{"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}
Yu Zhang , Weiliang Wu , Xiangbin Pan , Yanli Wang , Chengjie Wu , Lin Lu , Xi-Yong Yu , Yangxin Li
{"title":"Extracellular vesicles as novel therapeutic targets and diagnosis markers","authors":"Yu Zhang , Weiliang Wu , Xiangbin Pan , Yanli Wang , Chengjie Wu , Lin Lu , Xi-Yong Yu , Yangxin Li","doi":"10.1016/j.vesic.2022.100017","DOIUrl":"10.1016/j.vesic.2022.100017","url":null,"abstract":"<div><p>Extracellular vesicles (EVs) are membranous vesicles secreted from cells to the outside and are widely present in body fluids. The most commonly used method to isolate EVs is ultracentrifugation. EVs contain lipids, proteins, genetic material, and organelles, which can be used as communication carriers between different cells and potential disease biomarkers. EVs secreted by different cells (cancer cells, adipocytes, mesenchymal stem cells, immune cells et al.) play different functions. With the development of technology, EVs can also be engineered to deliver drugs. EVs also play an important role in the progression, prevention, diagnosis, and treatment of Corona Virus Disease 2019 (COVID-19).</p></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"1 ","pages":"Article 100017"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773041722000129/pdfft?md5=e27d3ccfc78e3fb048ad92d36880420a&pid=1-s2.0-S2773041722000129-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44174769","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}
Qiong Yang , Danyang Yue , Qian Ren , Guoqing Xia , Baihui Zhang , Yinyin Qin , Tianfei Ran , Min Wang , Li Pei , Jun Pan
{"title":"The interactions between extracellular vesicles and mesenchymal stem cells: Their potential roles in osteoarthritis development and cartilage repair","authors":"Qiong Yang , Danyang Yue , Qian Ren , Guoqing Xia , Baihui Zhang , Yinyin Qin , Tianfei Ran , Min Wang , Li Pei , Jun Pan","doi":"10.1016/j.vesic.2022.100011","DOIUrl":"10.1016/j.vesic.2022.100011","url":null,"abstract":"<div><p>Osteoarthritis (OA) is a chronic cartilage degeneration disease affecting total joint and with a wide global impact. Stem cell therapy has emerged as a potential stock for the treatment of OA. Exosomes are the mainstay of the paracrine function in stem cells, acting as an important mediator of intercellular communication. The purpose of this review is to sort out the close relationships among OA, MSCs, and exosomes. We find though majority of researches on exosomes focus on normal MSC-derived exosomes to restore tissues, studies demonstrate that OA or inflammation-induced microenvironment can alter exosomes, which in turn affect the biological behaviors and functions of receptor cells in the joint cavity, including proliferation and differentiation of MSCs. Exosomes, MSCs and OA form a triangular relationship. More future research directions are exploring the effects of OA-derived exosomes on chondrogenic differentiation of MSCs, especially on mitochondria to disclose the reasons for failure endogenous repair by MSCs, and normalizing the OA exosomes to treat OA.</p></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"1 ","pages":"Article 100011"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773041722000063/pdfft?md5=8eb8bca79abdb7597470a39e2db3d70e&pid=1-s2.0-S2773041722000063-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45112342","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}
Ramana Vaka , Sophie Van Remortel , Valentina Ly , Darryl R. Davis
{"title":"Extracellular vesicle therapy for non-ischemic heart failure: A systematic review of preclinical studies","authors":"Ramana Vaka , Sophie Van Remortel , Valentina Ly , Darryl R. Davis","doi":"10.1016/j.vesic.2022.100009","DOIUrl":"10.1016/j.vesic.2022.100009","url":null,"abstract":"<div><p>Cell-derived extracellular vesicles (EVs) are being actively explored as a novel acellular approach to heart failure. Accumulating evidence suggests EVs improve cardiac function in non-ischemic heart failure, but the strength and consistency of this effect is unknown. As such, we critically appraised the preclinical literature supporting the ability of EVs to improve cardiac function in animal models of non-ischemic heart failure. After a systematic search that yielded 18 studies, we determined the overall effect of EV treatment on left ventricular function and performed regression analysis to identify EV effects on clinically relevant parameters. EV treatment uniformly improved ejection fraction (2.41 [95% CI: 1.76, 3.06; p < 0.00001; I<sup>2</sup> = 46%]) and fractional shortening (2.22 [95% CI: 1.40, 3.05; p < 0.00001; I<sup>2</sup> = 56%]) as compared to untreated control animals. Secondary outcomes (such as left ventricular volumes or myocardial fibrosis) were similarly improved in EV treated animals. Although the number of studies included in the analysis was modest, there was no evidence for a publication bias. In conclusion, EV treatment improves cardiac function in preclinical models of non-ischemic heart failure. Although EVs originated from dissimilar cell lines and were applied to a variety of different animal models, we observed a consistent improvement in cardiac function suggesting application of EVs to non-ischemic heart failure has merit and warrants future attention.</p></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"1 ","pages":"Article 100009"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S277304172200004X/pdfft?md5=de9270248b05cc7b64de99fdf0488d78&pid=1-s2.0-S277304172200004X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43654404","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}
Amanda R. Haltom , Wafa E. Hassen , Janine Hensel , Jiha Kim , Hikaru Sugimoto , Bingrui Li , Kathleen M. McAndrews , Meagan R. Conner , Michelle L. Kirtley , Xin Luo , Bingqing Xie , Olga V. Volpert , Susan Olalekan , Natalia Maltsev , Anindita Basu , Valerie S. LeBleu , Raghu Kalluri
{"title":"Engineered exosomes targeting MYC reverse the proneural-mesenchymal transition and extend survival of glioblastoma","authors":"Amanda R. Haltom , Wafa E. Hassen , Janine Hensel , Jiha Kim , Hikaru Sugimoto , Bingrui Li , Kathleen M. McAndrews , Meagan R. Conner , Michelle L. Kirtley , Xin Luo , Bingqing Xie , Olga V. Volpert , Susan Olalekan , Natalia Maltsev , Anindita Basu , Valerie S. LeBleu , Raghu Kalluri","doi":"10.1016/j.vesic.2022.100014","DOIUrl":"10.1016/j.vesic.2022.100014","url":null,"abstract":"<div><p>Dysregulated Myc signaling is a key oncogenic pathway in glioblastoma multiforme (GBM). Yet, effective therapeutic targeting of Myc continues to be challenging. Here, we demonstrate that exosomes generated from human bone marrow mesenchymal stem cells (MSCs) engineered to encapsulate siRNAs targeting Myc (iExo-Myc) localize to orthotopic GBM tumors in mice. Treatment of late stage GBM tumors with iExo-Myc inhibits proliferation and angiogenesis, suppresses tumor growth, and extends survival. Transcriptional profiling of tumors reveals that the mesenchymal transition and estrogen receptor signaling pathways are impacted by Myc inhibition. Single nuclei RNA sequencing (snRNA-seq) shows that iExo-Myc treatment induces transcriptional repression of multiple growth factor and interleukin signaling pathways, triggering a mesenchymal to proneural transition and shifting the cellular landscape of the tumor. These data confirm that Myc is an effective anti-glioma target and that iExo-Myc offers a feasible, readily translational strategy to inhibit challenging oncogene targets for the treatment of brain tumors.</p></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"1 ","pages":"Article 100014"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10373511/pdf/nihms-1913722.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9893951","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}
Kristen D. Popowski , Blanca López de Juan Abad , Arianna George , Dylan Silkstone , Elizabeth Belcher , Jaewook Chung , Asma Ghodsi , Halle Lutz , Jada Davenport , Mallory Flanagan , Jorge Piedrahita , Phuong-Uyen C. Dinh , Ke Cheng
{"title":"Inhalable exosomes outperform liposomes as mRNA and protein drug carriers to the lung","authors":"Kristen D. Popowski , Blanca López de Juan Abad , Arianna George , Dylan Silkstone , Elizabeth Belcher , Jaewook Chung , Asma Ghodsi , Halle Lutz , Jada Davenport , Mallory Flanagan , Jorge Piedrahita , Phuong-Uyen C. Dinh , Ke Cheng","doi":"10.1016/j.vesic.2022.100002","DOIUrl":"10.1016/j.vesic.2022.100002","url":null,"abstract":"<div><p>Respiratory diseases are among the leading causes of morbidity and mortality worldwide, coupled with the ongoing coronavirus disease 2019 (COVID-19) pandemic. mRNA lipid nanoparticle (LNP) vaccines have been developed, but their intramuscular delivery limits pulmonary bioavailability. Inhalation of nanoparticle therapeutics offers localized drug delivery that minimizes off targeted adverse effects and has greater patient compliance. However, LNP platforms require extensive reformulation for inhaled delivery. Lung-derived extracellular vesicles (Lung-Exo) offer a biological nanoparticle alternative that is naturally optimized for mRNA translation and delivery to pulmonary cells. We compared the biodistribution of Lung-Exo against commercially standard biological extracellular vesicles (HEK-Exo) and LNPs (Lipo), where Lung-Exo exhibited superior mRNA and protein cargo distribution to and retention in the bronchioles and parenchyma following nebulization administration. This suggests that inhaled Lung-Exo can deliver mRNA and protein drugs with enhanced pulmonary bioavailability and therapeutic efficacy.</p></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"1 ","pages":"Article 100002"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9213043/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10287060","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}
Yi Wen , Qin Fu , Ashley Soliwoda , Sheng Zhang , Mingfeng Zheng , Wenjun Mao , Yuan Wan
{"title":"Cell-derived nanovesicles prepared by membrane extrusion are good substitutes for natural extracellular vesicles","authors":"Yi Wen , Qin Fu , Ashley Soliwoda , Sheng Zhang , Mingfeng Zheng , Wenjun Mao , Yuan Wan","doi":"10.1016/j.vesic.2022.100004","DOIUrl":"10.1016/j.vesic.2022.100004","url":null,"abstract":"<div><p>Extracellular vesicles (EV) as drug delivery nanocarriers are under intense investigation. Although clinical-grade EVs have been produced on a large-scale, low yield and high production costs of natural EVs (nEV) limit the relevant industrial translation. Recent studies show that mechanical extrusion of cells can generate nEV-like cell-derived nanovesicles (CNV) which can also be used as drug nanocarriers. Moreover, in comparison with nEVs, CNVs have similar physicochemical properties. Nevertheless, a comprehensive comparison of cargo between nEVs and CNVs has not been investigated yet. Therefore, the aim of this study is to profile and compare CNVs to nEVs. Our results show that no significant difference was found in size, morphology, and classical markers between nEVs and CNVs derived from MDA-MB-231 cells. Protein sequencing data reveals the similarity of membrane proteins between the two groups was <span><math><mo>∼</mo></math></span>71%, while it was <span><math><mo>∼</mo></math></span>21% when pertaining to total protein cargo. Notably, a high similarity of membrane proteins was also found between nEVs and CNVs derived from eight additional cancer cell lines. Moreover, analysis of the top 1000 small RNAs with RNA sequencing showed a <span><math><mo>∼</mo></math></span>65% similarity between the two groups. Altogether, we infer from the high similarity of membrane proteins and small RNA cargo that CNVs can be a good substitute for nEVs. In brief, our findings support previous studies with a notion that CNVs yield comparable performance with nEVs and could pave the way for clinical implementation of CNV-based therapeutics in the future.</p></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"1 ","pages":"Article 100004"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/77/95/nihms-1859360.PMC9794200.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10509824","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}
Sierra A. Walker , Irina Davidovich , Yubo Yang , Andrew Lai , Jenifer Pendiuk Goncalves , Vatsal Deliwala , Sara Busatto , Shane Shapiro , Na’ama Koifman , Carlos Salomon , Yeshayahu Talmon , Joy Wolfram
{"title":"Sucrose-based cryoprotective storage of extracellular vesicles","authors":"Sierra A. Walker , Irina Davidovich , Yubo Yang , Andrew Lai , Jenifer Pendiuk Goncalves , Vatsal Deliwala , Sara Busatto , Shane Shapiro , Na’ama Koifman , Carlos Salomon , Yeshayahu Talmon , Joy Wolfram","doi":"10.1016/j.vesic.2022.100016","DOIUrl":"10.1016/j.vesic.2022.100016","url":null,"abstract":"<div><p>Advancements in extracellular vesicle (EV) studies necessitate the development of optimized storage conditions to ensure preservation of physical and biochemical characteristics. In this study, the most common buffer for EV storage (phosphate-buffered saline/PBS) was compared to a cryoprotective 5% sucrose solution. The size distribution and concentration of EVs from two different sources changed to a greater extent after −80 °C storage in PBS compared to the sucrose solution. Additionally, molecular surface protrusions and transmembrane proteins were more prevalent in EVs stored in the sucrose solution compared to those stored in PBS. This study demonstrates, for the first time, that distinct ring-like molecular complexes and cristae-like folded membranous structures are visible upon EV degradation. Taken together, the size, concentration, molecular surface extensions, and transmembrane proteins of EVs varied substantially based on the buffer used for −80 °C storage, suggesting that biocompatible cryoprotectants, such as sucrose, should be considered for EV studies.</p></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"1 ","pages":"Article 100016"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773041722000117/pdfft?md5=86b94a603c3bfe47ab1d92a96499da88&pid=1-s2.0-S2773041722000117-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42655161","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}