scholarly journals From Tumor Metastasis towards Cerebral Ischemia—Extracellular Vesicles as a General Concept of Intercellular Communication Processes

2019 ◽  
Vol 20 (23) ◽  
pp. 5995 ◽  
Author(s):  
Xuan Zheng ◽  
Mathias Bähr ◽  
Thorsten R. Doeppner
Keyword(s):  
Cerebral Ischemia ◽  
Extracellular Vesicles ◽  
Intercellular Communication ◽  
Short Review ◽  
General Concept ◽  
Tumor Formation ◽  
Pathological Conditions ◽  
Communication Processes ◽  
Reported Data

Extracellular vesicles (EVs) have been tremendous carriers in both experimental and translational science. These vesicles—formerly regarded as artifacts of in vitro research—have a heterogeneous population of vesicles derived from virtually all eukaryotic cells. EVs consist of a bilayer lipid structure with a diameter of about 30 to 1000 nm and have a characteristic protein and non-coding RNA content that make up different forms of EVs such as exosomes, microvesicles, and others. Despite recent progress in the EV field, which is known to serve as potential biomarkers and therapeutic tools under various pathological conditions, fundamental questions are yet to be answered. This short review focuses on recently reported data regarding EVs under pathological conditions with a particular emphasis on the role of EVs under such different conditions like tumor formation and cerebral ischemia. The review strives to point out general concepts of EV intercellular communication processes that might be vital to both diagnostic and therapeutic strategies in the long run.

scholarly journals Extracellular vesicles as mediators and markers of acute organ injury: current concepts

2021 ◽  
Author(s):  
Birte Weber ◽  
Niklas Franz ◽  
Ingo Marzi ◽  
Dirk Henrich ◽  
Liudmila Leppik
Keyword(s):  
Extracellular Vesicles ◽  
Inflammatory Diseases ◽  
Organ Injury ◽  
Isolation And Characterization ◽  
Communication Processes ◽  
Incidence And Mortality ◽  
New Biomarkers ◽  
And Function

AbstractDue to the continued high incidence and mortality rate worldwide, there is a need to develop new strategies for the quick, precise, and valuable recognition of presenting injury pattern in traumatized and poly-traumatized patients. Extracellular vesicles (EVs) have been shown to facilitate intercellular communication processes between cells in close proximity as well as distant cells in healthy and disease organisms. miRNAs and proteins transferred by EVs play biological roles in maintaining normal organ structure and function under physiological conditions. In pathological conditions, EVs change the miRNAs and protein cargo composition, mediating or suppressing the injury consequences. Therefore, incorporating EVs with their unique protein and miRNAs signature into the list of promising new biomarkers is a logical next step. In this review, we discuss the general characteristics and technical aspects of EVs isolation and characterization. We discuss results of recent in vitro, in vivo, and patients study describing the role of EVs in different inflammatory diseases and traumatic organ injuries. miRNAs and protein signature of EVs found in patients with acute organ injury are also debated.

scholarly journals Emerging role of extracellular vesicles in the regulation of skeletal muscle adaptation

2019 ◽  
Vol 127 (2) ◽  
pp. 645-653 ◽  
Author(s):  
Ivan J. Vechetti
Keyword(s):  
Skeletal Muscle ◽  
Extracellular Vesicles ◽  
Human Body ◽  
Intercellular Communication ◽  
Skeletal Muscle Mass ◽  
Genetic Material ◽  
Muscle Adaptation ◽  
Pathological Conditions ◽  
Isolation Methods

Extracellular vesicles (EVs) were initially characterized as “garbage bags” with the purpose of removing unwanted material from cells. It is now becoming clear that EVs mediate intercellular communication between distant cells through a transfer of genetic material, a process important to the systemic adaptation in physiological and pathological conditions. Although speculative, it has been suggested that the majority of EVs that make it into the bloodstream would be coming from skeletal muscle, since it is one of the largest organs in the human body. Although it is well established that skeletal muscle secretes peptides (currently known as myokines) into the bloodstream, the notion that skeletal muscle releases EVs is in its infancy. Besides intercellular communication and systemic adaptation, EV release could represent the mechanism by which muscle adapts to certain stimuli. This review summarizes the current understanding of EV biology and biogenesis and current isolation methods and briefly discusses the possible role EVs have in regulating skeletal muscle mass.

scholarly journals Extracellular vesicles therapy: opportunities, mechanisms and perspectives

2020 ◽  
Vol 25 (10) ◽  
pp. 4081
Author(s):  
F. S. Velikonivtsev ◽  
A. S. Golovkin
Keyword(s):  
Extracellular Vesicles ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Biological Membrane ◽  
Biologically Active ◽  
Therapeutic Approaches ◽  
Pathological Conditions ◽  
Clinical Conditions ◽  
Intercellular Communications

Extracellular vesicles are biological membrane-coated objects with size less then 1000 nm. They can contain variety of biologically active molecules (such as proteins, miRNA, mRNA, DNA etc.) and also are able to provide intercellular communications and implement lots if biological functions. Now possibilities of using extracellular vesicles for therapeutic approaches against various diseases and pathological conditions are rapidly discovered. In the most of cases mesenchymal stem cells are the sources of extracellular vesicles and miRNAs which vesicles transport are considered to be causable agents of their activities. In-vitro studies show that extracellular vesicles provide anti-inflammatory, anti-apoptotic activities and can stimulate angiogenesis and regeneration. Performed studies which were analyzed and structurized by us in this review demonstrate current perspectives for clinical use of extracellular vesicles in the therapy of such clinical conditions as oxidative stress, ischemia-reperfusion injury, tumor growth etc.

scholarly journals Extracellular Vesicles: Intercellular Communication Mediators in Antiphospholipid Syndrome

2021 ◽  
Author(s):  
Ula Štok ◽  
Saša Čučnik ◽  
Snežna Sodin-Šemrl ◽  
Polona Žigon
Keyword(s):  
Extracellular Vesicles ◽  
Antiphospholipid Syndrome ◽  
Intercellular Communication ◽  
Systemic Autoimmune Disease ◽  
In Vivo Models ◽  
Isolation And Characterization ◽  
Increased Risk ◽  
Insight Into

Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by thrombosis, obstetric complications and the presence of antiphospholipid antibodies (aPL) that cause endothelial injury and thrombophilia. Extracellular vesicles are involved in endothelial and thrombotic pathologies and may therefore have an influence on the prothrombotic status of APS patients. Intercellular communication and connectivity are important mechanisms of interaction between healthy and pathologically altered cells. Despite well-characterized in vitro and in vivo models of APS pathology, the field of extracellular vesicles is still largely unexplored and could therefore provide an insight into the APS mechanism and possibly serve as a biomarker to identify patients at increased risk. The analysis of EVs poses a challenge due to the lack of standardized technology for their isolation and characterization. Recent findings in the field of EVs offer promising aspects that may explain their role in the pathogenesis of various diseases, including APS.

scholarly journals Circulating Extracellular Vesicles from Patients with Sickle Cell Disease Progressively Disrupt Different Types of Endothelial Intercellular Junctions

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4823-4823
Author(s):  
Gabrielle Lapping-Carr ◽  
Joanna Gemel ◽  
Yifan Mao ◽  
Eric C. Beyer
Keyword(s):  
Plasma Membrane ◽  
Sickle Cell Disease ◽  
Gap Junctions ◽  
Extracellular Vesicles ◽  
Sickle Cell ◽  
Intercellular Communication ◽  
Cell Disease ◽  
Endothelial Monolayer ◽  
Cell Cell

Introduction: Aberrant cell-cell interactions involving the endothelium are central to the pathophysiology of crises in sickle cell disease (SCD), including acute chest syndrome (ACS). We previously demonstrated that the plasma of SCD patients contains circulating small extracellular vesicles (EVs) and that those vesicles can disrupt endothelial integrity in vitro, including a decrease in VE-cadherin. The current study was designed to examine the effects of those EVs on additional components of the endothelial junctions including tight (zonula occludens 1, ZO-1) and gap junctions (connexin43, Cx43) and to test the hypothesis that the junctions would be more severely affected by EVs isolated from patients during an episode of ACS than by those isolated from the same patient at baseline. Methods: We identified subjects with SCD in our biobank who had plasma isolated at baseline and at the beginning of an admission for ACS (prior to transfusion). Samples were considered baseline if the patient was more than 4 weeks since transfusion and had no new health-related complaints. ACS was defined by the presence of an infiltrate on chest x-ray combined with fever, pain, hypoxia or cough. EVs were isolated from plasma using established methodologies. To determine the effects on endothelium, cultures of human microvascular endothelial cells were treated with EVs for 48 h. Cells were fixed and studied by fluorescence microscopy (after immunolocalization of Cx43, ZO-1 and/or VE-cadherin and staining of nuclei with DAPI). Proteins were detected and quantified by immunoblotting. mRNA expression was determined by RT-qPCR. Gap junction mediated intercellular communication was assessed following microinjection of Lucifer yellow and neurobiotin. Results: Microscopy confirmed our previous observation that EVs isolated from subjects with SCD caused in vitro disruption of endothelial monolayers and that damage is significantly worse when EVs are isolated during an episode of ACS. The distribution and abundance of VE-cadherin and ZO-1 at the plasma membrane of undisturbed cells were minimally affected by SCD EVs. While baseline EVs did not detectably affect the distribution of Cx43, EVs isolated during ACS caused a loss of Cx43 from the plasma membrane. The integrated intensity of Cx43 membrane staining was decreased by ~20% following treatment with ACS EVs. Cx43 protein decreased on average by 32 % and Cx43 mRNA levels by 21% in cells treated with ACS EVs compared to baseline from the same patient. EVs isolated during ACS caused significant disruption in intercellular transfer compared to EVs isolated at baseline (67-94% reduction) (Figure 1). Conclusions: Our results show that subjects with SCD produce small EVs that cause disruption of the endothelial monolayer in vitro. Gap junctions composed of Cx43 are the most sensitive of the cell-cell junctions in this setting, since their abundance and function are reduced by ACS EVs even when the endothelial monolayer appears intact. Disruption of endothelial intercellular communication mediated by Cx43 appears to be an early and sensitive event in the endothelial disturbance caused by EVs in SCD patients. Disclosures No relevant conflicts of interest to declare.

scholarly journals Navigating the Landscape of Tumor Extracellular Vesicle Heterogeneity

2019 ◽  
Vol 20 (6) ◽  
pp. 1349 ◽  
Author(s):  
Sabrina Roy ◽  
Hsing-Ying Lin ◽  
Chung-Yu Chou ◽  
Chen-Han Huang ◽  
Julia Small ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Intercellular Communication ◽  
Extracellular Vesicle ◽  
Rapid Expansion ◽  
Parent Cell ◽  
Membrane Composition ◽  
Pathological Conditions ◽  
Respective Parent ◽  
Experimental Level

The last decade has seen a rapid expansion of interest in extracellular vesicles (EVs) released by cells and proposed to mediate intercellular communication in physiological and pathological conditions. Considering that the genetic content of EVs reflects that of their respective parent cell, many researchers have proposed EVs as a source of biomarkers in various diseases. So far, the question of heterogeneity in given EV samples is rarely addressed at the experimental level. Because of their relatively small size, EVs are difficult to reliably isolate and detect within a given sample. Consequently, standardized protocols that have been optimized for accurate characterization of EVs are lacking despite recent advancements in the field. Continuous improvements in pre-analytical parameters permit more efficient assessment of EVs, however, methods to more objectively distinguish EVs from background, and to interpret multiple single-EV parameters are lacking. Here, we review EV heterogeneity according to their origin, mode of release, membrane composition, organelle and biochemical content, and other factors. In doing so, we also provide an overview of currently available and potentially applicable methods for single EV analysis. Finally, we examine the latest findings from experiments that have analyzed the issue at the single EV level and discuss potential implications.

scholarly journals The role of the metabolite cargo of extracellular vesicles in tumor progression

2021 ◽  
Author(s):  
Mária Harmati ◽  
Mátyás Bukva ◽  
Tímea Böröczky ◽  
Krisztina Buzás ◽  
Edina Gyukity-Sebestyén
Keyword(s):  
Tumor Progression ◽  
Extracellular Vesicles ◽  
Biomarker Discovery ◽  
Tumor Development ◽  
Living Cells ◽  
Pathological Conditions ◽  
Membrane Bound ◽  
And Function

AbstractMetabolomic reprogramming in tumor and stroma cells is a hallmark of cancer but understanding its effects on the metabolite composition and function of tumor-derived extracellular vesicles (EVs) is still in its infancy. EVs are membrane-bound sacs with a complex molecular composition secreted by all living cells. They are key mediators of intercellular communication both in normal and pathological conditions and play a crucial role in tumor development. Although lipids are major components of EVs, most of the EV cargo studies have targeted proteins and nucleic acids. The potential of the EV metabolome as a source for biomarker discovery has gained recognition recently, but knowledge on the biological activity of tumor EV metabolites still remains limited. Therefore, we aimed (i) to compile the list of metabolites identified in tumor EVs isolated from either clinical specimens or in vitro samples and (ii) describe their role in tumor progression through literature search and pathway analysis.

scholarly journals Extracellular Vesicles as Natural Delivery Carriers Regulate Oxidative Stress Under Pathological Conditions

2021 ◽  
Vol 9 ◽  
Author(s):  
Hongzhao Qi ◽  
Yingruo Wang ◽  
Shunxin Fa ◽  
Changqing Yuan ◽  
Lijun Yang
Keyword(s):  
Oxidative Stress ◽  
Extracellular Vesicles ◽  
Indirect Effects ◽  
Short Review ◽  
The Other ◽  
Direct Effects ◽  
Pathological Conditions ◽  
Physiological Phenomenon ◽  
The One ◽  
All Diseases

Extracellular vesicles are cellular secretory particles that can be used as natural drug delivery carriers. They have successfully delivered drugs including chemotherapeutics, proteins, and genes to treat various diseases. Oxidative stress is an abnormal physiological phenomenon, and it is associated with nearly all diseases. In this short review, we summarize the regulation of EVs on oxidative stress. There are direct effects and indirect effects on the regulation of oxidative stress through EVs. On the one hand, they can deliver antioxidant substances or oxides to recipient cells, directly relieving or aggravating oxidative stress. On the other hand, regulate factors of oxidative stress-related signaling pathways can be delivered to recipient cells by the mediation of EVs, realizing the indirect regulation of oxidative stress. To the best of our knowledge, however, only endogenous drugs have been delivered by EVs to regulate oxidative stress till now. And the heterogeneity of EVs may complicate the regulation of oxidative stress. Therefore, this short review aims to draw more attention to the EVs-based regulation of oxidative stress, and we hope excellent EVs-based delivery carriers that can deliver exogenous drugs to regulate oxidative stress can be exploited.

A Systematic Review on Extracellular Vesicles-Enriched Fat Grafting: A Shifting Paradigm

2020 ◽  
Author(s):  
Mohammad Ghiasloo ◽  
Laura De Wilde ◽  
Kashika Singh ◽  
Patrick Tonnard ◽  
Alexis Verpaele ◽  
...  
Keyword(s):  
Systematic Review ◽  
Graft Survival ◽  
Extracellular Vesicles ◽  
Retention Rate ◽  
Fat Grafting ◽  
Retention Rates ◽  
Fat Graft ◽  
Cochrane Central Register

Abstract Background Recent evidence confirms that mesenchymal stem cells (MSCs) facilitate angiogenesis mainly through paracrine function. Extracellular vesicles (EVs) are regarded as key components of the cell secretome, possessing functional properties of their source cells. Subsequently, MSC-EVs have emerged as a novel cell-free approach to improve fat graft retention rate. Objectives To provide a systematic review of all studies reporting the use of MSC-EVs to improve graft retention rate. Methods A systematic search was undertaken using the Embase, PubMed and the Cochrane Central Register of Controlled Trials databases. Outcome measures included donor/receptor organism of the fat graft, study model, intervention groups, evaluation intervals, EV research data, in vitro and in vivo results. Results Of the total 1717 articles, 62 full-texts were screened. Seven studies reporting on 294mice were included. Overall, EV treated groups showed higher graft retention rates compared to untreated groups. Notably, retention rate was similar following EV- and MSC-treatment. In addition to reduced inflammation, graft enrichment with EVs resulted in early revascularization and better graft integrity. Interestingly, hypoxic preconditioning of MSCs improved their beneficial paracrine effects and led to a more proangiogenic EV population, as observed by both in vitro and in vivo results. Conclusions MSC-EVs appear to offer an interesting cell-free alternative to improve fat graft survival. While their clinical relevance remains to be determined, it is clear that not the cells, but their secretome is essential for graft survival. Thus, a paradigm shift from cell-assisted lipotransfer towards ‘secretome-assisted lipotransfer’ is well on its way.

scholarly journals Albumin in patients with liver disease shows an altered conformation

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Margret Paar ◽  
Vera H. Fengler ◽  
Daniel J. Rosenberg ◽  
Angelika Krebs ◽  
Rudolf E. Stauber ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Liver Disease ◽  
Chronic Liver Disease ◽  
Chronic Liver ◽  
X Ray Scattering ◽  
Pathological Conditions ◽  
Healthy Donors ◽  
Relevant Variables ◽  
End Stage

AbstractHuman serum albumin (HSA) constitutes the primary transporter of fatty acids, bilirubin, and other plasma compounds. The binding, transport, and release of its cargos strongly depend on albumin conformation, which is affected by bound ligands induced by physiological and pathological conditions. HSA is both highly oxidized and heavily loaded with fatty acids and bilirubin in chronic liver disease. By employing small-angle X-ray scattering we show that HSA from the plasma of chronic liver disease patients undergoes a distinct opening compared to healthy donors. The extent of HSA opening correlates with clinically relevant variables, such as the model of end-stage liver disease score, bilirubin, and fatty acid levels. Although the mild oxidation of HSA in vitro does not alter overall structure, the alteration of patients’ HSA correlates with its redox state. This study connects clinical data with structural visualization of albumin dynamicity in solution and underlines the functional importance of albumin’s inherent flexibility.

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