Extracellular vesicles as biomarkers for diagnostic and prognostic application in cardiovascular disease

2020 ◽  
Vol 2 (1) ◽  
pp. 36-41
Author(s):  
Christoph Lipps
Keyword(s):  
Cardiovascular Disease ◽  
Extracellular Vesicles ◽  
Diagnostic And Prognostic Application ◽  
Cell Communication ◽  
Current Evidence ◽  
Cellular Origin ◽  
New Class ◽  
Diagnosis And Prognosis ◽  
Prognostic Application ◽  
Pulmonary Arterial

Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality worldwide. Early diagnosis and the development of a prognosis is important for management or secondary prevention of the disease. In the past few decades, various biomarkers have been identified for improved risk assessment, more accurate diagnosis and prognosis, and a better understanding of the underlying pathophysiology in CVD. Extracellular vesicles (EVs) are thought to be important to cell-to-cell communication in the heart, and EV counts, cellular origin, and EV content have been related to CVD. This review examines current evidence for the potential application of EVs as a new class of biomarkers in CVD. Keywords: extracellular vesicles, biomarker, liquid biopsy, cardiovascular disease, myocardial infarction, heart failure, pulmonary arterial hypertension

scholarly journals Extracellular Vesicles from the Protozoa Acanthamoeba castellanii: Their Role in Pathogenesis, Environmental Adaptation and Potential Applications

2019 ◽  
Vol 6 (1) ◽  
pp. 13 ◽  
Author(s):  
Diego Gonçalves ◽  
Marina Ferreira ◽  
Allan Guimarães
Keyword(s):  
Extracellular Vesicles ◽  
Cell Communication ◽  
Acanthamoeba Castellanii ◽  
Living Organism ◽  
Biofuel Production ◽  
Cellular Origin ◽  
Wide Range ◽  
Free Living Amoeba ◽  
Potential Applications ◽  
Multicellular Organisms

Extracellular vesicles (EVs) are membranous compartments of distinct cellular origin and biogenesis, displaying different sizes and include exosomes, microvesicles, and apoptotic bodies. The EVs have been described in almost every living organism, from simple unicellular to higher evolutionary scale multicellular organisms, such as mammals. Several functions have been attributed to these structures, including roles in energy acquisition, cell-to-cell communication, gene expression modulation and pathogenesis. In this review, we described several aspects of the recently characterized EVs of the protozoa Acanthamoeba castellanii, a free-living amoeba (FLA) of emerging epidemiological importance, and compare their features to other parasites’ EVs. These A. castellanii EVs are comprised of small microvesicles and exosomes and carry a wide range of molecules involved in many biological processes like cell signaling, carbohydrate metabolism and proteolytic activity, such as kinases, glucanases, and proteases, respectively. Several biomedical applications of these EVs have been proposed lately, including their use in vaccination, biofuel production, and the pharmaceutical industry, such as platforms for drug delivery.

scholarly journals Extracellular Vesicles in the Blood of Dogs with Cancer—A Preliminary Study

Animals ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. 575 ◽  
Author(s):  
Magdalena Żmigrodzka ◽  
Olga Witkowska-Piłaszewicz ◽  
Alicja Rzepecka ◽  
Anna Cywińska ◽  
Dariusz Jagielski ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Cell Communication ◽  
Biological Marker ◽  
Annexin V ◽  
Absolute Number ◽  
Cellular Origin ◽  
Healthy Dogs ◽  
Preliminary Study ◽  
Cellular Markers ◽  
Abundant Population

Extracellular vesicles (EVs) are a heterogeneous population of submicron-sized structures released during the activation, proliferation, or apoptosis of various types of cells. Due to their size, their role in cell-to-cell communication in cancer is currently being discussed. In blood, the most abundant population of EVs is platelet-derived EVs (PEVs). The aim of this study was to estimate the absolute number and the origin of EVs in the blood of healthy dogs and of dogs with various types of cancer. The EV absolute number and cellular origin were examined by flow cytometry technique. EVs were classified on the basis of surface annexin V expression (phosphatidylserine PS+) and co-expression of specific cellular markers (CD61, CD45, CD3, CD21). The number of PEVs was significantly higher in dogs with cancer (median: 409/µL, range: 42–2748/µL vs. median: 170/µL, range: 101–449/µL in controls). The numbers of EVs derived from leukocytes (control median: 86/µL, range: 40–240/µL; cancer median: 443/µL, range: 44–3 352/µL) and T cells (control median: 5/µL, range: 2–66/µL; cancer median: 108/µL, range: 3–1735/µL) were higher in dogs with neoplasia compared to healthy controls. The estimation of PEV and leukocyte-derived EV counts may provide a useful biological marker in dogs with cancer.

scholarly journals Optimized Protocol for Isolation of Small Extracellular Vesicles from Human and Murine Lymphoid Tissues

2020 ◽  
Vol 21 (15) ◽  
pp. 5586 ◽  
Author(s):  
Marie Bordas ◽  
Géraldine Genard ◽  
Sibylle Ohl ◽  
Michelle Nessling ◽  
Karsten Richter ◽  
...  
Keyword(s):  
Size Exclusion Chromatography ◽  
Extracellular Vesicles ◽  
Cell Communication ◽  
Size Exclusion ◽  
Lymphoid Tissues ◽  
Premetastatic Niche ◽  
Diagnosis And Prognosis ◽  
Isolation And Characterization ◽  
Optimized Protocol ◽  
Exclusion Chromatography

Small extracellular vesicles (sEVs) are nanoparticles responsible for cell-to-cell communication released by healthy and cancer cells. Different roles have been described for sEVs in physiological and pathological contexts, including acceleration of tissue regeneration, modulation of tumor microenvironment, or premetastatic niche formation, and they are discussed as promising biomarkers for diagnosis and prognosis in body fluids. Although efforts have been made to standardize techniques for isolation and characterization of sEVs, current protocols often result in co-isolation of soluble protein or lipid complexes and of other extracellular vesicles. The risk of contaminated preparations is particularly high when isolating sEVs from tissues. As a consequence, the interpretation of data aiming at understanding the functional role of sEVs remains challenging and inconsistent. Here, we report an optimized protocol for isolation of sEVs from human and murine lymphoid tissues. sEVs from freshly resected human lymph nodes and murine spleens were isolated comparing two different approaches—(1) ultracentrifugation on a sucrose density cushion and (2) combined ultracentrifugation with size-exclusion chromatography. The purity of sEV preparations was analyzed using state-of-the-art techniques, including immunoblots, nanoparticle tracking analysis, and electron microscopy. Our results clearly demonstrate the superiority of size-exclusion chromatography, which resulted in a higher yield and purity of sEVs, and we show that their functionality alters significantly between the two isolation protocols.

scholarly journals BIRC7 and STC2 expression are associated with tumorigenesis and poor outcome in extrahepatic cholangiocarcinoma

2020 ◽  
Author(s):  
Jiequn Li ◽  
Zhulin Yang ◽  
Shengfu Huang ◽  
Daiqiang Li
Keyword(s):  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Diagnostic And Prognostic Application ◽  
Staining Technique ◽  
Clinicopathological Characteristics ◽  
Extrahepatic Cholangiocarcinoma ◽  
Node Metastasis ◽  
Diagnosis And Prognosis ◽  
Potential Biomarker ◽  
Prognostic Application

Abstract Background: Extrahepatic cholangiocarcinoma (EHCC) is a highly aggressive epithelial malignancy and has a poor prognosis for the insensitivity to therapies and difficulty in detection. Novel targets and biomarkers are urgently needed to develop for functional, diagnostic and prognostic application on EHCC.Methods: Immunohistochemical staining technique using the EnVision antibody complex was performed on the samples obtained from 100 EHCC，30 peritumoral extrahepatic biliary tract (EHBT), 10 EHBT adenomas and 15 normal EHBT tissues.Results: The positive rates of BIRC7 and STC2 expression in tissues obtained from peritumoral EHBT, EHBT adenomas and normal EHBT were significantly lower than those in EHCC tissues. BIRC7 and STC2 proteins were expressed at significantly higher levels in patients with lymph node metastasis, invasion of adjacent tissues, and higher TNM stage (III and/or IV) and unable to undergo resection (biopsy only). Kaplan-Meier survival curves indicated that significantly decreased overall survival rate in patients with positive-BIRC7 or positive-STC2 expression compared with patients of negative-BIRC7 or negative-STC2 expression, respectively. Cox-proportional regression analysis demonstrated that positive-BIRC7 and positive-STC2 expression, along with poor differentiation of EHCC, tumor size >3cm, lymph node metastasis, invasion of adjacent tissues and unable to undergo resection are independent prognostic factors of EHCC patients.Conclusions：The levels of BIRC7 and STC2 expression were correlated with clinicopathological characteristics of EHCC, and positive expression of BIRC7 and STC2 are associated with progression and poor clinical outcomes of EHCC. BIRC7 and STC2 might be a potential biomarker for EHCC diagnosis and prognosis.

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>

The Use of Mesenchymal Stem Cells and their Derived Extracellular Vesicles in Cardiovascular Disease Treatment

2020 ◽  
Vol 15 (7) ◽  
pp. 623-638
Author(s):  
Saeideh Gholamzadeh Khoei ◽  
Fateme Karimi Dermani ◽  
Sara Malih ◽  
Nashmin Fayazi ◽  
Mohsen Sheykhhasan
Keyword(s):  
Cardiovascular Disease ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Extracellular Vesicles ◽  
Adult Stem Cells ◽  
Heart Diseases ◽  
Therapeutic Option ◽  
Current Treatment ◽  
Treatment Modalities ◽  
Cellular Source

Background: Cardiovascular disease (CVD), including disorders of cardiac muscle and vascular, is the major cause of death globally. Many unsuccessful attempts have been made to intervene in the disease's pathogenesis and treatment. Stem cell-based therapies, as a regeneration strategy, cast a new hope for CVD treatment. One of the most well-known stem cells is mesenchymal stem cells (MSCs), classified as one of the adult stem cells and can be obtained from different tissues. These cells have superior properties, such as proliferation and highly specialized differentiation. On the other hand, they have the potential to modulate the immune system and anti-inflammatory activity. One of their most important features is the secreting the extracellular vesicles (EVs) like exosomes (EXOs) as an intercellular communication system mediating the different physiological and pathophysiological affairs. Methods: In this review study, the importance of MSC and its secretory exosomes for the treatment of heart disease has been together and specifically addressed and the use of these promising natural and accessible agents is predicted to replace the current treatment modalities even faster than we imagine. Results: MSC derived EXOs by providing a pro-regenerative condition allowing innate stem cells to repair damaged tissues successfully. As a result, MSCs are considered as the appropriate cellular source in regenerative medicine. In the plethora of experiments, MSCs and MSC-EXOs have been used for the treatment and regeneration of heart diseases and myocardial lesions. Conclusions: Administration of MSCs has been provided a replacement therapeutic option for heart regeneration, obtaining great attention among the basic researcher and the medical doctors.

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.

Salivary biomarkers in cardiovascular disease: An insight into the current evidence

FEBS Journal ◽  
2020 ◽  
Author(s):  
Eshak I. Bahbah ◽  
Christa Noehammer ◽  
Walter Pulverer ◽  
Martin Jung ◽  
Andreas Weinhäusel
Keyword(s):  
Cardiovascular Disease ◽  
Current Evidence ◽  
Salivary Biomarkers ◽  
Insight Into

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.

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