Extracellular Vesicles as Innovative Tools for AssessingAdverse Effects of Immunosuppressant Drugs

2021 ◽  
Vol 28 ◽  
Author(s):  
Marianna Lucafò ◽  
Serena De Biasi ◽  
Debora Curci ◽  
Alessia Norbedo ◽  
Gabriele Stocco ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Biological Fluids ◽  
Relevant Information ◽  
Immunosuppressive Drugs ◽  
Reciprocal Interactions ◽  
Pathological Conditions ◽  
Therapeutic Uses ◽  
Donor Cells ◽  
Signal Mediators ◽  
Diagnostic And Prognostic Value

Background: Extracellular vesicles (EVs) are a heterogeneous family of small vesicles released by donor cells and absorbed by recipient cells, which represent important mediators with fundamental roles in both physiological and pathological conditions. EVs are present in a large variety of biological fluids and have a great diagnostic and prognostic value. They have gained the interest of the scientific community due to their extreme versatility. In fact, they allow us to hypothesize new therapeutic strategies since, in addition to being cell signal mediators, they play an important role as biomarkers, drug vehicles, and potential new therapeutic agents. They are also involved in immunoregulation, have the ability to transmit resistance to a drug from one cell to a more sensitive one, and can act as drug delivery systems. Objective: The main reciprocal interactions between EVs and immunosuppressive drugs will be presented. Results: The known interactions between EVs and immunosuppressive drugs, in particular, cyclosporin, glucocorticoids, rapamycin, methotrexate, cyclophosphamide, eculizumab, infliximab, certolizumab, etanercept, glatiramer acetate, and fingolimod are presented. Conclusion: This review provides relevant information on the links between EVs and immunosuppressive drugs with a focus on EVs' role as tools to assess effects of immunosuppressants, suggesting innovative properties and new possible therapeutic uses.

scholarly journals NANOmetric BIO-Banked MSC-Derived Exosome (NANOBIOME) as a Novel Approach to Regenerative Medicine

2018 ◽  
Vol 7 (10) ◽  
pp. 357 ◽  
Author(s):  
Bruna Codispoti ◽  
Massimo Marrelli ◽  
Francesco Paduano ◽  
Marco Tatullo
Keyword(s):  
Plasma Membrane ◽  
Regenerative Medicine ◽  
Extracellular Vesicles ◽  
Biological Fluids ◽  
Cell Types ◽  
Endogenous Factors ◽  
Cell Lineages ◽  
Novel Approach ◽  
Therapeutic Uses ◽  
Technical Issues

Mesenchymal stem cells (MSCs) are well known for their great potential in clinical applications. In fact, MSCs can differentiate into several cell lineages and show paracrine behavior by releasing endogenous factors that stimulate tissue repair and modulate local immune response. Each MSC type is affected by specific biobanking issues—technical issues as well as regulatory and ethical concerns—thus making it quite tricky to safely and commonly use MSC banking for swift regenerative applications. Extracellular vesicles (EVs) include a group of 150–1000 nm vesicles that are released by budding from the plasma membrane into biological fluids and/or in the culture medium from varied and heterogenic cell types. EVs consist of various vesicle types that are defined with different nomenclature such as exosomes, shedding vesicles, nanoparticles, microvesicles and apoptotic bodies. Ectosomes, micro- and nanoparticles generally refer to the direct release of single vesicles from the plasma membrane. While many studies describe exosomes as deriving from multivesicular bodies, solid evidence about the origin of EVs is often lacking. Extracellular vesicles represent an important portion of the cell secretome. Their numerous properties can be used for diagnostic, prognostic, and therapeutic uses, so EVs are considered to be innovative and smart theranostic tools. The aim of this review is to investigate the usefulness of exosomes as carriers of the whole information panel characterizing the use of MSCs in regenerative medicine. Our purpose is to make a step forward in the development of the NANOmetric BIO-banked MSC-derived Exosome (NANOBIOME).

scholarly journals Cardiac troponins in hypertension: mechanisms of increase and diagnostic value

2021 ◽  
Vol 27 (4) ◽  
pp. 390-401
Author(s):  
A. M. Chaulin ◽  
D. V. Duplyakov
Keyword(s):  
Cardiac Troponin ◽  
Prognostic Value ◽  
Biological Fluids ◽  
Diagnostic Value ◽  
Healthy Individuals ◽  
Pathological Conditions ◽  
Highly Sensitive ◽  
Protein Molecules ◽  
Diagnostic And Prognostic Value ◽  
Cardiac Troponins

The understanding of the diagnostic and prognostic value of many biomarkers of cardiovascular diseases (CVD), including cardiac troponins (cTnT and cTnI), is changing significantly with the development of methods for their determination. New highly sensitive immunoassays can detect minimal concentrations of cardiac troponin protein molecules in biological fluids (several ng/L or less), allowing the detection of cTnT and cTnI in all healthy individuals. Along with this, there are opportunities to use cTnT and cTnI both to assess the risk of developing CVD in healthy people, and to identify and monitor many early pathological conditions that pose a risk to the cardiovascular system and the life of patients. These pathological conditions include hypertension (HTN), which is the direct cause leading to coronary heart disease, acute myocardial infarction, stroke, and other CVD. A number of recent studies reported the possibility of using highly sensitive cTnT and cTnI in the management of HTN patients. In this article, we consider in detail the diagnostic and prognostic value of cardiac troponins in HTN, we also discuss the main possible mechanisms underlying the increase in cTnT and cTnI in human body fluids.

scholarly journals Cardiac troponins in hypertension: mechanisms of increase and diagnostic value

2021 ◽  
Vol 27 (4) ◽  
pp. 390-401
Author(s):  
A. M. Chaulin ◽  
D. V. Duplyakov
Keyword(s):  
Cardiac Troponin ◽  
Prognostic Value ◽  
Biological Fluids ◽  
Diagnostic Value ◽  
Healthy Individuals ◽  
Pathological Conditions ◽  
Highly Sensitive ◽  
Protein Molecules ◽  
Diagnostic And Prognostic Value ◽  
Cardiac Troponins

The understanding of the diagnostic and prognostic value of many biomarkers of cardiovascular diseases (CVD), including cardiac troponins (cTnT and cTnI), is changing significantly with the development of methods for their determination. New highly sensitive immunoassays can detect minimal concentrations of cardiac troponin protein molecules in biological fluids (several ng/L or less), allowing the detection of cTnT and cTnI in all healthy individuals. Along with this, there are opportunities to use cTnT and cTnI both to assess the risk of developing CVD in healthy people, and to identify and monitor many early pathological conditions that pose a risk to the cardiovascular system and the life of patients. These pathological conditions include hypertension (HTN), which is the direct cause leading to coronary heart disease, acute myocardial infarction, stroke, and other CVD. A number of recent studies reported the possibility of using highly sensitive cTnT and cTnI in the management of HTN patients. In this article, we consider in detail the diagnostic and prognostic value of cardiac troponins in HTN, we also discuss the main possible mechanisms underlying the increase in cTnT and cTnI in human body fluids.

Separation of Extracellular Vesicles by DNA-Directed Immunocapturing Followed by Enzymatic Release

2020 ◽  
Author(s):  
Dario Brambilla ◽  
Laura Sola ◽  
Elisa Chiodi ◽  
Natasa Zarovni ◽  
Diogo Fortunato ◽  
...  
Keyword(s):  
Cell Culture ◽  
Extracellular Vesicles ◽  
Culture Media ◽  
Biological Fluids ◽  
Imaging Techniques ◽  
Cell Communication ◽  
Disease Diagnosis ◽  
Cell Culture Supernatant ◽  
Transmission Electron ◽  
Downstream Analysis

Extracellular vesicles (EVs) have attracted great interest among researchers due to their role in cell-cell communication, disease diagnosis, and drug delivery. In spite of their potential in the medical field, there is no consensus on the best method for separating microvesicles from cell culture supernatant and complex biological fluids. Obtaining a good recovery yield and preserving physical characteristics is critical for the diagnostic and therapeutic use of EVs. The separation is made complex by the fact that blood and cell culture media, contain a large number of nanoparticles in the same size range. Methods that exploit immunoaffinity capture provide high purity samples and overcome the issues of currently used separation methods. However, the release of captured nanovesicles requires harsh conditions that hinder their use in certain types of downstream analysis. Herein, a novel capture and release approach for small extracellular vesicles (sEVs), based on DNAdirected immobilization of antiCD63 antibody is presented. The flexible DNAlinker increases the capture efficiency and allows releasing of EVs by exploiting the endonucleasic activity of DNAse I. This separation protocol works under mild conditions, enabling the release of intact vesicles that can be successfully analyzed by imaging techniques. In this article sEVs recovered from plasma were characterized by established techniques for EVs analysis including nanoparticle tracking and transmission electron microscopy.<br>

scholarly journals The Role of Extracellular Vesicles as Shuttles of RNA and Their Clinical Significance as Biomarkers in Hepatocellular Carcinoma

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 902
Author(s):  
Eva Costanzi ◽  
Carolina Simioni ◽  
Gabriele Varano ◽  
Cinzia Brenna ◽  
Ilaria Conti ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Extracellular Vesicles ◽  
Tumor Metastasis ◽  
Biological Processes ◽  
Rna Molecules ◽  
Expression Of Genes ◽  
Non Coding Rna ◽  
Donor Cells ◽  
Relevant Role

Extracellular vesicles (EVs) have attracted interest as mediators of intercellular communication following the discovery that EVs contain RNA molecules, including non-coding RNA (ncRNA). Growing evidence for the enrichment of peculiar RNA species in specific EV subtypes has been demonstrated. ncRNAs, transferred from donor cells to recipient cells, confer to EVs the feature to regulate the expression of genes involved in differentiation, proliferation, apoptosis, and other biological processes. These multiple actions require accuracy in the isolation of RNA content from EVs and the methodologies used play a relevant role. In liver, EVs play a crucial role in regulating cell–cell communications and several pathophysiological events in the heterogeneous liver class of cells via horizontal transfer of their cargo. This review aims to discuss the rising role of EVs and their ncRNAs content in regulating specific aspects of hepatocellular carcinoma development, including tumorigenesis, angiogenesis, and tumor metastasis. We analyze the progress in EV-ncRNAs’ potential clinical applications as important diagnostic and prognostic biomarkers for liver conditions.

scholarly journals Extracellular Vesicles: Novel Opportunities to Understand and Detect Neoplastic Diseases

2021 ◽  
pp. 030098582199932
Author(s):  
Laura Bongiovanni ◽  
Anneloes Andriessen ◽  
Marca H. M. Wauben ◽  
Esther N. M. Nolte-’t Hoen ◽  
Alain de Bruin
Keyword(s):  
Extracellular Vesicles ◽  
Biologically Active ◽  
Liquid Biopsies ◽  
Donor Cells ◽  
Recent Developments ◽  
Veterinary Pathology ◽  
Cell Components ◽  
Potential Applications ◽  
Intercellular Communications

With a size range from 30 to 1000 nm, extracellular vesicles (EVs) are one of the smallest cell components able to transport biologically active molecules. They mediate intercellular communications and play a fundamental role in the maintenance of tissue homeostasis and pathogenesis in several types of diseases. In particular, EVs actively contribute to cancer initiation and progression, and there is emerging understanding of their role in creation of the metastatic niche. This fact underlies the recent exponential growth in EV research, which has improved our understanding of their specific roles in disease and their potential applications in diagnosis and therapy. EVs and their biomolecular cargo reflect the state of the diseased donor cells, and can be detected in body fluids and exploited as biomarkers in cancer and other diseases. Relatively few studies have been published on EVs in the veterinary field. This review provides an overview of the features and biology of EVs as well as recent developments in EV research including techniques for isolation and analysis, and will address the way in which the EVs released by diseased tissues can be studied and exploited in the field of veterinary pathology. Uniquely, this review emphasizes the important contribution that pathologists can make to the field of EV research: pathologists can help EV scientists in studying and confirming the role of EVs and their molecular cargo in diseased tissues and as biomarkers in liquid biopsies.

scholarly journals Extracellular Vesicles and Matrix Remodeling Enzymes: The Emerging Roles in Extracellular Matrix Remodeling, Progression of Diseases and Tissue Repair

Cells ◽  
2018 ◽  
Vol 7 (10) ◽  
pp. 167 ◽  
Author(s):  
Muhammad Nawaz ◽  
Neelam Shah ◽  
Bruna Zanetti ◽  
Marco Maugeri ◽  
Renata Silvestre ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Extracellular Vesicles ◽  
Tissue Repair ◽  
Metabolic Diseases ◽  
Bioactive Molecules ◽  
Tissue Inhibitors Of Metalloproteinases ◽  
Matrix Remodeling ◽  
Pathological Conditions ◽  
Potential Applications ◽  
Non Coding Rnas

Extracellular vesicles (EVs) are membrane enclosed micro- and nano-sized vesicles that are secreted from almost every species, ranging from prokaryotes to eukaryotes, and from almost every cell type studied so far. EVs contain repertoire of bioactive molecules such as proteins (including enzymes and transcriptional factors), lipids, carbohydrates and nucleic acids including DNA, coding and non-coding RNAs. The secreted EVs are taken up by neighboring cells where they release their content in recipient cells, or can sail through body fluids to reach distant organs. Since EVs transport bioactive cargo between cells, they have emerged as novel mediators of extra- and intercellular activities in local microenvironment and inter-organ communications distantly. Herein, we review the activities of EV-associated matrix-remodeling enzymes such as matrix metalloproteinases, heparanases, hyaluronidases, aggrecanases, and their regulators such as extracellular matrix metalloproteinase inducers and tissue inhibitors of metalloproteinases as novel means of matrix remodeling in physiological and pathological conditions. We discuss how such EVs act as novel mediators of extracellular matrix degradation to prepare a permissive environment for various pathological conditions such as cancer, cardiovascular diseases, arthritis and metabolic diseases. Additionally, the roles of EV-mediated matrix remodeling in tissue repair and their potential applications as organ therapies have been reviewed. Collectively, this knowledge could benefit the development of new approaches for tissue engineering.

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.

Zika virus hijacks extracellular vesicle tetraspanin pathways for cell-to-cell transmission

2021 ◽  
Author(s):  
Sara B. York ◽  
Li Sun ◽  
Allaura S. Cone ◽  
Leanne C. Duke ◽  
Mujeeb R. Cheerathodi ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Intercellular Communication ◽  
Zika Virus ◽  
Biological Fluids ◽  
Virus Transmission ◽  
First Trimester ◽  
Enhanced Production ◽  
Infected Cells ◽  
Encapsulated Structures

ABSTRACTExtracellular vesicles (EVs) are membrane-encapsulated structures released by cells which carry signaling factors, proteins and microRNAs that mediate intercellular communication. Accumulating evidence supports an important role of EVs in the progression of neurological conditions and both the spread and pathogenesis of infectious diseases. It has recently been demonstrated that EVs from Hepatitis C virus (HCV) infected individuals and cells contained replicative-competent viral RNA that was capable of infecting hepatocytes. Being a member of the same viral family, it is likely the Zika virus also hijacks EV pathways to package viral components and secrete vesicles that are infectious and potentially less immunogenic. As EVs have been shown to cross blood-brain and placental barriers, it is possible that Zika virus could usurp normal EV biology to gain access to the brain or developing fetus. Here, we demonstrate that Zika virus infected cells secrete distinct EV sub-populations with specific viral protein profiles and infectious genomes. Zika virus infection resulted in the enhanced production of EVs with varying sizes and density compared to those released from non-infected cells. We also show that the EV enriched tetraspanin CD63 regulates the release of EVs, and Zika viral genomes and capsids following infection. Overall, these findings provide evidence for an alternative means of Zika virus transmission and demonstrate the role of EV biogenesis and trafficking proteins in the modulation of Zika infection.ImportanceZika virus is a re-emerging infectious disease that spread rapidly across the Caribbean and South America. Infection of pregnant women during the first trimester has been linked to microcephaly, a neurological condition where babies are born with smaller heads due to abnormal brain development. Babies born with microcephaly can develop convulsions and suffer disabilities as they age. Despite the significance of Zika virus, little is known about how the virus infects the fetus or causes disease. Extracellular vesicles (EVs) are membrane-encapsulated structures released by cells that are present in all biological fluids. EVs carry signaling factors, proteins and microRNAs that mediate intercellular communication. EVs have been shown to be a means by which some viruses can alter cellular environments and cross previously unpassable cellular barriers. Thus gaining a greater understanding of how Zika affects EV cargo may aid in the development of better diagnostics, targeted therapeutics and prophylactic treatments.

scholarly journals Platelet Extracellular Vesicles

2020 ◽  
Author(s):  
Florian Puhm ◽  
Eric Boilard ◽  
Kellie R. Machlus
Keyword(s):  
Bone Marrow ◽  
Synovial Fluid ◽  
Nucleic Acids ◽  
Extracellular Vesicles ◽  
Cell Communication ◽  
Biological Processes ◽  
Vascular Integrity ◽  
Pathological Conditions ◽  
Broad Array

Extracellular vesicles (EVs) are a means of cell-to-cell communication and can facilitate the exchange of a broad array of molecules between adjacent or distant cells. Platelets are anucleate cells derived from megakaryocytes and are primarily known for their role in maintaining hemostasis and vascular integrity. Upon activation by a variety of agonists, platelets readily generate EVs, which were initially identified as procoagulant particles. However, as both platelets and their EVs are abundant in blood, the role of platelet EVs in hemostasis may be redundant. Moreover, findings have challenged the significance of platelet-derived EVs in coagulation. Looking beyond hemostasis, platelet EV cargo is incredibly diverse and can include lipids, proteins, nucleic acids, and organelles involved in numerous other biological processes. Furthermore, while platelets cannot cross tissue barriers, their EVs can enter lymph, bone marrow, and synovial fluid. This allows for the transfer of platelet-derived content to cellular recipients and organs inaccessible to platelets. This review highlights the importance of platelet-derived EVs in physiological and pathological conditions beyond hemostasis.

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