{"title":"Leveraging biomimetic synthesis strategy for next-generation dendritic cell nanovaccines","authors":"Yutian Xia, Jianzhong Zhang","doi":"10.20517/evcna.2022.35","DOIUrl":"https://doi.org/10.20517/evcna.2022.35","url":null,"abstract":"The activation of CD8+ cytotoxic T-lymphocytes (CTLs) plays the central role in cancer immunotherapy, which depends on the efficient recognition of peptide-major histocompatibility complex (pMHC) by the T cell receptor (TCR) for the first signal, and B7-CD28 co-stimulating for the second signal. To achieve the potent immune stimulatory effect, a genetically engineered cellular membrane nanovesicles platform that integrates antigen self-presentation and immunosuppression reversal (ASPIRE) for cancer immunotherapy was designed. In preclinical mouse models, ASPIRE could markedly improve antigen delivery to lymphoid organs and generate broad-spectrum T-cell responses that eliminate established tumors. This review highlights that the ASPIRE system represents a novel strategy for personalized cancer immunotherapy.","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84871000","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}
A. Chen, Heng-Song Tian, Nana Yang, Zhi-jun Zhang, Guo-Yuan Yang, W. Cui, Yaohui Tang
{"title":"Towards extracellular vesicle delivery systems for tissue regeneration: material design at the molecular level","authors":"A. Chen, Heng-Song Tian, Nana Yang, Zhi-jun Zhang, Guo-Yuan Yang, W. Cui, Yaohui Tang","doi":"10.20517/evcna.2022.37","DOIUrl":"https://doi.org/10.20517/evcna.2022.37","url":null,"abstract":"The discovery and development of extracellular vesicles in tissue engineering have shown great potential for tissue regenerative therapies. However, their vesicle nature requires dosage-dependent administration and efficient interactions with recipient cells. Researchers have resorted to biomaterials for localized and sustained delivery of extracellular vesicles to the targeted cells, but not much emphasis has been paid on the design of the materials, which deeply impacts their molecular interactions with the loaded extracellular vesicles and subsequent delivery. Therefore, we present in this review a comprehensive survey of extracellular vesicle delivery systems from the viewpoint of material design at the molecular level. We start with general requirements of the materials and delve into different properties of delivery systems as a result of different designs, from material selections to processing strategies. Based on these differences, we analyzed the performance of extracellular vesicle delivery and tissue regeneration in representative studies. In light of the current missing links within the relationship of material structures, physicochemical properties and delivery performances, we provide perspectives on the interactions of materials and extracellular vesicles and the possible extension of materials. This review aims to be a strategic enlightenment for the future design of extracellular vesicle delivery systems to facilitate their translation from basic science to clinical applications.","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81245111","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}
Vaughn D Craddock, Christine M Cook, Navneet K Dhillon
{"title":"Exploring extracellular vesicles as mediators of clinical disease and vehicles for viral therapeutics: Insights from the COVID-19 pandemic.","authors":"Vaughn D Craddock, Christine M Cook, Navneet K Dhillon","doi":"10.20517/evcna.2022.19","DOIUrl":"https://doi.org/10.20517/evcna.2022.19","url":null,"abstract":"<p><p>The COVID-19 pandemic has challenged researchers to rapidly understand the capabilities of the SARS-CoV-2 virus and investigate potential therapeutics for SARS-CoV-2 infection. COVID-19 has been associated with devastating lung and cardiac injury, profound inflammation, and a heightened coagulopathic state, which may, in part, be driven by cellular crosstalk facilitated by extracellular vesicles (EVs). In recent years, EVs have emerged as important biomarkers of disease, and while extracellular vesicles may contribute to the spread of COVID-19 infection from one cell to the next, they also may be engineered to play a protective or therapeutic role as decoys or \"delivery drivers\" for therapeutic agents. This review explores these roles and areas for future study.</p>","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9348627/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40583726","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 reproduction and pregnancy","authors":"Tahlia I. Smith, A. Russell","doi":"10.20517/evcna.2022.27","DOIUrl":"https://doi.org/10.20517/evcna.2022.27","url":null,"abstract":"Extracellular vesicles (EVs) are small, lipid-bound packages that are secreted by all cell types and have been implicated in many diseases, such as cancer and neurodegenerative disorders. Though limited, an exciting new area of EV research focuses on their role in the reproductive system and pregnancy. In males, EVs have been implicated in sperm production and maturation. In females, EVs play a vital role in maintaining reproductive organ homeostasis and pregnancy, including the regulation of folliculogenesis, ovulation, and embryo implantation. During the development and maintenance of a pregnancy, the placenta is the main form of communication between the mother and the developing fetus. To support the developing fetus, the placenta will act as numerous vital organs until birth, and release EVs into the maternal and fetal bloodstream. EVs play an important role in cell-to-cell communication and may mediate the pathophysiology of pregnancy-related disorders such as preeclampsia, gestational diabetes mellitus, preterm birth, and intrauterine growth restriction, and potentially serve as noninvasive biomarkers for these conditions. In addition, EVs may also mediate processes involved in both male and female infertility. Together, the EVs secreted by both the male and female reproductive tracts work to promote reproductive fertility and play vital roles in mediating maternal-fetal crosstalk and pregnancy maintenance.","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89789591","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}
Charlotte V Hegeman, Olivier G. de Jong, M. Lorenowicz
{"title":"A kaleidoscopic view of extracellular vesicles in lysosomal storage disorders","authors":"Charlotte V Hegeman, Olivier G. de Jong, M. Lorenowicz","doi":"10.20517/evcna.2022.41","DOIUrl":"https://doi.org/10.20517/evcna.2022.41","url":null,"abstract":"Extracellular vesicles (EVs) are a heterogeneous population of stable lipid membrane particles that play a critical role in the regulation of numerous physiological and pathological processes. EV cargo, which includes lipids, proteins, and RNAs including miRNAs, is affected by the metabolic status of the parental cell. Concordantly, abnormalities in the autophagic-endolysosomal pathway, as seen in lysosomal storage disorders (LSDs), can affect EV release as well as EV cargo. LSDs are a group of over 70 inheritable diseases, characterized by lysosomal dysfunction and gradual accumulation of undigested molecules. LSDs are caused by single gene mutations that lead to a deficiency of a lysosomal protein or lipid. Lysosomal dysfunction sets off a cascade of alterations in the endolysosomal pathway that can affect autophagy and alter calcium homeostasis, leading to energy imbalance, oxidative stress, and apoptosis. The pathophysiology of these diseases is very heterogenous, complex, and currently incompletely understood. LSDs lead to progressive multisystemic symptoms that often include neurological deficits. In this review, a kaleidoscopic overview will be given on the roles of EVs in LSDs, from their contribution to pathology and diagnostics to their role as drug delivery vehicles. Furthermore, EV cargo and surface engineering strategies will be discussed to show the potential of EVs in future LSD treatment, both in the context of enzyme replacement therapy, as well as future gene editing strategies like CRISPR/Cas. The use of engineered EVs as drug delivery vehicles may mask therapeutic cargo from the immune system and protect it from degradation, improving circulation time and targeted delivery.","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75121118","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":"Liquid biopsy of extracellular vesicle biomarkers for prostate cancer personalized treatment decision","authors":"Meng Han, Bairen Pang, Cheng Zhou, Xin Li, Qi Wang, Junhui Jiang, Yong Li","doi":"10.20517/evcna.2021.20","DOIUrl":"https://doi.org/10.20517/evcna.2021.20","url":null,"abstract":"Liquid biopsy of tumor-derived extracellular vesicles (EVs) has great potential as a biomarker source for prostate cancer (CaP) early diagnosis and predicting the stages of cancer. The contents of EVs play an important role in intercellular communication and have specific expression in blood and urine samples from CaP patients. Powered by high-throughput, next-generation sequencing and proteomic technologies, novel EV biomarkers are easily detected in a non-invasive manner in different stages of CaP patients. These identified potential biomarkers can be further validated with a large sample size, machine learning model, and other different methods to improve the sensitivity and specificity of CaP diagnosis. The EV-based liquid biopsy is a novel and less-invasive alternative to surgical biopsies which would enable clinicians to potentially discover a whole picture of tumor through a simple blood or urine sample. In summary, this approach holds promise for developing personalized medicine to guide treatment decisions precisely for CaP patients.","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85799590","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":"Acknowledgement to reviewers of Extracellular Vesicles and Circulating Nucleic Acids in 2021","authors":"","doi":"10.20517/evcna.2022.01","DOIUrl":"https://doi.org/10.20517/evcna.2022.01","url":null,"abstract":"","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88545228","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":"Liquid biopsy for monitoring medulloblastoma","authors":"R. Eibl, M. Schneemann","doi":"10.20517/evcna.2022.36","DOIUrl":"https://doi.org/10.20517/evcna.2022.36","url":null,"abstract":"Despite recent progress in molecular diagnostics defining four distinct medulloblastoma groups, the clinical management of these malignant childhood tumors of the cerebellum remains challenging. After surgical removal of the tumor, both cytotoxic chemotherapy and irradiation can offer additional curative benefits, but they also include a significant risk of long-term damage. Early molecular profiling aims to predict the outcome of such aggressive therapies. This prevents unnecessary damage to patients who may not need it and helps to identify those patients with remaining tumor cells who may benefit from more aggressive treatment with the intent to cure. Monitoring tumor evolution in real time allows personalized precision medicine with an immediate clinical response resulting in a better outcome. Liquid biopsy includes various methodologies already applied in numerous studies and clinical trials for common cancers including brain tumors, but information on medulloblastomas is limited. This review summarizes the recent developments of how liquid biopsy can support or even replace the standard monitoring of medulloblastomas by medical imaging or cytology and discusses what will be needed to make liquid biopsy a new gold standard in diagnosis, therapy, and follow-up of medulloblastomas for the benefit of the patients.","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75645476","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":"Emerging frontiers of cell-free DNA fragmentomics","authors":"Xi Hu, Spencer C. Ding, P. Jiang","doi":"10.20517/evcna.2022.34","DOIUrl":"https://doi.org/10.20517/evcna.2022.34","url":null,"abstract":"Analysis of cell-free DNA (cfDNA) in the blood has shown promise for monitoring a variety of biological processes. Plasma cfDNA is a mixture comprising DNA molecules released from various bodily tissues, mediated by characteristic DNA fragmentations occurring during cell death. Fragmentation of cfDNA is non-random and contains tissue-of-origin information, which has been demonstrated in circulating fetal, tumoral, and transplanted organ-derived cfDNA molecules. Many studies have elucidated a plurality of fragmentomic markers for noninvasive prenatal, cancer, and organ transplantation assessment, such as fragment sizes, fragment ends, end motifs, and nucleosome footprints. Recently, researchers have further revealed the large population of previously unidentified long cfDNA molecules (kilobases in size) in the plasma DNA pool. This review focuses on the emerging biological properties of cfDNA, together with a discussion on its potential clinical implications.","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72547440","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}
Ying Yang, C. Zeng, Kun Yang, Shaohua Xu, Zhou Zhang, Qinyun Cai, Chuan He, Wei Zhang, Song-Mei Liu
{"title":"Genome-wide Analysis Reflects Novel 5-Hydroxymethylcytosines Implicated in Diabetic Nephropathy and the Biomarker Potential.","authors":"Ying Yang, C. Zeng, Kun Yang, Shaohua Xu, Zhou Zhang, Qinyun Cai, Chuan He, Wei Zhang, Song-Mei Liu","doi":"10.20517/evcna.2022.03","DOIUrl":"https://doi.org/10.20517/evcna.2022.03","url":null,"abstract":"Aim Diabetic nephropathy (DN) has become the most common cause of end-stage renal disease (ESRD) in most countries. Elucidating novel epigenetic contributors to DN can not only enhance our understanding of this complex disorder, but also lay the foundation for developing more effective monitoring tools and preventive interventions in the future, thus contributing to our ultimate goal of improving patient care. Methods The 5hmC-Seal, a highly selective, chemical labeling technique, was used to profile genome-wide 5-hydroxymethylcytosines (5hmC), a stable cytosine modification type marking gene activation, in circulating cell-free DNA (cfDNA) samples from a cohort of patients recruited at Zhongnan Hospital, including T2D patients with nephropathy (DN, n = 12), T2D patients with non-DN vascular complications (non-DN, n = 29), and T2D patients without any complication (controls, n = 14). Differentially analysis was performed to find DN-associated 5hmC features, followed by the exploration of biomarker potential of 5hmC in cfDNA for DN using a machine learning approach. Results Genome-wide analyses of 5hmC in cfDNA detected 427 and 336 differential 5hmC modifications associated with DN, compared with non-DN individuals and controls, and suggested relevant pathways such as NOD-like receptor signaling pathway and tyrosine metabolism. Our exploration using a machine learning approach revealed an exploratory model comprised of ten 5hmC genes showing the possibility to distinguish DN from non-DN individuals or controls. Conclusion Genome-wide analysis suggests the possibility of exploiting novel 5hmC in patient-derived cfDNA as a non-invasive tool for monitoring DN in high risk T2D patients in the future.","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74925619","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}