scholarly journals Beyond the Extracellular Vesicles: Technical Hurdles, Achieved Goals and Current Challenges When Working on Adipose Cells

2021 ◽  
Vol 22 (7) ◽  
pp. 3362
Author(s):  
María Gómez-Serrano ◽  
Viviane Ponath ◽  
Christian Preußer ◽  
Elke Pogge von Strandmann
Keyword(s):  
Extracellular Vesicles ◽  
Cell Communication ◽  
Special Focus ◽  
Entire Body ◽  
Main Cell ◽  
Systemic Level ◽  
Main Cell Type ◽  
Methodological Approaches ◽  
Adipose Cells

Adipose tissue and its crosstalk with other organs plays an essential role in the metabolic homeostasis of the entire body. Alteration of this communication (i.e., due to obesity) is related to the development of several comorbidities including type 2 diabetes, cardiovascular diseases, or cancer. Within the adipose depot, adipocytes are the main cell type and thus the main source of secreted molecules, which exert modulating effects not only at a local but also at a systemic level. Extracellular vesicles (EVs) have recently emerged as important mediators in cell–cell communication and account for part of the cellular secretome. In recent years, there has been a growing body of research on adipocyte-derived extracellular vesicles (Ad-EVs). However, there is still a lack of standardized methodological approaches, especially regarding primary adipocytes. In this review, we will provide an outline of crucial aspects when working on adipose-derived material, with a special focus on primary adipocytes. In parallel, we will point out current methodological challenges in the EV field and how they impact the transcriptomic, proteomic and functional evaluations of Ad-EVs.

scholarly journals In Vivo Tracking of Extracellular Vesicles by Nuclear Imaging: Advances in Radiolabeling Strategies

2020 ◽  
Vol 21 (24) ◽  
pp. 9443
Author(s):  
Sara Almeida ◽  
Liliana Santos ◽  
Amílcar Falcão ◽  
Célia Gomes ◽  
Antero Abrunhosa
Keyword(s):  
Extracellular Vesicles ◽  
Covalent Binding ◽  
Cell Communication ◽  
Nuclear Imaging ◽  
High Sensitivity ◽  
Imaging Modalities ◽  
Biological Behavior ◽  
Imaging Biomarkers ◽  
Special Focus

Extracellular vesicles (EVs) are naturally secreted vesicles that have attracted a large amount of interest in nanomedicine in recent years due to their innate biocompatibility, high stability, low immunogenicity, and important role in cell-to-cell communication during pathological processes. Their versatile nature holds great potential to improve the treatment of several diseases through their use as imaging biomarkers, therapeutic agents, and drug-delivery vehicles. However, the clinical translation of EV-based approaches requires a better understanding of their in vivo behavior. Several imaging technologies have been used for the non-invasive in vivo tracking of EVs, with a particular emphasis on nuclear imaging due to its high sensitivity, unlimited penetration depth and accurate quantification. In this article, we will review the biological function and inherent characteristics of EVs and provide an overview of molecular imaging modalities used for their in vivo monitoring, with a special focus on nuclear imaging. The advantages of radionuclide-based imaging modalities make them a promising tool to validate the use of EVs in the clinical setting, as they have the potential to characterize in vivo the pharmacokinetics and biological behavior of the vesicles. Furthermore, we will discuss the current methods available for radiolabeling EVs, such as covalent binding, encapsulation or intraluminal labeling and membrane radiolabeling, reporting the advantages and drawbacks of each radiolabeling approach.

Messages From the Small Intestine Carried by Extracellular Vesicles in Prediabetes: a Proteomic Portrait

2021 ◽  
Author(s):  
Inês Ferreira ◽  
Rita Machado de Oliveira ◽  
Ana Sofia Carvalho ◽  
Hans Christian Beck ◽  
Rune Matthiesen ◽  
...  
Keyword(s):  
Small Intestine ◽  
Extracellular Vesicles ◽  
Cell Communication ◽  
The Body ◽  
Gut Dysbiosis ◽  
Pathological Conditions ◽  
Glycolytic Activity ◽  
Mediate Cell ◽  
Metabolic Dysfunctions

AbstractExtracellular vesicles (EVs) mediate cell-cell communication in a variety of physiological and pathological conditions. In the pathogenesis of type 2 diabetes, inter-organ communication plays an important role in its progress and metabolic surgery leads to its remission. Gut dysbiosis is emerging as a diabetogenic factor. However, it remains unclear how gut senses metabolic alterations and whether this is transmitted to other tissues via EVs content. In this study, using a diet induced-prediabetic mouse model, we observed that protein packaging in gut derived extracellular vesicles (GDE), specifically at the small intestine, is increased in prediabetes compared to GDE from healthy mice. Moreover, there were significant differences in GDE proteins between the two conditions. Proteins related to lipid metabolism and to oxidative stress management were more abundant in prediabetic GDE compared to those of healthy mice. On the other hand, proteins related to glycolytic activity, as well as those responsible for the degradation of polyubiquitinated composites in the proteasome, were depleted in prediabetic GDE compared to those of healthy mice. Together, our findings show that protein packaging in GDE is markedly modified during prediabetes pathogenesis. Thus, suggesting that prediabetes alterations in small intestine are translated into GDE with a modified protein cargo which are dispersed into the circulation where they can interact with and influence the metabolic status of other tissues. This study highlights the importance of the small intestine as a tissue that can propagate the metabolic dysfunctions of prediabetes throughout the body and the importance of GDE as the messenger.

2117-P: Biomarkers Isolated from Extracellular Vesicles Prior to Bariatric Surgery May Be Associated with Postoperative Resolution of Type 2 Diabetes

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 2117-P
Author(s):  
REBECCA HILLYER ◽  
TRAVIS SULLIVAN ◽  
KIMBERLY CHRIST ◽  
AMEYA HODARKAR ◽  
MARY BETH HODGE
Keyword(s):  
Type 2 Diabetes ◽  
Bariatric Surgery ◽  
Extracellular Vesicles

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 Multiple Roles of Exosomal Long Noncoding RNAs in Cancers

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Wenyuan Zhao ◽  
Yuanqi Liu ◽  
Chunfang Zhang ◽  
Chaojun Duan
Keyword(s):  
Extracellular Vesicles ◽  
Cancer Diagnosis ◽  
Tumor Angiogenesis ◽  
Cell Communication ◽  
Noncoding Rnas ◽  
Multiple Roles ◽  
Long Noncoding Rnas ◽  
Cancer Therapies ◽  
Transcriptional Noise ◽  
Intercellular Exchange

Long noncoding RNAs (lncRNAs) are not transcriptional noise, as previously understood, but are currently considered to be multifunctional. Exosomes are derived from the internal multivesicular compartment and are extracellular vesicles (EVs) with diameters of 30–100 nm. Exosomes play significant roles in the intercellular exchange of information and material. Exosomal lncRNAs may be promising biomarkers for cancer diagnosis and potential targets for cancer therapies, since they are increasingly understood to be involved in tumorigenesis, tumor angiogenesis, and chemoresistance. This review mainly focuses on the roles of emerging exosomal lncRNAs in cancer. In addition, the biogenesis of exosomes, the functions of lncRNAs, and the mechanisms of lncRNAs in exosome-mediated cell-cell communication are also summarized.

CSF extracellular vesicles and risk of disease activity after a first demyelinating event

2021 ◽  
pp. 135245852098754
Author(s):  
Gloria Dalla Costa ◽  
Tommaso Croese ◽  
Marco Pisa ◽  
Annamaria Finardi ◽  
Lorena Fabbella ◽  
...  
Keyword(s):  
Disease Activity ◽  
Extracellular Vesicles ◽  
Prognostic Markers ◽  
Cell Communication ◽  
Extracellular Vesicle ◽  
Intervention Strategies ◽  
Targeted Intervention ◽  
Improve Risk Stratification ◽  
Risk Of Disease ◽  
In Cis

Background: Extracellular vesicles (EVs), a recently described mechanism of cell communication, are released from activated microglial cells and macrophages and are a candidate biomarker in diseases characterized by chronic inflammatory process such as multiple sclerosis (MS). Methods: We explored cerebrospinal fluid extracellular vesicle (CSF EV) of myeloid origin (MEVs), cytokine and chemokine levels in patients with clinically isolated syndrome (CIS). Results: We found that CSF MEVs were significantly higher in CIS patients than in controls and were inversely correlated to CSF CCL2 levels. MEVs level were significantly associated with an shorter time to evidence of disease activity (hazard ratio: 1.01, 95% confidence interval: 1.00–1.02, p < 0.01) independently from other known prognostic markers. Conclusion: After a first demyelinating event, CSF EVs may improve risk stratification of these patients and allow more targeted intervention strategies.

scholarly journals Glycosylation of Cancer Extracellular Vesicles: Capture Strategies, Functional Roles and Potential Clinical Applications

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 109
Author(s):  
Álvaro M. Martins ◽  
Cátia C. Ramos ◽  
Daniela Freitas ◽  
Celso A. Reis
Keyword(s):  
Extracellular Vesicles ◽  
Biomarker Discovery ◽  
De Novo ◽  
Recipient Cell ◽  
Cell Communication ◽  
Cancer Biomarkers ◽  
Functional Roles ◽  
Molecular Information ◽  
Glycosylation Pathway ◽  
Organ Tropism

Glycans are major constituents of extracellular vesicles (EVs). Alterations in the glycosylation pathway are a common feature of cancer cells, which gives rise to de novo or increased synthesis of particular glycans. Therefore, glycans and glycoproteins have been widely used in the clinic as both stratification and prognosis cancer biomarkers. Interestingly, several of the known tumor-associated glycans have already been identified in cancer EVs, highlighting EV glycosylation as a potential source of circulating cancer biomarkers. These particles are crucial vehicles of cell–cell communication, being able to transfer molecular information and to modulate the recipient cell behavior. The presence of particular glycoconjugates has been described to be important for EV protein sorting, uptake and organ-tropism. Furthermore, specific EV glycans or glycoproteins have been described to be able to distinguish tumor EVs from benign EVs. In this review, the application of EV glycosylation in the development of novel EV detection and capture methodologies is discussed. In addition, we highlight the potential of EV glycosylation in the clinical setting for both cancer biomarker discovery and EV therapeutic delivery strategies.

scholarly journals The Cellular and Biological Impact of Extracellular Vesicles in Pancreatic Cancer

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 3040
Author(s):  
Zainab Hussain ◽  
Jeremy Nigri ◽  
Richard Tomasini
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Cells ◽  
Extracellular Vesicles ◽  
Cell Communication ◽  
Pancreatic Tumors ◽  
Mediated Communication ◽  
Biological Impact ◽  
Physiological Relevance ◽  
Cellular Components ◽  
Tumoral Cells

Deciphering the interactions between tumor and stromal cells is a growing field of research to improve pancreatic cancer-associated therapies and patients’ care. Indeed, while accounting for 50 to 90% of the tumor mass, many pieces of evidence reported that beyond their structural role, the non-tumoral cells composing the intra-tumoral microenvironment influence tumor cells’ proliferation, metabolism, cell death and resistance to therapies, among others. Simultaneously, tumor cells can influence non-tumoral neighboring or distant cells in order to shape a tumor-supportive and immunosuppressive environment as well as influencing the formation of metastatic niches. Among intercellular modes of communication, extracellular vesicles can simultaneously transfer the largest variety of signals and were recently reported as key effectors of cell–cell communication in pancreatic cancer, from its development to its evolution as well as its ability to resist available treatments. This review focuses on extracellular vesicles-mediated communication between different cellular components of pancreatic tumors, from the modulation of cellular activities and abilities to their biological and physiological relevance. Taking into consideration the intra-tumoral microenvironment and its extracellular-mediated crosstalk as main drivers of pancreatic cancer development should open up new therapeutic windows.

scholarly journals Extracellular Vesicles-Based Drug Delivery Systems: A New Challenge and the Exemplum of Malignant Pleural Mesothelioma

2020 ◽  
Vol 21 (15) ◽  
pp. 5432 ◽  
Author(s):  
Stefano Burgio ◽  
Leila Noori ◽  
Antonella Marino Gammazza ◽  
Claudia Campanella ◽  
Mariantonia Logozzi ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Early Diagnosis ◽  
Extracellular Vesicles ◽  
Delivery System ◽  
Malignant Pleural Mesothelioma ◽  
Cell Communication ◽  
Cell Types ◽  
Delivery Systems ◽  
Pleural Mesothelioma ◽  
Potential Use

Research for the most selective drug delivery to tumors represents a fascinating key target in science. Alongside the artificial delivery systems identified in the last decades (e.g., liposomes), a family of natural extracellular vesicles (EVs) has gained increasing focus for their potential use in delivering anticancer compounds. EVs are released by all cell types to mediate cell-to-cell communication both at the paracrine and the systemic levels, suggesting a role for them as an ideal nano-delivery system. Malignant pleural mesothelioma (MPM) stands out among currently untreatable tumors, also due to the difficulties in achieving an early diagnosis. Thus, early diagnosis and treatment of MPM are both unmet clinical needs. This review looks at indirect and direct evidence that EVs may represent both a new tool for allowing an early diagnosis of MPM and a potential new delivery system for more efficient therapeutic strategies. Since MPM is a relatively rare malignant tumor and preclinical MPM models developed to date are very few and not reliable, this review will report data obtained in other tumor types, suggesting the potential use of EVs in mesothelioma patients as well.

scholarly journals Cell-to-Cell Communication by Host-Released Extracellular Vesicles in the Gut: Implications in Health and Disease

2021 ◽  
Vol 22 (4) ◽  
pp. 2213
Author(s):  
Natalia Diaz-Garrido ◽  
Cecilia Cordero ◽  
Yenifer Olivo-Martinez ◽  
Josefa Badia ◽  
Laura Baldomà
Keyword(s):  
Extracellular Vesicles ◽  
Intestinal Mucosa ◽  
Current Knowledge ◽  
Cell Communication ◽  
Bioactive Molecules ◽  
Target Cells ◽  
Immune Functions ◽  
Intestinal Homeostasis ◽  
General Terms ◽  
Health And Disease

Communication between cells is crucial to preserve body homeostasis and health. Tightly controlled intercellular dialog is particularly relevant in the gut, where cells of the intestinal mucosa are constantly exposed to millions of microbes that have great impact on intestinal homeostasis by controlling barrier and immune functions. Recent knowledge involves extracellular vesicles (EVs) as mediators of such communication by transferring messenger bioactive molecules including proteins, lipids, and miRNAs between cells and tissues. The specific functions of EVs principally depend on the internal cargo, which upon delivery to target cells trigger signal events that modulate cellular functions. The vesicular cargo is greatly influenced by genetic, pathological, and environmental factors. This finding provides the basis for investigating potential clinical applications of EVs as therapeutic targets or diagnostic biomarkers. Here, we review current knowledge on the biogenesis and cargo composition of EVs in general terms. We then focus the attention to EVs released by cells of the intestinal mucosa and their impact on intestinal homeostasis in health and disease. We specifically highlight their role on epithelial barrier integrity, wound healing of epithelial cells, immunity, and microbiota shaping. Microbiota-derived EVs are not reviewed here.

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