scholarly journals Extracellular Vesicles Physiological Role and the Particular Case of Disease-Spreading Mechanisms in Polyglutamine Diseases

2021 ◽  
Vol 22 (22) ◽  
pp. 12288
Author(s):  
Ricardo Moreira ◽  
Liliana S. Mendonça ◽  
Luís Pereira de Almeida
Keyword(s):  
Extracellular Vesicles ◽  
Focal Point ◽  
Cell Communication ◽  
Physiological Role ◽  
Brain Regions ◽  
Misfolded Proteins ◽  
Polyglutamine Diseases ◽  
Therapeutic Approaches ◽  
Disease Spreading ◽  
Toxic Components

Recent research demonstrated pathological spreading of the disease-causing proteins from one focal point across other brain regions for some neurodegenerative diseases, such as Parkinson’s and Alzheimer’s disease. Spreading mediated by extracellular vesicles is one of the proposed disease-spreading mechanisms. Extracellular vesicles are cell membrane-derived vesicles, used by cells for cell-to-cell communication and excretion of toxic components. Importantly, extracellular vesicles carrying pathological molecules, when internalized by “healthy” cells, may trigger pathological pathways and, consequently, promote disease spreading to neighboring cells. Polyglutamine diseases are a group of genetic neurodegenerative disorders characterized by the accumulation of mutant misfolded proteins carrying an expanded tract of glutamines, including Huntington’s and Machado–Joseph disease. The pathological spread of the misfolded proteins or the corresponding mutant mRNA has been explored. The understanding of the disease-spreading mechanism that plays a key role in the pathology progression of these diseases can result in the development of effective therapeutic approaches to stop disease progression, arresting the spread of the toxic components and disease aggravation. Therefore, the present review’s main focus is the disease-spreading mechanisms with emphasis on polyglutamine diseases and the putative role played by extracellular vesicles in this process.

scholarly journals Extracellular Vesicles, Influential Players of Intercellular Communication within Adult Neurogenic Niches

2020 ◽  
Vol 21 (22) ◽  
pp. 8819
Author(s):  
Morris Losurdo ◽  
Mariagrazia Grilli
Keyword(s):  
Extracellular Vesicles ◽  
Current Knowledge ◽  
Ventricular Zone ◽  
Critical Role ◽  
Cell Communication ◽  
Physiological Role ◽  
Cell Types ◽  
Brain Regions ◽  
Adult Brain ◽  
Biologically Active

Adult neurogenesis, involving the generation of functional neurons from adult neural stem cells (NSCs), occurs constitutively in discrete brain regions such as hippocampus, sub-ventricular zone (SVZ) and hypothalamus. The intrinsic structural plasticity of the neurogenic process allows the adult brain to face the continuously changing external and internal environment and requires coordinated interplay between all cell types within the specialized microenvironment of the neurogenic niche. NSC-, neuronal- and glia-derived factors, originating locally, regulate the balance between quiescence and self-renewal of NSC, their differentiation programs and the survival and integration of newborn cells. Extracellular Vesicles (EVs) are emerging as important mediators of cell-to-cell communication, representing an efficient way to transfer the biologically active cargos (nucleic acids, proteins, lipids) by which they modulate the function of the recipient cells. Current knowledge of the physiological role of EVs within adult neurogenic niches is rather limited. In this review, we will summarize and discuss EV-based cross-talk within adult neurogenic niches and postulate how EVs might play a critical role in the regulation of the neurogenic process.

scholarly journals Wharton’s Jelly Mesenchymal Stromal Cells and Derived Extracellular Vesicles as Post-Myocardial Infarction Therapeutic Toolkit: An Experienced View

Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1336
Author(s):  
Noelia Muñoz-Domínguez ◽  
Santiago Roura ◽  
Cristina Prat-Vidal ◽  
Joaquim Vives
Keyword(s):  
Myocardial Infarction ◽  
Extracellular Vesicles ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Cell Communication ◽  
Multipotent Mesenchymal Stromal Cells ◽  
Wharton’S Jelly ◽  
Therapeutic Approaches ◽  
Wharton's Jelly ◽  
Evidence Based Therapy

Outstanding progress has been achieved in developing therapeutic options for reasonably alleviating symptoms and prolonging the lifespan of patients suffering from myocardial infarction (MI). Current treatments, however, only partially address the functional recovery of post-infarcted myocardium, which is in fact the major goal for effective primary care. In this context, we largely investigated novel cell and TE tissue engineering therapeutic approaches for cardiac repair, particularly using multipotent mesenchymal stromal cells (MSC) and natural extracellular matrices, from pre-clinical studies to clinical application. A further step in this field is offered by MSC-derived extracellular vesicles (EV), which are naturally released nanosized lipid bilayer-delimited particles with a key role in cell-to-cell communication. Herein, in this review, we further describe and discuss the rationale, outcomes and challenges of our evidence-based therapy approaches using Wharton’s jelly MSC and derived EV in post-MI management.

scholarly journals Origins to Outcomes: A Role for Extracellular Vesicles in Precision Medicine

2018 ◽  
Vol 1 (1) ◽  
pp. 18-42 ◽  
Author(s):  
John Savage ◽  
Ciaran Manus Maguire ◽  
Adrielle Prina-Mello
Keyword(s):  
Precision Medicine ◽  
Extracellular Vesicles ◽  
Cell Communication ◽  
Cell Types ◽  
Disease Diagnosis ◽  
Biological Research ◽  
Biological Processes ◽  
Therapeutic Approaches ◽  
Recent Developments ◽  
Almost All

Extracellular vesicles (EVs) are of great interest in biological research, and though they are a relatively recent discovery, they have rapidly shown great potential for use in clinical applications. The various techniques used in EV isolation along with their respective strengths, weaknesses, and potential for downstream applications are outlined here. A brief description of the different approaches in exosome characterisation are subsequently described. It has been highlighted that despite the recent developments in these processes, there is still a great deal of refinement to be made. EVs are produced by almost all cell types, found in many biological samples, and are implicated in multiple biological processes including cargo trafficking, cell-cell communication, and signal transduction. The presence of these EVs and their varied cargo in a biological sample can be indicative in disease diagnosis, and guide precision medicine-based approaches to disease management. EVs have been reported to actin the benefit of the cell through moderating repair and regeneration, but they can also act to the detriment of the cell through increased tumorigenesis and metastasis. This duality is intriguing as it can allow for the use of EVs in distinct therapeuticapproaches and displays their versatility in potential downstream applications. In this review, examples of the cellular roles of EVs and their applications in pathological and regenerative contexts are explored. In reviewing some of the developments madein recent times, EVs are shown to be very promising both in diagnostic and therapeutic approaches.

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>

Peptide-Based Therapeutic Approaches for Treatment of the Polyglutamine Diseases

2014 ◽  
Vol 21 (23) ◽  
pp. 2575-2582 ◽  
Author(s):  
Toshihide Takeuchi ◽  
H. Popiel ◽  
Shiroh Futaki ◽  
Keiji Wada ◽  
Yoshitaka Nagai
Keyword(s):  
Polyglutamine Diseases ◽  
Therapeutic Approaches

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.

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