scholarly journals Extracellular Vesicles in Modifying the Effects of Ionizing Radiation

2019 ◽  
Vol 20 (22) ◽  
pp. 5527 ◽  
Author(s):  
Tünde Szatmári ◽  
Rita Hargitai ◽  
Géza Sáfrány ◽  
Katalin Lumniczky
Keyword(s):  
Ionizing Radiation ◽  
Extracellular Vesicles ◽  
Radiation Effects ◽  
Cell Types ◽  
Tumor Formation ◽  
The Body ◽  
Target Cells ◽  
Cell Of Origin ◽  
Radiation Induced ◽  
Almost All

Extracellular vesicles (EVs) are membrane-coated nanovesicles actively secreted by almost all cell types. EVs can travel long distances within the body, being finally taken up by the target cells, transferring information from one cell to another, thus influencing their behavior. The cargo of EVs comprises of nucleic acids, lipids, and proteins derived from the cell of origin, thereby it is cell-type specific; moreover, it differs between diseased and normal cells. Several studies have shown that EVs have a role in tumor formation and prognosis. It was also demonstrated that ionizing radiation can alter the cargo of EVs. EVs, in turn can modulate radiation responses and they play a role in radiation-induced bystander effects. Due to their biocompatibility and selective targeting, EVs are suitable nanocarrier candidates of drugs in various diseases, including cancer. Furthermore, the cargo of EVs can be engineered, and in this way they can be designed to carry certain genes or even drugs, similar to synthetic nanoparticles. In this review, we describe the biological characteristics of EVs, focusing on the recent efforts to use EVs as nanocarriers in oncology, the effects of EVs in radiation therapy, highlighting the possibilities to use EVs as nanocarriers to modulate radiation effects in clinical applications.

scholarly journals Microbial extracellular RNAs and their roles in human diseases

2020 ◽  
Vol 245 (10) ◽  
pp. 845-850 ◽  
Author(s):  
Heon-Jin Lee
Keyword(s):  
Extracellular Vesicles ◽  
Cell Types ◽  
Human Cells ◽  
The Body ◽  
Human Diseases ◽  
Host Responses ◽  
Target Cells ◽  
Extracellular Rna ◽  
Communication Signals ◽  
Novel Therapeutic Strategies

Extracellular RNAs (exRNAs) are released by extracellular vesicles, small membranous nanoparticles secreted by all cell types. When transported into cells, exRNAs can modulate gene expression or cellular responses in the target cells since many small RNAs have regulatory functions. Indeed, it is widely acknowledged that endogenous exRNAs in the human body are related to various diseases. However, microbial exRNAs have been less studied, and their connection to host diseases has just begun to be explored. In this review, I will discuss analytical methods for exRNAs and the potential use of exRNAs as disease biomarkers. I also consider current progress in understanding the regulation of host mechanisms by microbial exRNAs as inter-kingdom communication, efforts to utilize extracellular vesicles as therapeutic vehicles loaded with engineered RNA cargos, and a putative connection between microbial exRNA-based regulation of host responses and human diseases such as Alzheimer’s. This overview aims to present novel insights into pathogenesis with regard to the function of microbial exRNAs as “disease-relevant travelers.” Impact statement The number of commensal bacteria in the body surpasses the number of actual human cells. Thus, various interactions between microbes and human cells constitute an inevitable phenomenon. Recent evidence has led to bacterial extracellular RNAs (exRNAs) being proposed as good candidates for microbe–host inter-kingdom communication tools as they can modulate the expression of host genes. However, research findings on the relevance of interactions between extracellular RNA and human diseases are still in their infancy. Nevertheless, substantial data suggest that microbial exRNAs are implicated in various human diseases both at local and distant sites. By exploring various scenarios for the involvement of microbial exRNAs in human diseases, we may better understand the role of exRNAs as “communication signals” for diseases and thereby develop novel therapeutic strategies by using them and their carrier extracellular vesicles.

scholarly journals Role of Extracellular Vesicles in Hematological Malignancies

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Stefania Raimondo ◽  
Chiara Corrado ◽  
Lavinia Raimondi ◽  
Giacomo De Leo ◽  
Riccardo Alessandro
Keyword(s):  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Hematological Malignancies ◽  
Predictive Biomarkers ◽  
Cell Types ◽  
Target Cells ◽  
Specific Cell ◽  
Cell Of Origin ◽  
Cell Functions

In recent years the role of tumor microenvironment in the progression of hematological malignancies has been widely recognized. Recent studies have focused on how cancer cells communicate within the microenvironment. Among several factors (cytokines, growth factors, and ECM molecules), a key role has been attributed to extracellular vesicles (EV), released from different cell types. EV (microvesicles and exosomes) may affect stroma remodeling, host cell functions, and tumor angiogenesis by inducing gene expression modulation in target cells, thus promoting cancer progression and metastasis. Microvesicles and exosomes can be recovered from the blood and other body fluids of cancer patients and contain and deliver genetic and proteomic contents that reflect the cell of origin, thus constituting a source of new predictive biomarkers involved in cancer development and serving as possible targets for therapies. Moreover, due to their specific cell-tropism and bioavailability, EV can be considered natural vehicles suitable for drug delivery. Here we will discuss the recent advances in the field of EV as actors in hematological cancer progression, pointing out the role of these vesicles in the tumor-host interplay and in their use as biomarkers for hematological malignancies.

scholarly journals Current methods for the isolation of extracellular vesicles

2013 ◽  
Vol 394 (10) ◽  
pp. 1253-1262 ◽  
Author(s):  
Fatemeh Momen-Heravi ◽  
Leonora Balaj ◽  
Sara Alian ◽  
Pierre-Yves Mantel ◽  
Allison E. Halleck ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Molecular Mechanisms ◽  
Magnetic Beads ◽  
Cell Types ◽  
Target Cells ◽  
Cell Of Origin ◽  
Novel Technologies ◽  
Advantages And Disadvantages ◽  
Isolation Methods ◽  
Technical Advances

Abstract Extracellular vesicles (EVs), including microvesicles and exosomes, are nano- to micron-sized vesicles, which may deliver bioactive cargos that include lipids, growth factors and their receptors, proteases, signaling molecules, as well as mRNA and non-coding RNA, released from the cell of origin, to target cells. EVs are released by all cell types and likely induced by mechanisms involved in oncogenic transformation, environmental stimulation, cellular activation, oxidative stress, or death. Ongoing studies investigate the molecular mechanisms and mediators of EVs-based intercellular communication at physiological and oncogenic conditions with the hope of using this information as a possible source for explaining physiological processes in addition to using them as therapeutic targets and disease biomarkers in a variety of diseases. A major limitation in this evolving discipline is the hardship and the lack of standardization for already challenging techniques to isolate EVs. Technical advances have been accomplished in the field of isolation with improving knowledge and emerging novel technologies, including ultracentrifugation, microfluidics, magnetic beads and filtration-based isolation methods. In this review, we will discuss the latest advances in methods of isolation methods and production of clinical grade EVs as well as their advantages and disadvantages, and the justification for their support and the challenges that they encounter.

scholarly journals Emerging roles of extracellular vesicles in physiology and disease

2020 ◽  
Author(s):  
Rikinari Hanayama
Keyword(s):  
Communication Networks ◽  
Extracellular Vesicles ◽  
Culture Media ◽  
Membrane Vesicles ◽  
Cell Types ◽  
Target Cells ◽  
Cell Culture Media ◽  
Research Fields ◽  
Research Findings ◽  
Almost All

Abstract Extracellular vesicles (EVs), such as exosomes and microvesicles, are small membrane vesicles secreted by almost all cell types and are abundant in blood, body fluids, such as urine, spinal fluid, tears and saliva, and cell culture media. From an evolutionary perspective, they are biologically significant as a means for expelling unwanted cellular contents. Recently, EVs have received considerable attention as messengers of intercellular communication networks, allowing the exchange of proteins and lipids between the cells producing them and target cells that trigger various cellular responses. EVs also carry mRNAs and microRNAs inside them, transferring genetic information among cells. In addition, the expression pattern of these molecules is related to the cellular state and the progression of diseases, and the search for biomarkers within the EV is underway in many research fields. However, the physiological and pathophysiological roles of EVs remain largely elusive. Therefore, in this special issue, we have compiled reviews of the latest research findings on EV research.

scholarly journals Urinary Extracellular Vesicles: Uncovering the Basis of the Pathological Processes in Kidney-Related Diseases

2021 ◽  
Vol 22 (12) ◽  
pp. 6507
Author(s):  
Giulia Cricrì ◽  
Linda Bellucci ◽  
Giovanni Montini ◽  
Federica Collino
Keyword(s):  
Extracellular Vesicles ◽  
Cell Types ◽  
Diagnostic Techniques ◽  
Cell Contact ◽  
Glomerular Filtration Barrier ◽  
Alternative Source ◽  
Filtration Barrier ◽  
Multicellular Interactions ◽  
Almost All ◽  
Cell Crosstalk

Intercellular communication governs multicellular interactions in complex organisms. A variety of mechanisms exist through which cells can communicate, e.g., cell-cell contact, the release of paracrine/autocrine soluble molecules, or the transfer of extracellular vesicles (EVs). EVs are membrane-surrounded structures released by almost all cell types, acting both nearby and distant from their tissue/organ of origin. In the kidney, EVs are potent intercellular messengers released by all urinary system cells and are involved in cell crosstalk, contributing to physiology and pathogenesis. Moreover, urine is a reservoir of EVs coming from the circulation after crossing the glomerular filtration barrier—or originating in the kidney. Thus, urine represents an alternative source for biomarkers in kidney-related diseases, potentially replacing standard diagnostic techniques, including kidney biopsy. This review will present an overview of EV biogenesis and classification and the leading procedures for isolating EVs from body fluids. Furthermore, their role in intra-nephron communication and their use as a diagnostic tool for precision medicine in kidney-related disorders will be discussed.

scholarly journals Truncated PPM1D Prevents Apoptosis in the Murine Thymus and Promotes Ionizing Radiation-Induced Lymphoma

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 2068
Author(s):  
Andra S. Martinikova ◽  
Monika Burocziova ◽  
Miroslav Stoyanov ◽  
Libor Macurek
Keyword(s):  
Dna Damage ◽  
Ionizing Radiation ◽  
Tumor Formation ◽  
Cell Cycle Checkpoints ◽  
Negative Regulator ◽  
Tumor Suppressor P53 ◽  
Mouse Thymus ◽  
Truncating Mutation ◽  
T Cell Lymphomas ◽  
Radiation Induced

Genome integrity is protected by the cell-cycle checkpoints that prevent cell proliferation in the presence of DNA damage and allow time for DNA repair. The transient checkpoint arrest together with cellular senescence represent an intrinsic barrier to tumorigenesis. Tumor suppressor p53 is an integral part of the checkpoints and its inactivating mutations promote cancer growth. Protein phosphatase magnesium-dependent 1 (PPM1D) is a negative regulator of p53. Although its loss impairs recovery from the G2 checkpoint and promotes induction of senescence, amplification of the PPM1D locus or gain-of-function truncating mutations of PPM1D occur in various cancers. Here we used a transgenic mouse model carrying a truncating mutation in exon 6 of PPM1D (Ppm1dT). As with human cell lines, we found that the truncated PPM1D was present at high levels in the mouse thymus. Truncated PPM1D did not affect differentiation of T-cells in the thymus but it impaired their response to ionizing radiation (IR). Thymocytes in Ppm1dT/+ mice did not arrest in the checkpoint and continued to proliferate despite the presence of DNA damage. In addition, we observed a decreased level of apoptosis in the thymi of Ppm1dT/+ mice. Moreover, the frequency of the IR-induced T-cell lymphomas increased in Ppm1dT/+Trp53+/− mice resulting in decreased survival. We conclude that truncated PPM1D partially suppresses the p53 pathway in the mouse thymus and potentiates tumor formation under the condition of a partial loss of p53 function.

scholarly journals BRAIN AND EYE AS POTENTIAL TARGETS FOR IONIZING RADIATION IMPACT. Part І. THE CONSEQUENCES OF IRRADIATION OF THE PARTICIPANTS OF THE LIQUIDATION OF THE CHORNOBYL ACCIDENT

2020 ◽  
Vol 25 ◽  
pp. 90-129
Author(s):  
K. Loganovsky ◽  
◽  
P. Fedirko ◽  
K. Kuts ◽  
D. Marazziti ◽  
...  
Keyword(s):  
Ionizing Radiation ◽  
Neurodegenerative Diseases ◽  
Nuclear Power ◽  
Radiation Effects ◽  
Radiation Risk ◽  
International Studies ◽  
Neurocognitive Deficit ◽  
Radiation Induced ◽  
And Performance ◽  
Medical Radiology

Background.Exposure to ionizing radiation could affect the brain and eyes leading to cognitive and vision impairment, behavior disorders and performance decrement during professional irradiation at medical radiology, including interventional radiological procedures, long-term space flights, and radiation accidents. Objective. The objective was to analyze the current experimental, epidemiological, and clinical data on the radiation cerebro-ophthalmic effects. Materials and methods. In our analytical review peer-reviewed publications via the bibliographic and scientometric bases PubMed / MEDLINE, Scopus, Web of Science, and selected papers from the library catalog of NRCRM – the leading institution in the field of studying the medical effects of ionizing radiation – were used. Results. The probable radiation-induced cerebro-ophthalmic effects in human adults comprise radiation cataracts, radiation glaucoma, radiation-induced optic neuropathy, retinopathies, angiopathies as well as specific neurocognitive deficit in the various neuropsychiatric pathology including cerebrovascular pathology and neurodegenerative diseases. Specific attention is paid to the likely stochastic nature of many of those effects. Those prenatally and in childhood exposed are a particular target group with a higher risk for possible radiation effects and neurodegenerative diseases. Conclusions. The experimental, clinical, epidemiological, anatomical and pathophysiological rationale for visual system and central nervous system (CNS) radiosensitivity is given. The necessity for further international studies with adequate dosimetric support and the follow-up medical and biophysical monitoring of high radiation risk cohorts is justified. The first part of the study currently being published presents the results of the study of the effects of irradiation in the participants of emergency works at the Chornobyl Nuclear Power Plant (ChNPP). Key words: ionizing radiation, cerebroophthalmic effects, neurocognitive deficit, radiation accident, radiation cataracts, macular degeneration.

scholarly journals Postprandial transfer of colostral extracellular vesicles and their protein and miRNA cargo in neonatal calves

2019 ◽  
Author(s):  
Benedikt Kirchner ◽  
Dominik Buschmann ◽  
Vijay Paul ◽  
Michael W. Pfaffl
Keyword(s):  
Extracellular Vesicles ◽  
Expression Profiles ◽  
Bovine Milk ◽  
Cell Types ◽  
Specific Protein ◽  
In Vivo Experiments ◽  
Neonatal Calves ◽  
Almost All

Abstract Background Extracellular vesicles (EVs) such as exosomes are key regulators of intercellular communication that can be found in almost all bio fluids. Although studies in the last decade have made great headway in discerning the role of EVs in many physiological and pathophysiological processes, the bioavailability and impact of dietary EVs and their cargo still remain to be elucidated. Due to its widespread consumption and high content of EV-associated microRNAs and proteins, a major focus in this field has been set on EVs in bovine milk and colostrum. Despite promising in vitro studies in recent years that show high resiliency of milk EVs to degradation and uptake of milk EV cargo in a variety of intestinal and blood cell types, in vivo experiments continue to be inconclusive and sometimes outright contradictive. Results To resolve this discrepancy, we assessed the potential postprandial transfer of colostral EVs to the circulation of newborn calves by analysing colostrum-specific protein and miRNAs, including specific isoforms (isomiRs) in cells, EV isolations and unfractionated samples from blood and colostrum. Our findings reveal distinct populations of EVs in colostrum and blood from cows that can be clearly separated by density, particle concentration and protein content (BTN1A1, MFGE8). Postprandial blood samples of calves show a time-dependent increase in EVs that share morphological and protein characteristics of colostral EVs. Analysis of miRNA expression profiles by Next-Generation Sequencing gave a different picture however. Although significant postprandial expression changes could only be detected for calf EV samples, expression profiles show very limited overlap with highly expressed miRNAs in colostral EVs or colostrum in general. Conclusions Taken together our results indicate a selective uptake of membrane-associated protein cargo but not luminal miRNAs from colostral EVs into the circulation of neonatal calves.

scholarly journals Extracellular Vesicles: An Emerging Mechanism Governing the Secretion and Biological Roles of Tenascin-C

2021 ◽  
Vol 12 ◽  
Author(s):  
Lucas Albacete-Albacete ◽  
Miguel Sánchez-Álvarez ◽  
Miguel Angel del Pozo
Keyword(s):  
Extracellular Vesicles ◽  
Molecular Mechanisms ◽  
Cell Communication ◽  
Cell Types ◽  
Target Cells ◽  
Tenascin C ◽  
Signalling Molecules ◽  
Inflammatory Processes ◽  
Bona Fide ◽  
Cellular Components

ECM composition and architecture are tightly regulated for tissue homeostasis. Different disorders have been associated to alterations in the levels of proteins such as collagens, fibronectin (FN) or tenascin-C (TnC). TnC emerges as a key regulator of multiple inflammatory processes, both during physiological tissue repair as well as pathological conditions ranging from tumor progression to cardiovascular disease. Importantly, our current understanding as to how TnC and other non-collagen ECM components are secreted has remained elusive. Extracellular vesicles (EVs) are small membrane-bound particles released to the extracellular space by most cell types, playing a key role in cell-cell communication. A broad range of cellular components can be transported by EVs (e.g. nucleic acids, lipids, signalling molecules and proteins). These cargoes can be transferred to target cells, potentially modulating their function. Recently, several extracellular matrix (ECM) proteins have been characterized as bona fide EV cargoes, exosomal secretion being particularly critical for TnC. EV-dependent ECM secretion might underpin diseases where ECM integrity is altered, establishing novel concepts in the field such as ECM nucleation over long distances, and highlighting novel opportunities for diagnostics and therapeutic intervention. Here, we review recent findings and standing questions on the molecular mechanisms governing EV–dependent ECM secretion and its potential relevance for disease, with a focus on TnC.

Abstract 533: Lymph is a Vehicle for Extracellular Vesicles in Mice

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Andreea Milasan ◽  
Nicolas Tessandier ◽  
Sisareuth Tan ◽  
Alain Brisson ◽  
Eric Boilard ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Biological Fluids ◽  
Lymphatic Vessels ◽  
The Body ◽  
Artery Wall ◽  
Waste Products ◽  
Peripheral Tissues ◽  
Cellular Debris ◽  
Long Time ◽  
Almost All

Introduction: Although for a long time considered as simple cellular debris, extracellular vesicles (EVs) are now known to be involved in many pathophysiological processes such as thrombosis, autoimmune diseases and inflammation. Due to their diversity and presence in different tissues, EVs are considered important biomarkers and thus, their precise detection in various biological fluids is important to better understand all their different functional activities. The lymphatic system works in close collaboration with the cardiovascular system to preserve fluid balance throughout the body. Lymphatic vessels are present in almost all vascularized tissues, including the brain and the artery wall, and their role in these organ-related pathologies are under intense investigations. Hypothesis: Since lymphatic vessels are often perceived as "sewers", due to their role in removing interstitial fluid and waste products from peripheral tissues such as the artery wall, we herein want to qualitatively and quantitatively assess the presence of EVs in circulating lymph. Methods and Results: Using several approaches such as a Zetasizer Nano S, electron microscopy and flow cytometry analysis, we have detected and characterized EVs in lymph of healthy animals, and found that these EVs are inclusively derived from red blood cells, platelets and lymphatic endothelial cells. Analysis of lymph from atherosclerotic mice (Ldlr -/- ) confirmed the idea that EVs number and origin varies according to the pathological setting. Conclusion: Herein, we show for the first time that EVs are present in lymph and that their level and origin vary in atherosclerosis. Our work will be setting the stage to a better understanding of the mechanism underlying EV accumulation in peripheral tissues during inflammation, and to better control related diseases.

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