Chaoshan Han , Junjie Yang , Tingting Yin , Junqing An , Aijun Qiao , Yangpo Cao , Yuliang Feng , Haocheng Lu , Ying Wang , Liang Yang , Gangjian Qin
{"title":"CD63-snorkel tagging for isolation of exosomes","authors":"Chaoshan Han , Junjie Yang , Tingting Yin , Junqing An , Aijun Qiao , Yangpo Cao , Yuliang Feng , Haocheng Lu , Ying Wang , Liang Yang , Gangjian Qin","doi":"10.1016/j.vesic.2023.100031","DOIUrl":"https://doi.org/10.1016/j.vesic.2023.100031","url":null,"abstract":"<div><p>Exosomes (Exo) are important mediators of inter-cellular communications; however, no effective method is available for isolating, thus characterizing, cellular-specific exosomes <em>in vivo</em>. Since CD63 is a reliable marker for exosomes, we have developed a tagging strategy, term “CD63-Snorkel (CD63-SNKL)”, in which CD63 at its intracellular C-terminus was fused to a fragment of PDGFRB that contains the transmembrane domain tethered to multiple epitope tags (HA, His, and FLAG) displayed in tandem on surface. We found that the CD63-SNKL protein has similar subcellular localizations as endogenous CD63 and can be effectively sorted into Exo. Furthermore, Exo secreted from CD63-SNKL–transduced cells can be effectively captured on anti-HA magnetic beads and eluted with HA peptides. Thus, CD63-SNKL may be engineered for isolating and tracking endogenous tissue-specific Exo <em>in vivo</em>.</p></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"2 ","pages":"Article 100031"},"PeriodicalIF":0.0,"publicationDate":"2023-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773041723000100/pdfft?md5=4118b6e1865381af9c561c620692b519&pid=1-s2.0-S2773041723000100-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92099123","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}
Francis K. Fordjour , Sarah Abuelreich , Xiaoman Hong , Emeli Chatterjee , Valeria Lallai , Martin Ng , Andras Saftics , Fengyan Deng , Natacha Carnel-Amar , Hiroaki Wakimoto , Kazuhide Shimizu , Malia Bautista , Tuan Anh Phu , Ngan K. Vu , Paige C. Geiger , Robert L. Raffai , Christie D. Fowler , Saumya Das , Lane K. Christenson , Tijana Jovanovic-Talisman , Stephen J. Gould
{"title":"Exomap1 mouse: A transgenic model for in vivo studies of exosome biology","authors":"Francis K. Fordjour , Sarah Abuelreich , Xiaoman Hong , Emeli Chatterjee , Valeria Lallai , Martin Ng , Andras Saftics , Fengyan Deng , Natacha Carnel-Amar , Hiroaki Wakimoto , Kazuhide Shimizu , Malia Bautista , Tuan Anh Phu , Ngan K. Vu , Paige C. Geiger , Robert L. Raffai , Christie D. Fowler , Saumya Das , Lane K. Christenson , Tijana Jovanovic-Talisman , Stephen J. Gould","doi":"10.1016/j.vesic.2023.100030","DOIUrl":"https://doi.org/10.1016/j.vesic.2023.100030","url":null,"abstract":"<div><p>Exosomes are small extracellular vesicles (sEVs) of ∼30–150 nm in diameter that are enriched in exosome marker proteins and play important roles in health and disease. To address large unanswered questions regarding exosome biology <em>in vivo</em>, we created the Exomap1 transgenic mouse, which in response to Cre recombinase expresses the most highly enriched exosomal marker protein known, human CD81, fused to mNeonGreen (HsCD81mNG), and prior to Cre expresses a mitochondrial red fluorescent protein. Validation of the <em>exomap1</em> mouse with eight distinct Cre drivers demonstrated that HsCD81mNG was expressed only in response to Cre, that murine cells correctly localized HsCD81mNG to the plasma membrane, and that this led to the secretion of HsCD81mNG in EVs that had the size (∼70–80 nm), topology, and composition of exosomes. Furthermore, cell type-specific activation of the <em>exomap1</em> transgene allowed us to use quantitative single molecule localization microscopy to calculate the cell type-specific contribution to biofluid exosome populations. Specifically, we show that neurons contribute ∼1% to plasma and cerebrospinal fluid exosome populations whereas hepatocytes contribute ∼15% to plasma exosome populations, numbers that reflect the known vascular permeabilities of brain and liver. These observations validate the use of Exomap1 mouse models for <em>in vivo</em> studies of exosome biology.</p></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"2 ","pages":"Article 100030"},"PeriodicalIF":0.0,"publicationDate":"2023-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49857421","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":"Guidelines for clinical translation and commercialization of extracellular vesicles and exosomes based therapeutics","authors":"Ke Cheng , Raghu Kalluri","doi":"10.1016/j.vesic.2023.100029","DOIUrl":"https://doi.org/10.1016/j.vesic.2023.100029","url":null,"abstract":"<div><p>Extracellular vesicles (EVs) are lipid-bilayer delimited membrane structures released by cells, and play a role in intercell communication and disease development. The Global market for EVs in diagnostic and therapeutic applications is expanding. This review maps the current status of EV industry, summarizes the recent advances in EV manufacturing, and focuses on preclinical research involving EVs. The complexity and heterogeneity of EVs provide new opportunities for the development of clinical-grade EV products. The standardization of manufacturing and robust quality control must meet all the Food and Drug Administration requirements and expectations. We believe the evolution of EV research and their mass production with stringency will open a new era of EV-based products in the near future.</p></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"2 ","pages":"Article 100029"},"PeriodicalIF":0.0,"publicationDate":"2023-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49857422","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}
Zunwei Chen , Zhi Qiao , Charlotte R. Wirth , Hae-Ryung Park , Quan Lu
{"title":"Arrestin domain-containing protein 1-mediated microvesicles (ARMMs) protect against cadmium-induced neurotoxicity","authors":"Zunwei Chen , Zhi Qiao , Charlotte R. Wirth , Hae-Ryung Park , Quan Lu","doi":"10.1016/j.vesic.2023.100027","DOIUrl":"10.1016/j.vesic.2023.100027","url":null,"abstract":"<div><p>Exposure to environmental heavy metals such as cadmium (Cd) is often linked to neurotoxicity but the underlying mechanisms remain poorly understood. Here we show that Arrestin domain-containing protein 1 (ARRDC1)-mediated microvesicles (ARMMs)–an important class of extracellular vesicles (EVs) whose biogenesis occurs at the plasma membrane–protect against Cd-induced neurotoxicity. Cd increased the production of EVs, including ARMMs, in a human neural progenitor cell line, ReNcell CX (ReN) cells. ReN cells that lack ARMMs production as a result of CRISPR-mediated <em>ARRDC1</em> knockout were more susceptible to Cd toxicity as evidenced by increased LDH production as well as elevated level of oxidative stress markers. Importantly, adding ARMMs back to the <em>ARRDC1</em>-knockout ReN cells significantly reduced Cd-induced toxicity. Consistent with this finding, proteomics data showed that anti-oxidative stress proteins are enriched in ARMMs secreted from ReN cells. Together our study reveals a novel protective role of ARMMs in Cd neurotoxicity and suggests that ARMMs may be used therapeutically to reduce neurotoxicity caused by exposure to Cd and potentially other metal toxicants.</p></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"2 ","pages":"Article 100027"},"PeriodicalIF":0.0,"publicationDate":"2023-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10443948/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10104454","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}
Michail Spanos , Priyanka Gokulnath , Emeli Chatterjee , Guoping Li , Dimitrios Varrias , Saumya Das
{"title":"Expanding the horizon of EV-RNAs: LncRNAs in EVs as biomarkers for disease pathways","authors":"Michail Spanos , Priyanka Gokulnath , Emeli Chatterjee , Guoping Li , Dimitrios Varrias , Saumya Das","doi":"10.1016/j.vesic.2023.100025","DOIUrl":"https://doi.org/10.1016/j.vesic.2023.100025","url":null,"abstract":"<div><p>Extracellular vesicles (EVs) are membrane-bound nanoparticles with different types of cargo released by cells and postulated to mediate functions such as intercellular communications. Recent studies have shown that long non-coding RNAs (lncRNAs) or their fragments are present as cargo within EVs. LncRNAs are a heterogeneous group of RNA species with a length exceeding 200 nucleotides with diverse functions in cells based on their localization. While lncRNAs are known for their important functions in cellular regulation, their presence and role in EVs have only recently been explored. While certain studies have observed EV-lncRNAs to be tissue- and disease-specific, it remains to be determined whether or not this is a global observation. Nonetheless, these molecules have demonstrated promising potential to serve as new diagnostic and prognostic biomarkers. In this review, we critically evaluate the role of EV-derived lncRNAs in several prevalent diseases, including cancer, cardiovascular diseases, and neurodegenerative diseases, with a specific focus on their role as biomarkers.</p></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"2 ","pages":"Article 100025"},"PeriodicalIF":0.0,"publicationDate":"2023-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49857394","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}
Kai Qiao , Xinyue Cui , Jiamin Gao , Fengyi Yu , Haohao Liu , Yichen Dai , Jiming Liu , Yu Yang , Xunde Xian , Jinming Hu , Junnan Tang , Xiaolin Cui
{"title":"Roles of extracellular vesicles derived from immune cells in atherosclerosis","authors":"Kai Qiao , Xinyue Cui , Jiamin Gao , Fengyi Yu , Haohao Liu , Yichen Dai , Jiming Liu , Yu Yang , Xunde Xian , Jinming Hu , Junnan Tang , Xiaolin Cui","doi":"10.1016/j.vesic.2023.100028","DOIUrl":"https://doi.org/10.1016/j.vesic.2023.100028","url":null,"abstract":"","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"2 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49857393","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":"Therapeutic and diagnostic potential of extracellular vesicles in amyotrophic lateral sclerosis","authors":"Taylor J. Ellison , Steven L. Stice , Yao Yao","doi":"10.1016/j.vesic.2022.100019","DOIUrl":"https://doi.org/10.1016/j.vesic.2022.100019","url":null,"abstract":"","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"2 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49857399","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}