scholarly journals Extracellular Vesicles in NAFLD/ALD: From Pathobiology to Therapy

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 817 ◽  
Author(s):  
Alejandra Hernández ◽  
Juan Pablo Arab ◽  
Daniela Reyes ◽  
Ainhoa Lapitz ◽  
Han Moshage ◽  
...  
Keyword(s):  
Liver Disease ◽  
Extracellular Vesicles ◽  
Liver Diseases ◽  
Experimental Studies ◽  
Cell Communication ◽  
Cell Types ◽  
Bioactive Molecules ◽  
Therapeutic Implications ◽  
Isolation And Characterization ◽  
Liver Disease Progression

In recent years, knowledge on the biology and pathobiology of extracellular vesicles (EVs) has exploded. EVs are submicron membrane-bound structures secreted from different cell types containing a wide variety of bioactive molecules (e.g., proteins, lipids, and nucleic acids (coding and non-coding RNA) and mitochondrial DNA). EVs have important functions in cell-to-cell communication and are found in a wide variety of tissues and body fluids. Better delineation of EV structures and advances in the isolation and characterization of their cargo have allowed the diagnostic and therapeutic implications of these particles to be explored. In the field of liver diseases, EVs are emerging as key players in the pathogenesis of both nonalcoholic liver disease (NAFLD) and alcoholic liver disease (ALD), the most prevalent liver diseases worldwide, and their complications, including development of hepatocellular carcinoma. In these diseases, stressed/damaged hepatocytes release large quantities of EVs that contribute to the occurrence of inflammation, fibrogenesis, and angiogenesis, which are key pathobiological processes in liver disease progression. Moreover, the specific molecular signatures of released EVs in biofluids have allowed EVs to be considered as promising candidates to serve as disease biomarkers. Additionally, different experimental studies have shown that EVs may have potential for therapeutic use as a liver-specific delivery method of different agents, taking advantage of their hepatocellular uptake through interactions with specific receptors. In this review, we focused on the most recent findings concerning the role of EVs as new structures mediating autocrine and paracrine intercellular communication in both ALD and NAFLD, as well as their potential use as biomarkers of disease severity and progression. Emerging therapeutic applications of EVs in these liver diseases were also examined, along with the potential for successful transition from bench to clinic.

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 Intestinal Permeability Is a Mechanical Rheostat in the Pathogenesis of Liver Cirrhosis

2021 ◽  
Vol 22 (13) ◽  
pp. 6921
Author(s):  
Norihisa Nishimura ◽  
Kosuke Kaji ◽  
Koh Kitagawa ◽  
Yasuhiko Sawada ◽  
Masanori Furukawa ◽  
...  
Keyword(s):  
Liver Disease ◽  
Gut Microbiota ◽  
Intestinal Permeability ◽  
Proinflammatory Cytokines ◽  
Liver Diseases ◽  
Pathogenic Bacteria ◽  
Necrosis Factor Alpha ◽  
Cytokines And Chemokines ◽  
Liver Disease Progression ◽  
Cirrhotic Patients

Recent studies have suggested that an alteration in the gut microbiota and their products, particularly endotoxins derived from Gram-negative bacteria, may play a major role in the pathogenesis of liver diseases. Gut dysbiosis caused by a high-fat diet and alcohol consumption induces increased intestinal permeability, which means higher translocation of bacteria and their products and components, including endotoxins, the so-called “leaky gut”. Clinical studies have found that plasma endotoxin levels are elevated in patients with chronic liver diseases, including alcoholic liver disease and nonalcoholic liver disease. A decrease in commensal nonpathogenic bacteria including Ruminococaceae and Lactobacillus and an overgrowth of pathogenic bacteria such as Bacteroidaceae and Enterobacteriaceae are observed in cirrhotic patients. The decreased diversity of the gut microbiota in cirrhotic patients before liver transplantation is also related to a higher incidence of post-transplant infections and cognitive impairment. The exposure to endotoxins activates macrophages via Toll-like receptor 4 (TLR4), leading to a greater production of proinflammatory cytokines and chemokines including tumor necrosis factor-alpha, interleukin (IL)-6, and IL-8, which play key roles in the progression of liver diseases. TLR4 is a major receptor activated by the binding of endotoxins in macrophages, and its downstream signal induces proinflammatory cytokines. The expression of TLR4 is also observed in nonimmune cells in the liver, such as hepatic stellate cells, which play a crucial role in the progression of liver fibrosis that develops into hepatocarcinogenesis, suggesting the importance of the interaction between endotoxemia and TLR4 signaling as a target for preventing liver disease progression. In this review, we summarize the findings for the role of gut-derived endotoxemia underlying the progression of liver pathogenesis.

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.

scholarly journals The Power of Extracellular Vesicles in Myeloproliferative Neoplasms: “Crafting” a Microenvironment That Matters

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2316
Author(s):  
Lucia Catani ◽  
Michele Cavo ◽  
Francesca Palandri
Keyword(s):  
Extracellular Vesicles ◽  
Immune Escape ◽  
Myeloproliferative Neoplasms ◽  
Cell Communication ◽  
Bioactive Molecules ◽  
Driver Genes ◽  
Hematopoietic Stem ◽  
Increased Risk ◽  
Patients Experience

Myeloproliferative Neoplasms (MPN) are acquired clonal disorders of the hematopoietic stem cells and include Essential Thrombocythemia, Polycythemia Vera and Myelofibrosis. MPN are characterized by mutations in three driver genes (JAK2, CALR and MPL) and by a state of chronic inflammation. Notably, MPN patients experience increased risk of thrombosis, disease progression, second neoplasia and evolution to acute leukemia. Extracellular vesicles (EVs) are a heterogeneous population of microparticles with a role in cell-cell communication. The EV-mediated cross-talk occurs via the trafficking of bioactive molecules such as nucleic acids, proteins, metabolites and lipids. Growing interest is focused on EVs and their potential impact on the regulation of blood cancers. Overall, EVs have been suggested to orchestrate the complex interplay between tumor cells and the microenvironment with a pivotal role in “education” and “crafting” of the microenvironment by regulating angiogenesis, coagulation, immune escape and drug resistance of tumors. This review is focused on the role of EVs in MPN. Specifically, we will provide an overview of recent findings on the involvement of EVs in MPN pathogenesis and discuss opportunities for their potential application as diagnostic and prognostic biomarkers.

scholarly journals Extracellular Vesicles and Thrombosis: Update on the Clinical and Experimental Evidence

2021 ◽  
Vol 22 (17) ◽  
pp. 9317
Author(s):  
Konstantinos Zifkos ◽  
Christophe Dubois ◽  
Katrin Schäfer
Keyword(s):  
Experimental Evidence ◽  
Extracellular Vesicles ◽  
Thrombus Formation ◽  
Experimental Studies ◽  
Cell Types ◽  
Heterogenous Group ◽  
Clearance Mechanism ◽  
And Function ◽  
Role And Function

Extracellular vesicles (EVs) compose a heterogenous group of membrane-derived particles, including exosomes, microvesicles and apoptotic bodies, which are released into the extracellular environment in response to proinflammatory or proapoptotic stimuli. From earlier studies suggesting that EV shedding constitutes a cellular clearance mechanism, it has become evident that EV formation, secretion and uptake represent important mechanisms of intercellular communication and exchange of a wide variety of molecules, with relevance in both physiological and pathological situations. The putative role of EVs in hemostasis and thrombosis is supported by clinical and experimental studies unraveling how these cell-derived structures affect clot formation (and resolution). From those studies, it has become clear that the prothrombotic effects of EVs are not restricted to the exposure of tissue factor (TF) and phosphatidylserines (PS), but also involve multiplication of procoagulant surfaces, cross-linking of different cellular players at the site of injury and transfer of activation signals to other cell types. Here, we summarize the existing and novel clinical and experimental evidence on the role and function of EVs during arterial and venous thrombus formation and how they may be used as biomarkers as well as therapeutic vectors.

scholarly journals Extracellular Vesicles: An Emerging Mechanism Governing the Secretion and Biological Roles of Tenascin-C

2021 ◽  
Vol 12 ◽  
Author(s):  
Lucas Albacete-Albacete ◽  
Miguel Sánchez-Álvarez ◽  
Miguel Angel del Pozo
Keyword(s):  
Extracellular Vesicles ◽  
Molecular Mechanisms ◽  
Cell Communication ◽  
Cell Types ◽  
Target Cells ◽  
Tenascin C ◽  
Signalling Molecules ◽  
Inflammatory Processes ◽  
Bona Fide ◽  
Cellular Components

ECM composition and architecture are tightly regulated for tissue homeostasis. Different disorders have been associated to alterations in the levels of proteins such as collagens, fibronectin (FN) or tenascin-C (TnC). TnC emerges as a key regulator of multiple inflammatory processes, both during physiological tissue repair as well as pathological conditions ranging from tumor progression to cardiovascular disease. Importantly, our current understanding as to how TnC and other non-collagen ECM components are secreted has remained elusive. Extracellular vesicles (EVs) are small membrane-bound particles released to the extracellular space by most cell types, playing a key role in cell-cell communication. A broad range of cellular components can be transported by EVs (e.g. nucleic acids, lipids, signalling molecules and proteins). These cargoes can be transferred to target cells, potentially modulating their function. Recently, several extracellular matrix (ECM) proteins have been characterized as bona fide EV cargoes, exosomal secretion being particularly critical for TnC. EV-dependent ECM secretion might underpin diseases where ECM integrity is altered, establishing novel concepts in the field such as ECM nucleation over long distances, and highlighting novel opportunities for diagnostics and therapeutic intervention. Here, we review recent findings and standing questions on the molecular mechanisms governing EV–dependent ECM secretion and its potential relevance for disease, with a focus on TnC.

scholarly journals Emerging role of extracellular vesicles in liver diseases

2019 ◽  
Vol 317 (5) ◽  
pp. G739-G749 ◽  
Author(s):  
Harmeet Malhi
Keyword(s):  
Extracellular Vesicles ◽  
Cell Communication ◽  
Cell Types ◽  
Cell Responses ◽  
Therapeutic Delivery ◽  
Disease States ◽  
Therapeutic Uses ◽  
Potential Biomarker ◽  
Secretion Pathways

Extracellular vesicles (EVs) are membrane-defined nanoparticles released by most cell types. The EVs released by cells may differ quantitatively and qualitatively from physiological states to disease states. There are several unique properties of EVs, including their proteins, lipids and nucleic acid cargoes, stability in circulation, and presence in biofluids, which make them a critical vector for cell-to-cell communication and impart utility as a biomarker. EVs may also serve as a vehicle for selective cargo secretion. Similarly, EV cargo may be selectively manipulated for targeted therapeutic delivery. In this review an overview is provided on the EV classification, biogenesis, and secretion pathways, which are conserved across cell types. Next, cargo characterization and effector cell responses are discussed in the context of nonalcoholic steatohepatitis, alcoholic hepatitis, and acetaminophen-induced liver injury. The review also discusses the potential biomarker and therapeutic uses of circulating EVs.

scholarly journals Therapeutic Potentials of Extracellular Vesicles for the Treatment of Diabetes and Diabetic Complications

2020 ◽  
Vol 21 (14) ◽  
pp. 5163 ◽  
Author(s):  
Wei Hu ◽  
Xiang Song ◽  
Haibo Yu ◽  
Jingyu Sun ◽  
Yong Zhao
Keyword(s):  
Extracellular Vesicles ◽  
Diabetic Complications ◽  
Therapeutic Potential ◽  
Cell Communication ◽  
Bioactive Molecules ◽  
Future Research ◽  
Cell Based Therapy ◽  
Liver And Kidney ◽  
Life Threatening ◽  
Treatment Of Diabetes

Extracellular vesicles (EVs), including exosomes and microvesicles, are nano-to-micrometer vesicles released from nearly all cellular types. EVs comprise a mixture of bioactive molecules (e.g., mRNAs, miRNAs, lipids, and proteins) that can be transported to the targeted cells/tissues via the blood or lymph circulation. Recently, EVs have received increased attention, owing to their emerging roles in cell-to-cell communication, or as biomarkers with the therapeutic potential to replace cell-based therapy. Diabetes comprises a group of metabolic disorders characterized by hyperglycemia that cause the development of life-threatening complications. The impacts of conventional clinical treatment are generally limited and are followed by many side effects, including hypoglycemia, obesity, and damage to the liver and kidney. Recently, several studies have shown that EVs released by stem cells and immune cells can regulate gene expression in the recipient cells, thus providing a strategy to treat diabetes and its complications. In this review, we summarize the results from currently available studies, demonstrating the therapeutic potentials of EVs in diabetes and diabetic complications. Additionally, we highlight recommendations for future research.

scholarly journals Extracellular Vesicles as Nanotherapeutics for Parkinson’s Disease

Biomolecules ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1327 ◽  
Author(s):  
Loredana Leggio ◽  
Greta Paternò ◽  
Silvia Vivarelli ◽  
Francesca L’Episcopo ◽  
Cataldo Tirolo ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Cell Communication ◽  
Bioactive Molecules ◽  
Substantia Nigra Pars Compacta ◽  
Diagnostic Tools ◽  
Target Cells ◽  
Small Interfering Rnas ◽  
Wide Range ◽  
Ligand Interactions ◽  
The Central Nervous System

Extracellular vesicles (EVs) are naturally occurring membranous structures secreted by normal and diseased cells, and carrying a wide range of bioactive molecules. In the central nervous system (CNS), EVs are important in both homeostasis and pathology. Through receptor–ligand interactions, direct fusion, or endocytosis, EVs interact with their target cells. Accumulating evidence indicates that EVs play crucial roles in the pathogenesis of many neurodegenerative disorders (NDs), including Parkinson′s disease (PD). PD is the second most common ND, characterized by the progressive loss of dopaminergic (DAergic) neurons within the Substantia Nigra pars compacta (SNpc). In PD, EVs are secreted by both neurons and glial cells, with either beneficial or detrimental effects, via a complex program of cell-to-cell communication. The functions of EVs in PD range from their etiopathogenetic relevance to their use as diagnostic tools and innovative carriers of therapeutics. Because they can cross the blood–brain barrier, EVs can be engineered to deliver bioactive molecules (e.g., small interfering RNAs, catalase) within the CNS. This review summarizes the latest findings regarding the role played by EVs in PD etiology, diagnosis, prognosis, and therapy, with a particular focus on their use as novel PD nanotherapeutics.

scholarly journals Therapeutic Potential of Extracellular Vesicles in Hypertension-Associated Kidney Disease

Hypertension ◽  
2021 ◽  
Vol 77 (1) ◽  
pp. 28-38
Author(s):  
Olga Martinez-Arroyo ◽  
Ana Ortega ◽  
Josep Redon ◽  
Raquel Cortes
Keyword(s):  
Kidney Disease ◽  
Extracellular Vesicles ◽  
Renal Damage ◽  
Therapeutic Potential ◽  
Cell Communication ◽  
Cell Types ◽  
Organ Damage ◽  
Renal Diseases ◽  
Biological Processes ◽  
Potential Use

Hypertension-mediated organ damage frequently includes renal function decline in which several mechanisms are involved. The present review outlines the state of the art on extracellular vesicles in hypertension and hypertension-related renal damage. Emerging evidence indicates that extracellular vesicles, small vesicles secreted by most cell types and body fluids, are involved in cell-to-cell communication and are key players mediating biological processes such as inflammation, endothelial dysfunction or fibrosis, mechanisms present the onset and progression of hypertension-associated kidney disease. We address the potential use of extracellular vesicles as markers of hypertension-mediated kidney damage severity and their application as therapeutic agents in hypertension-associated renal damage. The capacity of exosomes to deliver a wide variety of cargos to the target cell efficiently makes them a potential drug delivery system for treatment of renal diseases.

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