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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 -
Nature Reviews. Molecular Cell Biology Apr 2018Extracellular vesicles are a heterogeneous group of cell-derived membranous structures comprising exosomes and microvesicles, which originate from the endosomal system... (Review)
Review
Extracellular vesicles are a heterogeneous group of cell-derived membranous structures comprising exosomes and microvesicles, which originate from the endosomal system or which are shed from the plasma membrane, respectively. They are present in biological fluids and are involved in multiple physiological and pathological processes. Extracellular vesicles are now considered as an additional mechanism for intercellular communication, allowing cells to exchange proteins, lipids and genetic material. Knowledge of the cellular processes that govern extracellular vesicle biology is essential to shed light on the physiological and pathological functions of these vesicles as well as on clinical applications involving their use and/or analysis. However, in this expanding field, much remains unknown regarding the origin, biogenesis, secretion, targeting and fate of these vesicles.
Topics: Animals; Biological Transport, Active; Cell-Derived Microparticles; Exosomes; Extracellular Vesicles; Humans; Membrane Fusion; Models, Biological; Organelle Biogenesis; Signal Transduction
PubMed: 29339798
DOI: 10.1038/nrm.2017.125 -
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 -
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 -
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 -
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 -
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 -
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 -
Methods in Molecular Biology (Clifton,... 2017Extracellular vesicles (EVs) are released by mammalian cells and are thought to be important mediators of intercellular communication. There are many methods for...
Extracellular vesicles (EVs) are released by mammalian cells and are thought to be important mediators of intercellular communication. There are many methods for isolating EVs from cell culture media, but the most popular methods involve purification based on ultracentrifugation . Here, we provide a detailed protocol for isolating EVs by differential ultracentrifugation and analyzing EV proteins (such as the tetraspanins CD9 , CD63 and CD81 ) by western blotting.
Topics: Animals; Blotting, Western; Cell Fractionation; Extracellular Vesicles; Humans
PubMed: 28828654
DOI: 10.1007/978-1-4939-7253-1_12 -
Stem Cell Research & Therapy Mar 2018Mesenchymal stem cells (MSCs) are multipotent stem cells that have gained significant attention in the field of regenerative medicine. The differentiation potential... (Review)
Review
Mesenchymal stem cells (MSCs) are multipotent stem cells that have gained significant attention in the field of regenerative medicine. The differentiation potential along with paracrine properties of MSCs have made them a key option for tissue repair. The paracrine functions of MSCs are applied through secreting soluble factors and releasing extracellular vesicles like exosomes and microvesicles. Extracellular vesicles are predominantly endosomal in origin and contain a cargo of miRNA, mRNA, and proteins that are transferred from their original cells to target cells. Recently it has emerged that extracellular vesicles alone are responsible for the therapeutic effect of MSCs in plenty of animal diseases models. Hence, MSC-derived extracellular vesicles may be used as an alternative MSC-based therapy in regenerative medicine. In this review we discuss MSC-derived extracellular vesicles and their therapeutic potential in various diseases.
Topics: Animals; Extracellular Vesicles; Humans; Mesenchymal Stem Cells; Paracrine Communication; Regenerative Medicine
PubMed: 29523213
DOI: 10.1186/s13287-018-0791-7