a new approach to target macrophages and control immune dysregulation in the TME.","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"5 2","pages":"249-258"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11308798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141908532","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}

引用次数: 0

G protein-coupled receptors: a gateway to targeting oncogenic EVs? G 蛋白偶联受体：靶向致癌 EV 的通道？

Extracellular vesicles and circulating nucleic acids Pub Date : 2024-05-23 DOI: 10.20517/evcna.2024.10

Lotte Di Niro, Amber C. Linders, Thomas Glynn, D. M. Pegtel, M. Siderius, C. Crudden, Martine J. Smit

{"title":"G protein-coupled receptors: a gateway to targeting oncogenic EVs?","authors":"Lotte Di Niro, Amber C. Linders, Thomas Glynn, D. M. Pegtel, M. Siderius, C. Crudden, Martine J. Smit","doi":"10.20517/evcna.2024.10","DOIUrl":"https://doi.org/10.20517/evcna.2024.10","url":null,"abstract":"Dysregulated intercellular communication is a key feature driving cancer progression. Recently, extracellular vesicles (EVs) have added a new channel to this dense communication network. Despite solid evidence that EVs are central mediators of dysregulated signaling in onco-pathological settings, this has yet to be translated into clinically actionable strategies. The heterogeneity of EV cargo molecules, plasticity of biogenesis routes, and large overlap with their role in physiological communication, complicate a potential targeting strategy. However, recent work has linked EV biology to perhaps the \"most druggable\" proteins - G protein-coupled receptors (GPCRs). GPCR targeting accounts for ~60% of drugs in development and more than a third of all currently approved drugs, spanning almost all areas of medicine. Although several GPCRs have been linked to cancer initiation and progression, relatively few agents have made it into oncological regimes, suggesting that their potential is underexploited. Herein, we examine the molecular mechanisms linking GPCRs to EV communication in cancer settings. We propose that GPCRs hold potential in the search for EV-targeting in oncology.","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141105150","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}

引用次数: 0

Which casein micelle removal method is suitable for studies of human milk extracellular vesicles? A systematic comparison of four different treatments for casein depletion before extracellular vesicle isolation from human milk 哪种酪蛋白胶束去除方法适合人乳细胞外囊泡研究？系统比较从母乳中分离胞外囊泡前的四种不同酪蛋白去除处理方法

Extracellular vesicles and circulating nucleic acids Pub Date : 2024-05-22 DOI: 10.20517/evcna.2024.02

Hatice Cetinkaya, Supasek Kongsomros, Laurie Nommsen-Rivers, Ardythe L. Morrow, S. Chutipongtanate

{"title":"Which casein micelle removal method is suitable for studies of human milk extracellular vesicles? A systematic comparison of four different treatments for casein depletion before extracellular vesicle isolation from human milk","authors":"Hatice Cetinkaya, Supasek Kongsomros, Laurie Nommsen-Rivers, Ardythe L. Morrow, S. Chutipongtanate","doi":"10.20517/evcna.2024.02","DOIUrl":"https://doi.org/10.20517/evcna.2024.02","url":null,"abstract":"Aim: This study aimed to systematically compare four casein micelle removal methods on the particle and protein characteristics of the isolated human milk EVs.\u0000 Methods: The defatted milk was treated with 1% sodium citrate, 20 mM ethylenediaminetetraacetic acid (EDTA), 1% acetic acid, or 1% chymosin/calcium chloride for 30 min at 4 °C to remove casein micelles. EV isolation was performed using qEV size exclusion chromatography. Milk turbidity at the optical density 350 nm and dot immunoblot with casein antibody were applied to monitor the qEV fractions. Particle analyses were performed using transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). The enrichment of human milk EV markers, i.e., tetraspanins, Alix, lactadherin, butyrophilin, and xanthine dehydrogenase, and casein depletion capabilities were evaluated by proteomics and immunoblotting.\u0000 Results: Compared to the untreated condition, sodium citrate and EDTA decreased milk turbidity by disrupting casein micelles, while acetic acid and chymosin removed them by inducing precipitation/coagulation. All treatments shifted casein immunoreactivity in the qEV fractions from large micelles (the exclusion volume) to small molecular sizes (gel-infiltrated fractions). Acidification affected human milk EV morphology, while EDTA, acetic acid, and chymosin methods slightly altered EV particle numbers. Different casein micelle removal methods confer different degrees of human milk EV marker enrichment and casein depletion. The method performances could be ranked as follows: chymosin > EDTA > acetic acid > sodium citrate.\u0000 Conclusion: Our findings suggest that chymosin and EDTA should be considered as the method of choice for casein micelle removal in future studies involving human milk EV isolation and characterization.","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"17 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141112638","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}

引用次数: 0

Hollow fiber bioreactor allows sustained production of immortalized mesenchymal stromal cell-derived extracellular vesicles 中空纤维生物反应器可持续生产永生化间充质基质细胞衍生的细胞外囊泡

Extracellular vesicles and circulating nucleic acids Pub Date : 2024-05-14 DOI: 10.20517/evcna.2023.76

Sergio G Garcia, Marta Sanroque-Muñoz, Marta Clos-Sansalvador, Miriam Font-Morón, M. Monguió-Tortajada, F. Borràs, Marcella Franquesa

{"title":"Hollow fiber bioreactor allows sustained production of immortalized mesenchymal stromal cell-derived extracellular vesicles","authors":"Sergio G Garcia, Marta Sanroque-Muñoz, Marta Clos-Sansalvador, Miriam Font-Morón, M. Monguió-Tortajada, F. Borràs, Marcella Franquesa","doi":"10.20517/evcna.2023.76","DOIUrl":"https://doi.org/10.20517/evcna.2023.76","url":null,"abstract":"Aim: Mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) have been reported to hold great potential as cell-free therapies due to their low immunogenicity and minimal toxicity. However, the large doses of MSC-EVs that are required for their clinical application highlight the urgency of finding a large-scale system for MSC-EV manufacture. In this study, we aimed to set up a hollow fiber bioreactor system for the continuous homogenous production of functional and high-quality MSC-EVs.\u0000 Methods: MSC lines from two donors were immortalized (iMSC) and inoculated into hollow fiber bioreactors. Throughout 4 weeks, conditioned medium was daily harvested. iMSC-EVs were purified and characterized for content, immunophenotype, size, and functionality and compared to 2D cultured iMSC.\u0000 Results: The iMSC inoculated into the bioreactor remained viable during the whole culture period, and they maintained their MSC phenotype at the end of EV production. Our results showed that the bioreactor system allows to obtain 3D-cultured iMSC-derived EVs (3D-EVs) that are comparable to flask (2D)-cultured iMSC-derived EVs (2D-EVs) in terms of protein and lipid content, size, and phenotype. We also confirm that 3D-derived EVs exhibit comparable functionality to 2D-EVs, showing pro-angiogenic potential in a dose-dependent manner.\u0000 Conclusions: These findings suggest that setting up a hollow fiber bioreactor system inoculating immortalized MSC lines facilitates the large-scale, functional, and high-quality production of iMSC-EVs. Our results emphasize the great potential of this production methodology to standardize EV production in the pursuit of clinical applications.","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"51 14","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140980791","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}

引用次数: 0