Extracellular vesicles and circulating nucleic acids最新文献

{"title":"Does the interplay between human endogenous retrovirus K and extracellular vesicles contribute to aging?","authors":"Catherine DeMarino, Avindra Nath, Zhengping Zhuang, Tara T. Doucet-O’Hare","doi":"10.20517/evcna.2023.45","DOIUrl":"https://doi.org/10.20517/evcna.2023.45","url":null,"abstract":"The role of extracellular vesicles (EVs), including retroviral-like particles (RVLPs), in pathogenic processes is currently a subject of active investigation. Several studies have identified mechanistic links between the increased presence of EVs and the process of senescence. A recent study reveals that the reverse transcribed complementary DNA (cDNA) of a human endogenous retroviral sequence can activate the innate immune system and result in tissue damage and/or the spread of cellular senescence to distant tissues. Several studies have linked EVs to age-related diseases, such as Alzheimer’s disease and Parkinson’s disease, and have included isolation of EVs from individuals with these diseases. Loss of epigenetic regulation, immune activation, and environmental stimuli can all lead to the expression of endogenous retroviruses and the incorporation of their proteins and transcripts into EVs. In addition, EVs disseminating these endogenous retroviral components have now been shown to act in a paracrine manner in multiple human diseases. Further investigation of the connection between EVs containing endogenous retroviral protein products or nucleotides should be pursued in models of age-related diseases.","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136159434","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":"Hepatocellular carcinoma cell-derived small extracellular vesicle-associated CD147 serves as a diagnostic marker and promotes endothelial cell angiogenesis via the PI3K/Akt pathway","authors":"De-Fa Huang, Wen-Juan Zhang, Jie Chen, Zhi-Gang Jiao, Xiao-Ling Wang, Ding-Yu Rao, Wei-Song Li, Die Hu, Fang-Fang Xie, Xiao-Xing Wang, Zheng-Zhe Li, Xiao-Mei Yi, Ji-Yang Wu, Yu Jiang, Qi Wang, Tian-Yu Zhong","doi":"10.20517/evcna.2023.30","DOIUrl":"https://doi.org/10.20517/evcna.2023.30","url":null,"abstract":"Aim: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. The process of HCC development is closely related to angiogenesis. Plasma exosomes have diagnostic value in many diseases and have become a current research hotspot. We aimed to identify a key molecule in small extracellular vesicles (sEVs) involved in angiogenesis as a diagnostic marker for HCC and uncover the mechanism underlying its regulation in the angiogenesis process. Methods: Nano‐flow cytometer (nFCM) was used to detect CD147 expression in plasma-derived sEVs in 155 HCC patients, 59 liver cirrhosis (LC), and 82 healthy donors (HD). The mechanism of hepatocellular carcinoma cell-derived sEVs CD147 promoting angiogenesis was elucidated by cell proliferation assay, scratch wound healing assay, transwell assay, tube formation assay, and in vivo Matrigel plug angiogenesis assay. Results: We found that CD147 expression was significantly higher in HCC tissue samples than in normal tissues. We also found a significantly larger number of CD147-positive small extracellular vesicles (CD147+ sEVs) in the plasma of HCC patients than LC patients and HD. Furthermore, we showed that hepatocellular carcinoma cell (HepG2)-derived CD147+ sEVs promoted cell proliferation, migration, invasion, and angiogenesis in human umbilical vein endothelial cells. The CD147+ sEVs upregulated vascular endothelial growth factor A (VEGFA) by activating the PI3K/Akt pathway, thereby promoting angiogenesis. Conclusion: HCC-derived sEVs-associated CD147 serves as a diagnostic marker and promotes endothelial cell angiogenesis via the PI3K/Akt pathway.","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135923776","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":"Conference report for the 2nd annual American Society for Intercellular Communication (ASIC) meeting, 2022.","authors":"Ashley E Russell, Michael W Graner, Shilpa Buch","doi":"10.20517/evcna.2022.43","DOIUrl":"10.20517/evcna.2022.43","url":null,"abstract":"on the role of EVs in inflammation and cardiovascular disease (CVD) during HIV infection. Rates of CVD in people living with HIV (PLWH) tend to be higher than in the uninfected population","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10568996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41222066","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":"Milk-borne small extracellular vesicles: kinetics and mechanisms of transport, distribution, and elimination.","authors":"Alice Ngu, Javaria Munir, Janos Zempleni","doi":"10.20517/evcna.2023.25","DOIUrl":"10.20517/evcna.2023.25","url":null,"abstract":"<p><p>Small extracellular vesicles (sEVs) in milk have the qualities desired for delivering therapeutics to diseased tissues. The production of bovine milk sEVs is scalable (10²¹ annually per cow), and they resist degradation in the gastrointestinal tract. Most cells studied to date internalize milk sEVs by a saturable process that follows Michaelis-Menten kinetics. The bioavailability of oral milk sEVs is approximately 50%. In addition to crossing the intestinal mucosa, milk sEVs also cross barriers such as the placenta and blood-brain barrier, thereby enabling the delivery of therapeutics to hard-to-reach tissues. In time course studies, levels of milk sEVs peaked in the intestinal mucosa, plasma, and urine approximately 6 h and returned to baseline 24 h after oral gavage in mice. In tissues, milk sEV levels peaked 12 h after gavage. Milk sEVs appear to be biologically safe. No cytokine storm was observed when milk sEVs were added to cultures of human peripheral blood mononuclear cells or administered orally to rats. Liver and kidney function and erythropoiesis were not impaired when milk sEVs were administered to rats by oral gavage for up to 15 days. Protocols for loading milk sEVs with therapeutic cargo are available. Currently, the use of milk sEVs (and other nanoparticles) in the delivery of therapeutics is limited by their rapid elimination through internalization by macrophages and lysosomal degradation in target cells. This mini review discusses the current knowledge base of sEV tissue distribution, excretion in feces and urine, internalization by macrophages, and degradation in lysosomes.</p>","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10568984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41222067","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 and particles as mediators of long-range communication in cancer: connecting biological function to clinical applications.","authors":"Tetsuhiko Asao, Gabriel Cardial Tobias, Serena Lucotti, David R Jones, Irina Matei, David Lyden","doi":"10.20517/evcna.2023.37","DOIUrl":"10.20517/evcna.2023.37","url":null,"abstract":"<p><p>Over the past decade, extracellular vesicles and particles (EVPs) have emerged as critical mediators of intercellular communication, participating in numerous physiological and pathological processes. In the context of cancer, EVPs exert local effects, such as increased invasiveness, motility, and reprogramming of tumor stroma, as well as systemic effects, including pre-metastatic niche formation, determining organotropism, promoting metastasis and altering the homeostasis of various organs and systems, such as the liver, muscle, and circulatory system. This review provides an overview of the critical advances in EVP research during the past decade, highlighting the heterogeneity of EVPs, their roles in intercellular communication, cancer progression, and metastasis. Moreover, the clinical potential of systemic EVPs as useful cancer biomarkers and therapeutic agents is explored. Last but not least, the progress in EVP analysis technologies that have facilitated these discoveries is discussed, which may further propel EVP research in the future.</p>","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11067132/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77401475","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: cross-organismal RNA trafficking in plants, microbes, and mammalian cells.","authors":"Qiang Cai,&nbsp;Lida Halilovic,&nbsp;Ting Shi,&nbsp;Angela Chen,&nbsp;Baoye He,&nbsp;Huaitong Wu,&nbsp;Hailing Jin","doi":"10.20517/evcna.2023.10","DOIUrl":"https://doi.org/10.20517/evcna.2023.10","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) are membrane-enclosed nanometer-scale particles that transport biological materials such as RNAs, proteins, and metabolites. EVs have been discovered in nearly all kingdoms of life as a form of cellular communication across different cells and between interacting organisms. EV research has primarily focused on EV-mediated intra-organismal transport in mammals, which has led to the characterization of a plethora of EV contents from diverse cell types with distinct and impactful physiological effects. In contrast, research into EV-mediated transport in plants has focused on inter-organismal interactions between plants and interacting microbes. However, the overall molecular content and functions of plant and microbial EVs remain largely unknown. Recent studies into the plant-pathogen interface have demonstrated that plants produce and secrete EVs that transport small RNAs into pathogen cells to silence virulence-related genes. Plant-interacting microbes such as bacteria and fungi also secrete EVs which transport proteins, metabolites, and potentially RNAs into plant cells to enhance their virulence. This review will focus on recent advances in EV-mediated communications in plant-pathogen interactions compared to the current state of knowledge of mammalian EV capabilities and highlight the role of EVs in cross-kingdom RNA interference.</p>","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10419970/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10008221","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":"Emerging connections between GPI-anchored proteins and their extracellular carriers in colorectal cancer.","authors":"Oleg S Tutanov, Sarah E Glass, Robert J Coffey","doi":"10.20517/evcna.2023.17","DOIUrl":"10.20517/evcna.2023.17","url":null,"abstract":"<p><p>Although extracellular vesicles (EVs) were discovered over 40 years ago, there has been a resurgence of interest in secreted vesicles and their attendant cargo as novel modes of intracellular communication. In addition to vesicles, two amembranous nanoparticles, exomeres and supermeres, have been isolated and characterized recently. In this rapidly expanding field, it has been challenging to assign cargo and specific functions to a particular carrier. Refinement of isolation methods, well-controlled studies, and guidelines detailed by Minimal Information for Studies of Extracellular Vesicles (MISEV) are being employed to \"bring order to chaos.\" In this review, we will briefly summarize three types of extracellular carriers - small EVs (sEVs), exomeres, and supermeres - in the context of colorectal cancer (CRC). We found that a number of GPI-anchored proteins (GPI-APs) are overexpressed in CRC, are enriched in exosomes (a distinct subset of sEVs), and can be detected in exomeres and supermeres. This affords the opportunity to elaborate on GPI-AP biogenesis, modifications, and trafficking using DPEP1, a GPI-AP upregulated in CRC, as a prime example. We have cataloged the GPI-anchored proteins secreted in CRC and will highlight features of select CRC-associated GPI-anchored proteins we have detected. Finally, we will discuss the remaining challenges and future opportunities in studying these secreted GPI-APs in CRC.</p>","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10569057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41241734","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 in the treatment and prevention of osteoarthritis: can horses help us translate this therapy to humans?","authors":"Thomas J O'Brien, Fiona Hollinshead, Laurie R Goodrich","doi":"10.20517/evcna.2023.11","DOIUrl":"10.20517/evcna.2023.11","url":null,"abstract":"<p><p>Osteoarthritis (OA) is a common joint disease affecting humans and horses, resulting in significant morbidity, financial expense, and loss of athletic use. While the pathogenesis is incompletely understood, inflammation is considered crucial in the development and progression of the disease. Mesenchymal stromal cells (MSCs) have received increasing scientific attention for their anti-inflammatory, immunomodulatory, and pro-regenerative effects. However, there are concerns about their ability to become a commercially available therapeutic. Extracellular vesicles (EVs) are now recognized to play a crucial role in the therapeutic efficacy observed with MSCs and offer a potentially novel cell-free therapeutic that may negate many of the concerns with MSCs. There is evidence that EVs have profound anti-inflammatory, immunomodulatory, and pro-regenerative effects equal to or greater than the MSCs they are derived from in the treatment of OA. Most of these studies are in small animal models, limiting the translation of these results to humans. However, highly translational animal models are crucial for further understanding the efficacy of potential therapeutics and for close comparisons with humans. For this reason, the horse, which experiences the same gravitational impacts on joints similar to people, is a highly relevant large animal species for testing. The equine species has well-designed and validated OA models, and additionally, therapies can be further tested in naturally occurring OA to validate preclinical model testing. Therefore, the horse is a highly suitable model to increase our knowledge of the therapeutic potential of EVs.</p>","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10568983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41222065","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":"Synaptic proteins in neuron-derived extracellular vesicles as biomarkers for Alzheimer's disease: novel methodology and clinical proof of concept.","authors":"Erez Eitan, Tricia Thornton-Wells, Katya Elgart, Eren Erden, Eve Gershun, Amir Levine, Olga Volpert, Mitra Azadeh, Daniel G Smith, Dimitrios Kapogiannis","doi":"10.20517/evcna.2023.13","DOIUrl":"10.20517/evcna.2023.13","url":null,"abstract":"<p><strong>Aims: </strong>Blood biomarkers can improve drug development for Alzheimer's disease (AD) and its treatment. Neuron-derived extracellular vesicles (NDEVs) in plasma offer a minimally invasive platform for developing novel biomarkers that may be used to monitor the diverse pathogenic processes involved in AD. However, NDEVs comprise only a minor fraction of circulating extracellular vesicles (EVs). Most published studies have leveraged the L1 cell adhesion molecule (L1CAM) for NDEV immunocapture. We aimed to develop and optimize an alternative, highly specific immunoaffinity method to enrich blood NDEVs for biomarker development.</p><p><strong>Methods: </strong>After screening multiple neuronal antigens, we achieved NDEV capture with high affinity and specificity using antibodies against Growth-Associated Protein (GAP) 43 and Neuroligin 3 (NLGN3). The EV identity of the captured material was confirmed by electron microscopy, western blotting, and proteomics. The specificity for neuronal origin was demonstrated by showing enrichment for neuronal markers (proteins, mRNA) and recovery of spiked neuronal EVs. We performed NDEV isolation retrospectively from plasma samples from two cohorts of early AD patients (N = 19 and N = 40) and controls (N = 20 and N = 19) and measured p181-Tau, amyloid-beta (Aβ) 42, brain-derived neurotrophic factor (BDNF), precursor brain-derived neurotrophic factor (proBDNF), glutamate receptor 2 (GluR2), postsynaptic density protein (PSD) 95, GAP43, and syntaxin-1.</p><p><strong>Results: </strong>p181-Tau, Aβ42, and NRGN were elevated in AD samples, whereas proBDNF, GluR2, PSD95, GAP43, and Syntaxin-1 were reduced. Differences for p181-Tau, proBDNF, and GluR2 survived multiple-comparison correction and were correlated with cognitive scores. A model incorporating biomarkers correctly classified 94.7% of AD participants and 61.5% of control participants. The observed differences in NDEVs-associated biomarkers are consistent with previous findings.</p><p><strong>Conclusion: </strong>NDEV isolation by GAP43 and NLGN3 immunocapture offers a robust novel platform for biomarker development in AD, suitable for large-scale validation.</p>","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10568955/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41241735","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 from the CNS play pivotal roles in neuroprotection and neurodegeneration: lessons from <i>in vitro</i> experiments.","authors":"Isaac Colvett, Hannah Saternos, Christina Coughlan, Anne Vielle, Aurélie Ledreux","doi":"10.20517/evcna.2023.07","DOIUrl":"10.20517/evcna.2023.07","url":null,"abstract":"<p><p>Intercellular communication between diverse cell types is crucial for the maintenance of the central nervous system, and exosomes have been shown to play an important role in this process. Exosomes are small extracellular vesicles (EVs) that are released by all cell types and carry cargoes that can elicit downstream effects in recipient cells. Exosomal communication in the central nervous system has been implicated in many neurodegenerative diseases, ranging from Alzheimer's disease to major depressive disorder. Though there remain many unknowns in the field of EV biology, <i>in vitro</i> experiments can provide many insights into their potential roles in health and disease. In this review, we discuss the findings of many <i>in vitro</i> EV experiments, with a focus on the potential roles in regulating cell viability, inflammation, oxidative stress, and neurite integrity in the central nervous system.</p>","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10586524/pdf/nihms-1892021.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49685738","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}