Xuerui Chen , Liyun Zhu , Jianyun Liu , Yi Lu , Longlu Pan , Junjie Xiao
{"title":"Greasing wheels of cell-free therapies for cardiovascular diseases: Integrated devices of exosomes/exosome-like nanovectors with bioinspired materials","authors":"Xuerui Chen , Liyun Zhu , Jianyun Liu , Yi Lu , Longlu Pan , Junjie Xiao","doi":"10.1016/j.vesic.2022.100010","DOIUrl":"10.1016/j.vesic.2022.100010","url":null,"abstract":"<div><p>Mortality and morbidity of cardiovascular diseases (CVDs) including ischemic heart disease (IHD) and heart failure (HF) are arising worldwide. Once cardiomyocyte is impaired, it is challenging to regenerate which is largely limited by the irreversibility of cell cycle after birth. Emergent approaches in regenerative medicine head toward the application of extracellular vesicles (EVs) such as exosomes in next-generation cell-free treatment strategies for CVDs, attributed to their repair promotion. However, naked exosomes undergo major obstacles of high clearance by the mononuclear phagocyte system and transient retention of exosomes in transplanted areas, eventually failing in the endogenous repair. Strategies optimizing matrix materials to release exosomes in a targeted, sustained and minimally invasive manner will pave the way for empowering cardiac repair and regeneration. In this review, we extensively summarize the integrated devices of exosome or exosome-like nanovectors with biomaterials for treating CVDs. Furthermore, we provide recommendations on how combinations of exosomes/ biomaterials (e.g. hydrogels, stents, cell sheets, cardiac patches, microneedles, spray and 3D tissue matrix) increase the success rate of cell-free therapies which will boost cardiac repair and regeneration in the clinical settings of CVDs.</p></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"1 ","pages":"Article 100010"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773041722000051/pdfft?md5=83d800a9d9334377c88c5c73fb555965&pid=1-s2.0-S2773041722000051-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48288316","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}
Hyun-Ji Park , John M. Kelly , Jessica R. Hoffman , Felipe Takaesu , William Schwartzman , Anudari Ulziibayar , Takahiro Kitsuka , Eric Heuer , Asigul Yimit , Raphael Malbrue , Cole Anderson , Adrienne Morrison , Aymen Naguib , Christopher Mckee , Andrew Harrison , Brian Boe , Aimee Armstrong , Arash Salavitabar , Andrew Yates , Toshiharu Shinoka , Michael E. Davis
{"title":"Computational analysis of serum-derived extracellular vesicle miRNAs in juvenile sheep model of single stage Fontan procedure","authors":"Hyun-Ji Park , John M. Kelly , Jessica R. Hoffman , Felipe Takaesu , William Schwartzman , Anudari Ulziibayar , Takahiro Kitsuka , Eric Heuer , Asigul Yimit , Raphael Malbrue , Cole Anderson , Adrienne Morrison , Aymen Naguib , Christopher Mckee , Andrew Harrison , Brian Boe , Aimee Armstrong , Arash Salavitabar , Andrew Yates , Toshiharu Shinoka , Michael E. Davis","doi":"10.1016/j.vesic.2022.100013","DOIUrl":"10.1016/j.vesic.2022.100013","url":null,"abstract":"<div><p>Patients with single ventricle heart defects requires a series of staged open-heart procedures, termed Fontan palliation. However, while lifesaving, these operations are associated with significant morbidity and early mortality. The attendant complications are thought to arise in response to the abnormal hemodynamics induced by Fontan palliation, although the pathophysiology underlying these physicochemical changes in cardiovascular and other organs remain unknown. Here, we investigated the microRNA (miRNA) content in serum and serum-derived extracellular vesicles (EVs) by sequencing small RNAs from a physiologically relevant sheep model of the Fontan operation. The differential expression analysis identified the enriched miRNA clusters in (1) serum vs. serum-derived EVs and (2) pre-Fontan EVs vs. post-Fontan EVs. Metascape analysis showed that the overexpressed subset of EV miRNAs by Fontan procedure target liver-specific cells, underscoring a potentially important pathway involved in the liver dysfunction that occurs as a consequence of Fontan palliation. We also found that post-Fontan EV miRNAs were associated with senescence and cell death, whereas pre-Fontan EV miRNAs were associated with stem cell maintenance and epithelial-to-mesenchymal transition. This study shows great potential to identify novel circulating EV biomarkers from Fontan sheep serum that may be used for the diagnosis, prognosis, and therapeutics for patients that have undergone Fontan palliation.</p></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"1 ","pages":"Article 100013"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9623551/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10757510","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}
Shuhong Wang , Yusheng Lin , Yishi Zhang , Xiaofu Qiu , Yunlong Pan , Sai-Ching Jim Yeung , Hao Zhang
{"title":"Complex RNA world in small extracellular vesicles for liquid biopsy in cancer management","authors":"Shuhong Wang , Yusheng Lin , Yishi Zhang , Xiaofu Qiu , Yunlong Pan , Sai-Ching Jim Yeung , Hao Zhang","doi":"10.1016/j.vesic.2022.100015","DOIUrl":"10.1016/j.vesic.2022.100015","url":null,"abstract":"<div><p>Liquid biopsy is a valuable tool in oncology with its advantages of non-invasiveness, longitudinal sampling, and capturing the intra- and inter-tumor heterogeneity. Small extracellular vesicles (sEVs) are released by cells into various biological fluids, providing a window to ascertain the cellular status of the source cells. Although many aspects of sEV biology are still enigmatic, analysis of sEV contents in biofluids offers readouts with broad applications, and may be superior or complementary to other assays of liquid biopsy. sEVs carry cell-derived biomaterials, including nucleic acids, proteins, lipids, and metabolites. RNAs are dominant components packed in sEVs, consisting of various biotypes. Protected by the phospholipid bilayer outer membrane of the sEVs, sEV RNAs are remarkably stable. Therefore, the RNA cargos originated from the cancer cells might have high potential as biomarkers in analysis of oncological features. This review will (1) characterize the RNA species loaded into sEVs as well as the related RNA metabolism; (2) summarize the molecular mechanisms of RNA sorting into sEVs, and (3) discuss the potential of using liquid biopsy of sEV RNAs in oncology for early diagnosis of tumor, assessment of tumor burden, response to therapy and monitoring minimal residual disease for recurrence and disease progression.</p></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"1 ","pages":"Article 100015"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773041722000105/pdfft?md5=c7e3c8140ad3c669eaf9324e681432da&pid=1-s2.0-S2773041722000105-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43268004","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}
Junjie Zhao , Lizhou Xu , Dongjie Yang , Huijing Tang , Yalin Chen , Xunzhi Zhang , Yunsheng Xu , Rongying Ou , Danyang Li
{"title":"Exosome-driven liquid biopsy for breast cancer: Recent advances in isolation, biomarker identification and detection","authors":"Junjie Zhao , Lizhou Xu , Dongjie Yang , Huijing Tang , Yalin Chen , Xunzhi Zhang , Yunsheng Xu , Rongying Ou , Danyang Li","doi":"10.1016/j.vesic.2022.100006","DOIUrl":"10.1016/j.vesic.2022.100006","url":null,"abstract":"<div><p>Liquid biopsy with minimally invasive emerges as a powerful tool for early screening of breast cancer (BrCa). BrCa derived exosomes which enrich with biological information from their parent cells play essential roles in the evolution and metastasis of BrCa, providing a real-time snapshot of the tumor. This review summaries the recent advances of exosomes studies in liquid biopsy, particularly for BrCa. A number of isolation methods for exosomes are compared in detail. Different exosome biomarkers for detection of BrCa are discussed. Novel approaches for the detection of exosomes towards clinical diagnosis of BrCa are highlighted at the end. We believe the innovations in exosome research will lead to new breakthroughs in the early screening and diagnosis of BrCa.</p></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"1 ","pages":"Article 100006"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773041722000038/pdfft?md5=b8150bb8e21c30c2033d586432751cc3&pid=1-s2.0-S2773041722000038-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"55274768","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}
Xinyue Dai , Zhaoshuo Wang , Miao Fan , Huifang Liu , Xinjian Yang , Xueyi Wang , Xiaohan Zhou , Yunlu Dai , Jinchao Zhang , Zhenhua Li
{"title":"PD-L1 antibodies-armed exosomal vaccine for enhanced cancer immunotherapy by simultaneously in situ activating T cells and blocking PD-1/PD-L1 axis","authors":"Xinyue Dai , Zhaoshuo Wang , Miao Fan , Huifang Liu , Xinjian Yang , Xueyi Wang , Xiaohan Zhou , Yunlu Dai , Jinchao Zhang , Zhenhua Li","doi":"10.1016/j.vesic.2022.100012","DOIUrl":"10.1016/j.vesic.2022.100012","url":null,"abstract":"<div><p>Tumor immunotherapy significantly rewards antigen-specific T-cell responses, which have been recognized as the foundation of adaptive immune responses. However, due to the immunosuppressive effects of the tumor microenvironment, it is still hard to activate T cells in situ. Especially, antigen-specific T cell activity is further limited as tumor cells can evade T cell attack via PD-1/PD-L1 axis. During this work, we used a dendritic cells (DCs)-derivate exosome vaccine to build an immunotherapeutic system that can simultaneously mediate antigenic T cell activity by carrying T cells activating CD80 and MHC to induce humoral immunity. More importantly, in order to interrupt tumor immune escape, we also engineered anti-PD-L1 antibodies (aPD-L1) to block PD-1/PD-L1 axis at the same time. Our antigens-feeding DCs-exosomes with aPD-L1 engineering represents a promising strategy for enhanced cancer immunotherapy by robust activating T cells. The outcomes demonstrated that Exo-OVA-aPD-L1 was successful in inhibiting the growth, recurrence, and metastasis of melanoma.</p></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"1 ","pages":"Article 100012"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773041722000075/pdfft?md5=f8857c50cc77e4b859d5feff22fff131&pid=1-s2.0-S2773041722000075-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41261453","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}
Rongrong Li , Chen Wang , Manqian Zhou , Yue Liu , Shang Chen , Zihan Chai , Haoyan Huang , Kaiyue Zhang , Zhibo Han , Guoqiang Hua , Nadia Benkirane-Jessel , Zhong-Chao Han , Zongjin Li
{"title":"Heparan sulfate proteoglycan-mediated internalization of extracellular vesicles ameliorates liver fibrosis by targeting hepatic stellate cells","authors":"Rongrong Li , Chen Wang , Manqian Zhou , Yue Liu , Shang Chen , Zihan Chai , Haoyan Huang , Kaiyue Zhang , Zhibo Han , Guoqiang Hua , Nadia Benkirane-Jessel , Zhong-Chao Han , Zongjin Li","doi":"10.1016/j.vesic.2022.100018","DOIUrl":"10.1016/j.vesic.2022.100018","url":null,"abstract":"<div><p>Accumulating evidence shows that stem cell-derived extracellular vesicles (EVs) have shown great promise for tissue regeneration and are considered an alternative to cell-based therapy. However, the mechanisms by which EVs induce tissue repair have not been well demonstrated. Previous work indicates that activation of hepatic stellate cells (HSCs) may contribute to the progression of liver fibrosis. Here, we investigate the therapeutic potential of EVs derived from human placental mesenchymal stem cells (hP-MSCs) for the treatment of carbon tetrachloride (CCl4)-induced liver injury. Our data revealed that EVs derived from hP-MSCs effectively ameliorate liver injury by attenuating inflammation and fibrosis. Further data revealed that heparan sulfate proteoglycans (HSPGs) on the surface of HSCs mediate the internalization of EVs. Furthermore, EVs could inhibit the epithelial–mesenchymal transition (EMT) process in HSCs through the downregulated TGF-<span><math><mi>β</mi></math></span>/Smad pathway, which was mediated by miR-744-5p in EVs. Meanwhile, glycosaminoglycans on the surface of EVs play a crucial anti-inflammatory role. In conclusion, our results provide evidence that hP-MSC-derived EVs promote the recovery of liver injury by targeting HSPGs on HSCs and inhibiting liver inflammation through glycosaminoglycans from EVs. These findings may provide a novel theoretical basis for the treatment of liver fibrosis based on EVs.</p></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"1 ","pages":"Article 100018"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773041722000130/pdfft?md5=d75954f4d1b9af37bd48505b0a9c2691&pid=1-s2.0-S2773041722000130-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46753630","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":"Therapeutic and diagnostic potential of extracellular vesicles in amyotrophic lateral sclerosis","authors":"Taylor J. Ellison, S. 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":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"55274786","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}