Extracellular vesicle最新文献

{"title":"A multi-organ, feto-maternal interface organ-on-chip, models pregnancy pathology and is a useful preclinical extracellular vesicle drug trial platform","authors":"Melody Safarzadeh ,&nbsp;Lauren S. Richardson ,&nbsp;Ananth Kumar Kammala ,&nbsp;Angela Mosebarger ,&nbsp;Mohamed Bettayeb ,&nbsp;Sungjin Kim ,&nbsp;Po Yi Lam ,&nbsp;Enkhtuya Radnaa ,&nbsp;Arum Han ,&nbsp;Ramkumar Menon","doi":"10.1016/j.vesic.2024.100035","DOIUrl":"https://doi.org/10.1016/j.vesic.2024.100035","url":null,"abstract":"<div><p>Pregnant women and their fetuses are often excluded from clinical trials due to missing drug-related pre-clinical trial information at the human feto-maternal interface (FMi). The two interfaces-placenta/decidua and fetal membranes/decidua are gatekeepers of drug transport; however, testing their functions is impractical during pregnancy. Limitations of current <em>in-vivo</em>/<em>in-vitro</em> models have hampered drug development and testing during pregnancy. Hence, major complications like preterm births and maternal and neonatal mortalities remain high. Advancements in organ-on-chip (OOC) platforms to test drug kinetics and efficacy and novel extracellular vesicle-based fetal drug delivery are expected to accelerate preclinical trials related to pregnancy complications. Here we report the development and testing of a humanized multi-organ fetal membrane/placenta (fetal)-decidua (maternal) interface OOC (FMi-PLA-OOC) that contains seven cell types interconnected through microchannels to maintain intercellular interactions as seen <em>in-utero</em>. Cytotoxicity, propagation, mechanism of action, and efficacy of engineered extracellular vesicles containing anti-inflammatory interleukin (IL)-10 (eIL-10) were evaluated to reduce FMi inflammation associated with preterm birth. A healthy and disease model (lipopolysaccharide-infectious inflammation) of the FMi-PLA-OOC was created and co-treated with eIL-10. eIL-10 propagated from the maternal to fetal side within 72-h, localized in all cell types, showed no cytotoxicity, activated IL-10 signaling pathways, and reduced lipopolysaccharide-induced inflammation (minimized NF-kB activation and proinflammatory cytokine production). These data recapitulated eIL-10s’ ability to reduce inflammation and delay infection-associated preterm birth in mouse models, suggesting FMi-PLA-OOC as an alternative approach to using animal models. Additionally, we report the utility of eIL-10 that can traverse through FMis to reduce inflammation-associated pregnancy complications.</p></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"3 ","pages":"Article 100035"},"PeriodicalIF":0.0,"publicationDate":"2024-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773041724000027/pdfft?md5=63caf11b5cb6a26a47eac9627586afec&pid=1-s2.0-S2773041724000027-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139935906","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 simple scalable extracellular vesicle isolation method using polyethylenimine polymers for use in cellular delivery","authors":"Marie Ange Djeungoue Petga ,&nbsp;Catherine Taylor ,&nbsp;Alexander Macpherson ,&nbsp;Surendar Reddy Dhadi ,&nbsp;Thomas Rollin ,&nbsp;Jeremy W. Roy ,&nbsp;Anirban Ghosh ,&nbsp;Stephen M. Lewis ,&nbsp;Rodney J. Ouellette","doi":"10.1016/j.vesic.2023.100033","DOIUrl":"https://doi.org/10.1016/j.vesic.2023.100033","url":null,"abstract":"<div><p>Extracellular vesicles (EVs) are gaining interest as efficient, biocompatible vehicles for cellular delivery of therapeutic cargo. Precipitation-based methods for the isolation of EVs remain popular due to ease of use and lack of requirements for specialized equipment. We describe here a novel charge-based EV isolation method that is simple, scalable, and uses inexpensive polyethylenimine (PEI) polymers. GFP-expressing EVs were isolated from the conditioned cell culture (CCM) media of HEK293-GFP cells using either branched 10 kDa PEI (B-PEI) or linear 25 kDa PEI (L-PEI). Isolated EVs were characterized by Western blotting, nanoparticle tracking analysis, transmission electron microscopy (TEM), and flow cytometry. Western blotting for common EV markers, including CD63, CD9, flotillin-1, and heat shock protein 70 were positive, while GRP94, a marker for cellular contamination, was negative. Isolated EVs had a mean diameter of 146 nm for B-PEI and 175 nm for L-PEI, while TEM revealed a spherical cup-shaped appearance typical of EVs. In addition, we determined that PEI-based EV isolation methods were scalable up to volumes of at least 50 mL. EVs isolated from CCM collected from SUM159 cells that express CD63 fused to a dual EGFP-Renilla-split tag were tested for their ability to reconstitute functional luciferase by delivering the CD63-EGFP-Renilla-split tag to SUM159 recipient cells loaded with a cytopermeable Renilla luciferase substrate. Although EVs isolated using L-PEI behaved similarly to EVs isolated using ultracentrifugation, we observed that EVs isolated using B-PEI produced a more rapid uptake and delivery of active luciferase. In this study we demonstrate that both branched and linear PEI polymers can precipitate EVs from CCM. Furthermore, once eluted from the polymers, the isolated EVs were able to deliver functional protein cargo to recipient cells. Overall, our data support PEI-based isolation of EVs as a simple, rapid method for the recovery of functional EVs.</p></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"3 ","pages":"Article 100033"},"PeriodicalIF":0.0,"publicationDate":"2024-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773041723000124/pdfft?md5=c7feb4086e774e807af0d19f7fcc7a6f&pid=1-s2.0-S2773041723000124-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139504234","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":"Exosome as drug delivery system: Current advancements","authors":"Vriti Sharma,&nbsp;Chitrangada Das Mukhopadhyay","doi":"10.1016/j.vesic.2023.100032","DOIUrl":"https://doi.org/10.1016/j.vesic.2023.100032","url":null,"abstract":"<div><p>Exosomes are nanovesicles released from cells due to pathophysiological events. These nanoparticles are resistant to metabolic destruction and can transcend the blood-brain barrier. Exosome therapy could be employed as precision medicine by targeting the underlying etiology. This article briefly elucidates the basic physiology of exosomes, their types, characteristics, and cargo that are employed for drug administration. It then delves into their therapeutic applications, such as oncology, neurological disorders, and regenerative medicine. Exosome-based therapeutic drug delivery using small molecules, nucleic acids, and proteins is also demonstrated. Finally, global organizations that are successfully creating and testing medicinal biomaterials are highlighted.</p></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"3 ","pages":"Article 100032"},"PeriodicalIF":0.0,"publicationDate":"2023-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773041723000112/pdfft?md5=bc07b912724cf64d2cf154fdff8a0200&pid=1-s2.0-S2773041723000112-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138558633","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":"Current challenges surrounding exosome treatments.","authors":"Eileen Tzng, Nathan Bayardo, Phillip C Yang","doi":"10.1016/j.vesic.2023.100023","DOIUrl":"10.1016/j.vesic.2023.100023","url":null,"abstract":"<p><p>Cardiovascular disease is the leading cause of death worldwide today and numerous studies are demonstrating that exosomes improve cardiac function after myocardial injury through various mechanisms. Exosome therapy has great potential as an effective precision medicine biologic by targeting the underlying disease process. However, this innovative approach may face some challenges, such as zeta potential, standardization of exosome collection, biopharmaceutical regulation, and more importantly, specific clinical application of exosome therapy. These issues will be addressed by broadly summarizing the biological plausibility; delivery, dosing, and pharmacokinetics; and reproducibility and manufacturing with a focus on microRNA as molecular cargo.</p>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"1 1","pages":"100023"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11870656/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"55274834","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":"CD63-snorkel tagging for isolation of exosomes","authors":"Chaoshan Han ,&nbsp;Junjie Yang ,&nbsp;Tingting Yin ,&nbsp;Junqing An ,&nbsp;Aijun Qiao ,&nbsp;Yangpo Cao ,&nbsp;Yuliang Feng ,&nbsp;Haocheng Lu ,&nbsp;Ying Wang ,&nbsp;Liang Yang ,&nbsp;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}

{"title":"Exomap1 mouse: A transgenic model for in vivo studies of exosome biology","authors":"Francis K. Fordjour ,&nbsp;Sarah Abuelreich ,&nbsp;Xiaoman Hong ,&nbsp;Emeli Chatterjee ,&nbsp;Valeria Lallai ,&nbsp;Martin Ng ,&nbsp;Andras Saftics ,&nbsp;Fengyan Deng ,&nbsp;Natacha Carnel-Amar ,&nbsp;Hiroaki Wakimoto ,&nbsp;Kazuhide Shimizu ,&nbsp;Malia Bautista ,&nbsp;Tuan Anh Phu ,&nbsp;Ngan K. Vu ,&nbsp;Paige C. Geiger ,&nbsp;Robert L. Raffai ,&nbsp;Christie D. Fowler ,&nbsp;Saumya Das ,&nbsp;Lane K. Christenson ,&nbsp;Tijana Jovanovic-Talisman ,&nbsp;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 ,&nbsp;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}

{"title":"Arrestin domain-containing protein 1-mediated microvesicles (ARMMs) protect against cadmium-induced neurotoxicity","authors":"Zunwei Chen ,&nbsp;Zhi Qiao ,&nbsp;Charlotte R. Wirth ,&nbsp;Hae-Ryung Park ,&nbsp;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}

{"title":"Expanding the horizon of EV-RNAs: LncRNAs in EVs as biomarkers for disease pathways","authors":"Michail Spanos ,&nbsp;Priyanka Gokulnath ,&nbsp;Emeli Chatterjee ,&nbsp;Guoping Li ,&nbsp;Dimitrios Varrias ,&nbsp;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}

{"title":"Current challenges surrounding exosome treatments","authors":"Eileen Tzng,&nbsp;Nathan Bayardo,&nbsp;Phillip C. Yang","doi":"10.1016/j.vesic.2023.100023","DOIUrl":"https://doi.org/10.1016/j.vesic.2023.100023","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":"49857396","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}