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Bioscience Reports Jan 2019Apoptosis is widely known as programmed cell death eliciting no inflammatory responses. The intricacy of apoptosis has been a focus of an array of researches,... (Review)
Review
Apoptosis is widely known as programmed cell death eliciting no inflammatory responses. The intricacy of apoptosis has been a focus of an array of researches, accumulating a wealth of knowledge which led to not only a better understanding of the fundamental process, but also potent therapies of diseases. The classic intrinsic and extrinsic signaling pathways of apoptosis, along with regulatory factors have been well delineated. Drugs and therapeutic measures designed based on current understanding of apoptosis have long been employed. Small-molecule apoptosis inducers have been clinically used for eliminating morbid cells and therefore treating diseases, such as cancer. Biologics with improved apoptotic efficacy and selectivity, such as recombinant proteins and antibodies, are being extensively researched and some have been approved by the FDA. Apoptosis also produces membrane-bound vesicles derived from disassembly of apoptotic cells, now known as apoptotic bodies (ApoBDs). These little sealed sacs containing information as well as substances from dying cells were previously regarded as garbage bags until they were discovered to be capable of delivering useful materials to healthy recipient cells (e.g., autoantigens). In this review, current understandings and knowledge of apoptosis were summarized and discussed with a focus on apoptosis-related therapeutic applications and ApoBDs.
Topics: Apoptosis; Caspases; Drug Design; Extracellular Vesicles; Humans; Neoplasms
PubMed: 30530866
DOI: 10.1042/BSR20180992 -
American Journal of Physiology. Cell... Jan 2020Extracellular vesicles (EVs) are small lipid membrane vesicles that are secreted from almost all kinds of cells into the extracellular space. EVs are widely accepted to... (Review)
Review
Extracellular vesicles (EVs) are small lipid membrane vesicles that are secreted from almost all kinds of cells into the extracellular space. EVs are widely accepted to be involved in various cellular processes; in particular, EVs derived from cancer cells have been reported to play important roles in modifying the tumor microenvironment and promoting tumor progression. In addition, EVs derived from cancer cells encapsulate various kinds of tumor-specific molecules, such as proteins and RNAs, which contribute to cancer malignancy. Therefore, the unveiling of the precise mechanism of intercellular communication via EVs in cancer patients will provide a novel strategy for cancer treatment. Furthermore, a focus on the contents of EVs could promote the use of EVs in body fluids as clinically useful diagnostic and prognostic biomarkers. In this review, we summarize the current research knowledge on EVs as biomarkers and therapeutic targets and discuss their potential clinical applications.
Topics: Animals; Antineoplastic Agents; Biomarkers, Tumor; Extracellular Vesicles; Gene Expression Regulation, Neoplastic; Hemofiltration; Humans; Molecular Targeted Therapy; Neoplasms; Predictive Value of Tests; Signal Transduction
PubMed: 31693397
DOI: 10.1152/ajpcell.00280.2019 -
Immunological Reviews Nov 2022Neutrophils are immune cells involved in several inflammatory and homeostatic processes. Their capacity to release cargo can be classified based on whether the cargo is... (Review)
Review
Neutrophils are immune cells involved in several inflammatory and homeostatic processes. Their capacity to release cargo can be classified based on whether the cargo is released on its own, or in conjunction with plasma membrane structures. Examples of plasma membrane-free secretion modes are degranulation, neutrophil extracellular trap (NET) release, and cytokine release through inflammasome formation. The most studied membrane-covered neutrophil-derived structures are exosomes and ectosomes that are collectively called extracellular vesicles (EV). Apoptotic vesicles are another recognized EV subtype. Over the last decade, additional membrane-covered neutrophil-derived structures were characterized: migratory cytoplasts, migrasomes, and elongated neutrophil-derived structures (ENDS). All these structures are smaller than the neutrophils, cannot reproduce themselves, and thus meet the latest consensus definition of EVs. In this review, we focus on the less well-studied neutrophil EVs: apoptotic vesicles, cytoplasts, migrasomes, and ENDS.
Topics: Cell-Derived Microparticles; Cytokines; Extracellular Vesicles; Humans; Inflammasomes; Neutrophils
PubMed: 35665941
DOI: 10.1111/imr.13103 -
Trends in Cell Biology Aug 2023The study of extracellular vesicles (EVs) and nanoparticles (NPs) is rapidly expanding because recent discoveries have revealed a much greater complexity and diversity... (Review)
Review
The study of extracellular vesicles (EVs) and nanoparticles (NPs) is rapidly expanding because recent discoveries have revealed a much greater complexity and diversity than was appreciated only a few years ago. New types of EVs and NPs have recently been described. Proteins and nucleic acids previously thought to be packaged in exosomes appear to be more enriched in different types of EVs and in two recently identified amembranous NPs, exomeres and supermeres. Thus, our understanding of the cell biology and intercellular communication facilitated by the release of EVs and NPs is in a state of flux. In this review, we describe the different types of EVs and NPs, highlight recent advances, and present major outstanding questions.
Topics: Humans; Extracellular Vesicles; Exosomes; Cell Communication; Nucleic Acids
PubMed: 36737375
DOI: 10.1016/j.tcb.2023.01.002 -
Cancer Cell Dec 2016Tumor-secreted extracellular vesicles (EVs) are critical mediators of intercellular communication between tumor cells and stromal cells in local and distant... (Review)
Review
Tumor-secreted extracellular vesicles (EVs) are critical mediators of intercellular communication between tumor cells and stromal cells in local and distant microenvironments. Accordingly, EVs play an essential role in both primary tumor growth and metastatic evolution. EVs orchestrate multiple systemic pathophysiological processes, such as coagulation, vascular leakiness, and reprogramming of stromal recipient cells to support pre-metastatic niche formation and subsequent metastasis. Clinically, EVs may be biomarkers and novel therapeutic targets for cancer progression, particularly for predicting and preventing future metastatic development.
Topics: Biomarkers, Tumor; Cell Communication; Exosomes; Extracellular Vesicles; Humans; Neoplasm Metastasis; Neoplasms; Prognosis; Tumor Microenvironment
PubMed: 27960084
DOI: 10.1016/j.ccell.2016.10.009 -
Frontiers in Immunology 2020Diabetic nephropathy (DN) is a major microvascular complication of diabetes mellitus. It is the most frequent cause of end-stage renal disease with no definitive therapy... (Review)
Review
Diabetic nephropathy (DN) is a major microvascular complication of diabetes mellitus. It is the most frequent cause of end-stage renal disease with no definitive therapy available so far. Extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies, are nano- and micron-sized heterogeneous vesicles that can be secreted by almost all cell types. Importantly, EVs contain many biologically active materials, such as RNAs, DNAs, proteins, and lipids, from their parental cells, which can be transported to their recipient cells to mediate intercellular communication and signaling. Accumulating studies demonstrated that EVs, mainly exosomes and microvesicles, participated in the pathophysiological process of DN. Recently emerging studies also found that the contents of EVs in the urine (miRNAs, mRNAs, and proteins) could be used as potential biomarkers for DN. Therefore, in this mini-review, the generation, isolation methods, and biological function of EVs were introduced, and then the current information about the mechanism and the diagnostic value in the development of DN was summarized. Moreover, the review also discussed the future challenges of exploring the role of EVs in kidney disease.
Topics: Animals; Biomarkers; Cell Communication; Diabetic Nephropathies; Extracellular Vesicles; Humans; Kidney; Signal Transduction
PubMed: 32582146
DOI: 10.3389/fimmu.2020.00943 -
Advanced Drug Delivery Reviews Nov 2021Extracellular vesicles (EVs) are natural nanoparticles containing biologically active molecules. They are important mediators of intercellular communication and can be... (Review)
Review
Extracellular vesicles (EVs) are natural nanoparticles containing biologically active molecules. They are important mediators of intercellular communication and can be exploited therapeutically by various bioengineering approaches. To accurately determine the therapeutic potential of EVs in pre-clinical and clinical settings, dependable dosing strategies are of utmost importance. However, the field suffers from inconsistencies comprising all areas of EV production and characterisation. Therefore, a standardised and well-defined process in EV quantification, key to reliable therapeutic EV dosing, remains to be established. Here, we examined 64 pre-clinical studies for EV-based therapeutics with respect to their applied EV dosing strategies. We identified variations in effective dosing strategies irrespective of the applied EV purification method and cell source. Moreover, we found dose discrepancies depending on the disease model, where EV doses were selected without accounting for published EV pharmacokinetics or biodistribution patterns. We therefore propose to focus on qualitative aspects when dosing EV-based therapeutics, such as the potency of the therapeutic cargo entity. This will ensure batch-to-batch reliability and enhance reproducibility between applications. Furthermore, it will allow for the successful benchmarking of EV-based therapeutics compared to other nanoparticle drug delivery systems, such as viral vector-based or lipid-based nanoparticle approaches.
Topics: Drug Delivery Systems; Extracellular Vesicles; Humans; Lipids; Nanoparticles
PubMed: 34481030
DOI: 10.1016/j.addr.2021.113961 -
Nature Immunology May 2021Extracellular vesicles have emerged as prominent regulators of the immune response during tumor progression. EVs contain a diverse repertoire of molecular cargo that... (Review)
Review
Extracellular vesicles have emerged as prominent regulators of the immune response during tumor progression. EVs contain a diverse repertoire of molecular cargo that plays a critical role in immunomodulation. Here, we identify the role of EVs as mediators of communication between cancer and immune cells. This expanded role of EVs may shed light on the mechanisms behind tumor progression and provide translational diagnostic and prognostic tools for immunologists.
Topics: Animals; Disease Progression; Extracellular Vesicles; Humans; Immunotherapy; Neoplasms; Signal Transduction; Tumor Escape; Tumor Microenvironment
PubMed: 33753940
DOI: 10.1038/s41590-021-00899-0 -
Advanced Drug Delivery Reviews 2020Over the past decades, a multitude of synthetic drug delivery systems has been developed and introduced to the market. However, applications of such systems are limited... (Review)
Review
Over the past decades, a multitude of synthetic drug delivery systems has been developed and introduced to the market. However, applications of such systems are limited due to inefficiency, cytotoxicity and/or immunogenicity. At the same time, the field of natural drug carrier systems has grown rapidly. One of the most prominent examples of such natural carriers are extracellular vesicles (EVs). EVs are cell-derived membranous particles which play important roles in intercellular communication. EVs possess a number of characteristics that qualify them as promising vehicles for drug delivery. In order to take advantage of these attributes, an in-depth understanding of why EVs are such unique carrier systems and how we can exploit their qualities is pivotal. Here, we review unique EV features that are relevant for drug delivery and highlight emerging strategies to make use of those features for drug loading and targeted delivery.
Topics: Animals; Drug Delivery Systems; Extracellular Vesicles; Humans
PubMed: 32305351
DOI: 10.1016/j.addr.2020.04.004 -
The Journal of Neuroscience : the... Nov 2019Extracellular vesicles (EVs) include exosomes and microvesicles and have been shown to have roles in the CNS ranging from the removal of unwanted biomolecules to... (Review)
Review
Extracellular vesicles (EVs) include exosomes and microvesicles and have been shown to have roles in the CNS ranging from the removal of unwanted biomolecules to intercellular communication to the spread of pathogenic proteins associated with neurodegenerative diseases. EVs carry protein, lipid, and genetic cargo, and research over more than a decade has shown that they contain the misfolded forms of proteins associated with Alzheimer's, Parkinson's, and the prion diseases. Altered genetic cargo, usually in the form of miRNAs, have also been identified in EVs patients with these diseases, suggesting that EVs may be a source of disease biomarkers. Whether EVs play a key role in the pathogenesis of neurological diseases remains to be firmly established because most current research is performed using cell culture and transgenic animal models. If EVs are identified as a key pathological contributor to neurological conditions, they will form a novel target for therapeutic intervention. This Dual Perspectives article will discuss the current understanding of the role of EVs in neurological diseases and raise some of the limitations of our current understandings of this field.
Topics: Animals; Brain; Cell Communication; Exosomes; Extracellular Vesicles; Humans; Neurodegenerative Diseases
PubMed: 31748282
DOI: 10.1523/JNEUROSCI.0147-18.2019