Role Of Extracellular Vesicles Research Articles

Possible Roles of Extracellular Vesicles in the Pathogenesis and Interventions of Immune-Mediated Central Demyelinating Diseases.

Multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) are two of the most devastating immune-mediated central demyelinating disorders. NMOSD was once considered as a variant of MS until the discovery of an antibody specific to the condition. Despite both MS and NMOSD being considered central demyelinating disorders, their pathogenesis and clinical manifestations are distinct, however the exact mechanisms associated with each disease remain unclear. Extracellular vesicles (EVs) are nano-sized vesicles originating in various cells which serve as intercellular communicators. There is a large body of evidence to show the possible roles of EVs in the pathogenesis of several diseases, including the immune-mediated central demyelinating disorders. Various types of EVs are found across disease stages and could potentially be used as a surrogate marker, as well as acting by carrying a cargo of biochemical molecules. The possibility for EVs to be used as a next-generation targeted treatment for the immune-mediated central demyelinating disorders has been investigated. The aim of this review was to comprehensively identify, compile and discuss key findings from in vitro, in vivo and clinical studies. A summary of all findings shows that: 1) the EV profiles of MS and NMOSD differ from those of healthy individuals, 2) the use of EV markers as liquid biopsy diagnostic tools appears to be promising biomarkers for both MS and NMOSD, and 3) EVs are being studied as a potential targeted therapy for MS and NMOSD. Any controversial findings are also discussed in this review.

The Role of Extracellular Vesicles in Metabolic Diseases

Extracellular vesicles represent a group of structures with the capacity to communicate with different cells and organs. This complex network of interactions can regulate multiple physiological processes in the organism. Very importantly, these processes can be altered during the appearance of different diseases including cancer, metabolic diseases, etc. In addition, these extracellular vesicles can transport different cargoes, altering the initiation of the disease, driving the progression, or even accelerating the pathogenesis. Then, we have explored the implication of these structures in different alterations such as pancreatic cancer, and in different metabolic alterations such as diabetes and its complications and non-alcoholic fatty liver disease. Finally, we have explored in more detail the communication between the liver and the pancreas. In summary, extracellular vesicles represent a very efficient system for the communication among different tissues and permit an efficient system as biomarkers of the disease, as well as being involved in the extracellular-vesicle-mediated transport of molecules, serving as a potential therapy for different diseases.

The Role of Extracellular Vesicles in the Treatment of Prostate Cancer.

Prostate cancer (PCa) has become a public health concern in elderly men due to an ever-increasing number of estimated cases. Unfortunately, the available treatments are unsatisfactory because of a lack of a durable response, especially in advanced disease states. Extracellular vesicles (EVs) are lipid-bilayer encircled nanoscale vesicles that carry numerous biomolecules (e.g., nucleic acids, proteins, and lipids), mediating the transfer of information. The past decade has witnessed a wide range of EV applications in both diagnostics and therapeutics. First, EV-based non-invasive liquid biopsies provide biomarkers in various clinical scenarios to guide treatment; EVs can facilitate the grading and staging of patients for appropriate treatment selection. Second, EVs play a pivotal role in pathophysiological processes via intercellular communication. Targeting key molecules involved in EV-mediated tumor progression (e.g., proliferation, angiogenesis, metastasis, immune escape, and drug resistance) is a potential approach for curbing PCa. Third, EVs are promising drug carriers. Naïve EVs from various sources and engineered EV-based drug delivery systems have paved the way for the development of new treatment modalities. This review discusses the recent advancements in the application of EV therapies and highlights EV-based functional materials as novel interventions for PCa.

The Role of Extracellular Vesicles in Allergic Sensitization: A Systematic Review.

Allergies affect approximately 10-30% of people worldwide, with an increasing number of cases each year; however, the underlying mechanisms are still poorly understood. In recent years, extracellular vesicles (EVs) have been suggested to play a role in allergic sensitization and skew to a T helper type 2 (Th2) response. The aim of this review is to highlight the existing evidence of EV involvement in allergies. A total of 22 studies were reviewed; 12 studies showed EVs can influence a Th2 response, while 10 studies found EVs promoted a Th1 or Treg response. EVs can drive allergic sensitization through up-regulation of pro-Th2 cytokines, such as IL-4 and IL-13. In addition, EVs from MRSA can induce IgE hypersensitivity in mice towards MRSA. On the other hand, EVs can induce tolerance in the immune system; for example, pre-exposing OVA-loaded EVs prevented OVA sensitization in mice. The current literature thus suggests that EVs play an essential role in allergy. Further research utilizing human in vitro models and clinical studies is needed to give a reliable account of the role of EVs in allergy.

Role of micro-RNAs associated with adipose-derived extracellular vesicles in metabolic disorders.

Micro-RNAs have emerged as important actors in the onset of metabolic disorders including obesity or type 2 diabetes. Particularly, several micro-RNAs are known to be key modulators of lipid metabolism, glucose homeostasis, or feeding behavior. Interestingly, the role of extracellular vesicles containing micro-RNAs, especially adipose-derived extracellular vesicles, are well-documented endocrine signals and disease biomarkers. However, the role of adipose-derived extracellular vesicles on the different tissues is different and highly related to the micro-RNA content. This review provides recent data about the potential involvement of adipose-derived extracellular vesicle-containing micro-RNAs in metabolic diseases.

The Role of Extracellular Vesicles in Efferocytosis.

Efferocytosis is the physiological process of phagocytic clearance of apoptotic cells by both professional phagocytic cells, such as macrophages, and non-professional phagocytic cells, such as epithelial cells. This process is crucial for maintaining tissue homeostasis in normal physiology. Any defects in efferocytosis can lead to pathological consequences and result in inflammatory diseases. Extracellular vesicles (EVs), including exosomes, microvesicles (MVs), and apoptotic vesicles (ApoVs), play a crucial role in proper efferocytosis. These EVs can significantly impact efferocytosis by affecting the polarization of macrophages and impacting calreticulin (CRT), TAM receptors, and MFG-E8. With further knowledge of these effects, new treatment strategies can be proposed for many inflammatory diseases caused by efferocytosis disorders. This review article aims to investigate the role of EVs during efferocytosis and its potential clinical applications in inflammatory diseases.

Role of Extracellular Vesicles (EVs) in Mediating Antioxidant Response to a Glucoraphanin Rich Meal

Aging is associated with increasing oxidative stress and declining antioxidant defences, making the body susceptible to various chronic conditions. Cruciferous vegetables contain glucoraphanin, which is metabolised into sulforaphane (SFN) in the gut(1). SFN activates a mechanism enhancing antioxidant defences that may contribute to a reduction in risk of age-related chronic diseases. Our hypothesis proposes that consuming cruciferous vegetables releases hepatic extracellular vesicles (EVs), which carry with a cargo of antioxidant proteins, into the systemic circulation(2) that are transported to ‘at risk’ tissues. We seek to characterise the antioxidant protein content of EVs from blood samples of healthy human volunteers from a prospective dietary intervention study trial called (GLOBE). The GLOBE study employs a randomised, single-blind, two-arm crossover design and involves 12 healthy male or female adults aged >55 years, at the time of enrolment, have a BMI in the range of 18.5-30 kg/m2, and have self-reported healthy (are not suffering from current illness like cancer, and gastrointestinal diseases including coeliac, Crohn’s, colitis, and irritable bowel syndrome) and not using any medications like antacids, laxatives and antibiotics which can interfere with normal digestive or metabolic processes. The dietary intervention consists of two commercially available treatments, one of which is a glucoraphanin-rich vegetable soup, while the other vegetable soup lacks glucoraphanin. Our initial focus lies in optimizing and standardizing a method for routinely characterizing EVs derived from healthy volunteers participating in dietary intervention studies. We specifically aim to extract EVs from a minimal plasma volume (2ml) using size exclusion chromatography (SEC). Subsequently, we intend to employ this method to analyse EVs obtained from 161 plasma samples collected from 12 participants during the GLOBE study for different time points like 0, 120, 240, 360, 480 min, 24 and 48 hr. Our goal is to gain insight into the role of EVs as part of the mechanisms by which consuming a moderate quantity of cruciferous vegetables may confer health benefits. Our research carries the potential to establish a standardised approach to the characterisation of EVs from healthy individuals which has several applications in nutrition research.

Role of extracellular vesicles in insulin resistance: Signaling pathways, bioactive substances, miRNAs, and therapeutic potential.

Extracellular vesicles are small lipid bilayer particles that resemble the structure of cells and range in size from 30 to 1000 nm. They transport a variety of physiologically active molecules, such as proteins, lipids, and miRNAs. Insulin resistance (IR) is a pathological disease in which insulin-responsive organs or components become less sensitive to insulin's physiological effects, resulting in decreased glucose metabolism in target organs such as the liver, muscle, and adipose tissue. Extracellular vesicles have received a lot of attention as essential intercellular communication mediators in the setting of IR. This review looks at extracellular vesicles' role in IRfrom three angles: signaling pathways, bioactive compounds, and miRNAs. Relevant publications are gathered to investigate the induction, inhibition, and bidirectional regulation of extracellular vesicles in IR, as well as their role in insulin-related illnesses. Furthermore, considering the critical function of extracellular vesicles in regulating IR, the study analyzes the practicality of employing extracellular vesicles for medication delivery and the promise of combination therapy for IR.

Роль позаклітинних везикул при фізіологічних та патологічних станах (огляд літератури)

The article presents a review of medical literature on the current views on the role of extracellular vesicle ribonucleic acid (RNA) in physiological and pathological conditions. Purpose - to highlight the current scientific knowledge about the importance of extracellular vesicles in physiological and pathological conditions, new possibilities for diagnosis and treatment. Extracellular vesicles, in particular exosomes, have experienced a revival of interest following studies indicating their importance in numerous events of intercellular interaction. The main attention is paid to the studies that investigated the pathophysiology of microvesicles and exosomes in normal and most common diseases, diagnostic features and possibilities of application in clinical practice. In the area of reproductive medicine, there is a growing interest in understanding the role of extracellular vesicles in the male and female reproductive system, as they may represent a new mechanism of communication between the reproductive tract and immature germ cells or between the mother and fetus. This could potentially have a significant impact on the understanding of pregnancy-related processes and the development of complications. Their usefulness as biomarkers of pathological conditions such as preeclampsia, spontaneous preterm labor, and polycystic ovary syndrome is being studied. Conclusions. The relationship between exosomal microRNAs and various diseases has been summarised. However, the use of exosomes has limitations due to technical and economic reasons. The purity of the isolated exosomes needs to be improved, which requires better technologies and equipment. The role of exosomal microRNAs in living organisms is highlighted, their value and potential use in terms of the source and mechanism of action of exosomes are demonstrated. More exosomal therapeutic agents will be used in future clinical trials, which gives hope for the emergence of new methods of diagnosis and treatment of many diseases. No conflict of interests was declared by the authors.

Insights into Bacterial Extracellular Vesicle Biogenesis, Functions, and Implications in Plant-Microbe Interactions.

Plant-microbe interactions play a crucial role in shaping plant health and survival. In recent years, the role of extracellular vesicles (EVs) in mediating intercellular communication between plants and microbes has emerged as an intriguing area of research. EVs serve as important carriers of bioactive molecules and genetic information, facilitating communication between cells and even between different organisms. Pathogenic bacteria leverage extracellular vesicles (EVs) to amplify their virulence, exploiting their cargo rich in toxins and virulence factors. Conversely, beneficial microbes initiate EV secretion to stimulate plant immune responses and nurture symbiotic relationships. The transfer of EV-packed small RNAs (sRNAs) has been demonstrated to facilitate the modulation of immune responses. Furthermore, harnessing the potential of EVs holds promise for the development of innovative diagnostic tools and sustainable crop protection strategies. This review highlights the biogenesis and functions of EVs in bacteria and their importance in plant defense, and paves the way for future research in this exciting field.

Communication Regarding the Myocardial Ischemia/Reperfusion and Cognitive Impairment: A Narrative Literature Review.

Coronary artery disease is a prevalent ischemic disease that results in insufficient blood supply to the heart muscle due to narrowing or occlusion of the coronary arteries. Various reperfusion strategies, including pharmacological thrombolysis and percutaneous coronary intervention, have been developed to enhance blood flow restoration. However, these interventions can lead to myocardial ischemia/reperfusion injury (MI/RI), which can cause unpredictable complications. Recent research has highlighted a compelling association between MI/RI and cognitive function, revealing pathophysiological mechanisms that may explain altered brain cognition. Manifestations in the brain following MI/RI exhibit pathological features resembling those observed in Alzheimer's disease (AD), implying a potential link between MI/RI and the development of AD. The pro-inflammatory state following MI/RI may induce neuroinflammation via systemic inflammation, while impaired cardiac function can result in cerebral under-perfusion. This review delves into the role of extracellular vesicles in transporting deleterious substances from the heart to the brain during conditions of MI/RI, potentially contributing to impaired cognition. Addressing the cognitive consequence of MI/RI, the review also emphasizes potential neuroprotective interventions and pharmacological treatments within the MI/RI model. In conclusion, the review underscores the significant impact of MI/RI on cognitive function, summarizes potential mechanisms of cardio-cerebral communication in the context of MI/RI, and offers ideas and insights for the prevention and treatment of cognitive dysfunction following MI/RI.

Extracellular Vesicles in Flaviviridae Pathogenesis: Their Roles in Viral Transmission, Immune Evasion, and Inflammation.

The members of the Flaviviridae family are becoming an emerging threat for public health, causing an increasing number of infections each year and requiring effective treatment. The consequences of these infections can be severe and include liver inflammation with subsequent carcinogenesis, endothelial damage with hemorrhage, neuroinflammation, and, in some cases, death. The mechanisms of Flaviviridae pathogenesis are being actively investigated, but there are still many gaps in their understanding. Extracellular vesicles may play important roles in these mechanisms, and, therefore, this topic deserves detailed research. Recent data have revealed the involvement of extracellular vesicles in steps of Flaviviridae pathogenesis such as transmission, immune evasion, and inflammation, which is critical for disease establishment. This review covers recent papers on the roles of extracellular vesicles in the pathogenesis of Flaviviridae and includes examples of clinical applications of the accumulated data.

Extracellular vesicles in parasitic diseases – from pathogenesis to future diagnostic tools

Parasitic diseases are still a major public health problem especially among individuals of low socioeconomic status in underdeveloped countries. In recent years it has been demonstrated that parasites can release extracellular vesicles that participate in the host-parasite communication, immune evasion, and in governing processes associated with host infection. Extracellular vesicles are membrane-bound structures released into the extracellular space that can carry several types of biomolecules, including proteins, lipids, nucleic acids, and metabolites, which directly impact the target cells. Extracellular vesicles have attracted wide attention due to their relevance in host-parasite communication and for their potential value in applications such as in the diagnostic biomarker discovery. This review of the literature aimed to join the current knowledge on the role of extracellular vesicles in host-parasite interaction and summarize its molecular content, providing information for the acquisition of new tools that can be used in the diagnosis of parasitic diseases. These findings shed light to the potential of extracellular vesicle cargo derived from protozoa parasites as novel diagnostic tools.

The Role of Extracellular Vesicles in SARS-CoV-2-Induced Acute Kidney Injury: An Overview.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected millions worldwide since its outbreak in the winter of 2019. While extensive research has primarily focused on the deleterious respiratory effects of SARS-CoV-2 in recent years, its pan-tropism has become evident. Among the vital organs susceptible to SARS-CoV-2 infection is the kidney. Post SARS-CoV-2 infection, patients have developed coronavirus disease 19 (COVID-19), with reported incidences of COVID-19 patients developing acute kidney injury (AKI). Given COVID-19's multisystemic manifestation, our review focuses on the impact of SARS-CoV-2 infection within the renal system with an emphasis on the current hypotheses regarding the role of extracellular vesicles (EVs) in SARS-CoV-2 pathogenesis. Emerging studies have shown that SARS-CoV-2 can directly infect the kidney, whereas EVs are involved in the spreading of SARS-CoV-2 particles to other neighboring cells. Once the viral particles are within the kidney system, many proinflammatory signaling pathways are shown to be activated, resulting in AKI. Hence, clinical investigation of urinary proinflammatory components and total urinary extracellular vesicles (uEVs) with viral particles have been used to assess the severity of AKI in patients with COVID-19. Remarkedly, new emerging studies have shown the potential of mesenchymal stem cell-derived EVs (MSC-EVs) and ACE2-containing EVs as a hopeful therapeutic tool to inhibit SARS-CoV-2 RNA replication and block viral entry, respectively. Overall, understanding EVs' physiological role is crucial and hopefully will rejuvenate our therapeutic approach towards COVID-19 patients with AKI.

The role of extracellular vesicles in cholangiocarcinoma tumor microenvironment.

Cholangiocarcinoma (CCA) is a highly aggressive malignant tumor that originates from the biliary system. With restricted treatment options at hand, the challenging aspect of early CCA diagnosis leads to a bleak prognosis. Besides the intrinsic characteristics of tumor cells, the generation and progression of CCA are profoundly influenced by the tumor microenvironment, which engages in intricate interactions with cholangiocarcinoma cells. Of notable significance is the role of extracellular vesicles as key carriers in enabling communication between cancer cells and the tumor microenvironment. This review aims to provide a comprehensive overview of current research examining the interplay between extracellular vesicles and the tumor microenvironment in the context of CCA. Specifically, we will emphasize the significant contributions of extracellular vesicles in molding the CCA microenvironment and explore their potential applications in the diagnosis, prognosis assessment, and therapeutic strategies for this aggressive malignancy.

Applications of emerging extracellular vesicles technologies in the treatment of inflammatory diseases.

The emerging extracellular vesicles technologies is an advanced therapeutic approach showing promising potential for addressing inflammatory diseases. These techniques have been proven to have positive effects on immune modulation and anti-inflammatory responses. With these advancements, a comprehensive review and update on the role of extracellular vesicles in inflammatory diseases have become timely. This review aims to summarize the research progress of extracellular vesicle technologies such as plant-derived extracellular vesicles, milk-derived extracellular vesicles, mesenchymal stem cell-derived extracellular vesicles, macrophage-derived extracellular vesicles, etc., in the treatment of inflammatory diseases. It elucidates their potential significance in regulating inflammation, promoting tissue repair, and treating diseases. The goal is to provide insights for future research in this field, fostering the application and development of extracellular vesicle technology in the treatment of inflammatory diseases.

Pathogenic and therapeutic role of exosomes in neurodegenerative disorders.

Neurodegenerative disorders affect millions of people worldwide, and the prevalence of these disorders is only projected to rise as the number of people over 65 will drastically increase in the coming years. While therapies exist to aid in symptomatic relief, effective treatments that can stop or reverse the progress of each neurodegenerative disease are lacking. Recently, research on the role of extracellular vesicles as disease markers and therapeutics has been intensively studied. Exosomes, 30-150 nm in diameter, are one type of extracellular vesicles facilitating cell-to-cell communication. Exosomes are thought to play a role in disease propagation in a variety of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Accordingly, the exosomes derived from the patients are an invaluable source of disease biomarkers. On the other hand, exosomes, especially those derived from stem cells, could serve as a therapeutic for these disorders, as seen by a rapid increase in clinical trials investigating the therapeutic efficacy of exosomes in different neurological diseases. This review summarizes the pathological burden and therapeutic approach of exosomes in neurodegenerative disorders. We also highlight how heat shock increases the yield of exosomes while still maintaining their therapeutic efficacy. Finally, this review concludes with outstanding questions that remain to be addressed in exosomal research.

CSF Extracellular Vesicle Aβ42 and Tau/Aβ42 Ratio Are Associated with Cognitive Impairment in Older People with HIV.

HIV-associated neurocognitive disorders (HAND) remain prevalent despite viral suppression on antiretroviral therapy (ART). Older people with HIV (PWH) are also at risk for amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD). β-amyloid (Aβ) and Tau biomarkers are associated with aMCI/AD, but their relationship to HAND is unclear. Given the role of extracellular vesicles (EVs) in age-related neurological disorders, we investigated soluble and EV-associated Aβ42, total Tau, NFL, GFAP, ICAM-1, VCAM-1, and CRP in relation to cognitive impairment in PWH. Plasma and CSF EVs were isolated from 184 participants (98 PWH on ART and 86 HIV- controls). Biomarkers were measured using Meso Scale Discovery assays. The median age of PWH was 53 years, and 52% were diagnosed with mild forms of HAND. PWH had increased plasma NFL (p = 0.04) and CSF Aβ42 (p = 0.0003) compared with HIV- controls but no significant difference in Tau or EV-associated forms of these markers. CSF EV Aβ42 was decreased (p = 0.0002) and CSF EV Tau/Aβ42 ratio was increased (p = 0.001) in PWH with HAND vs. no HAND, while soluble forms of these markers showed no significant differences. Decreased CSF EV Aβ42 (p < 0.0001) and an increased CSF EV Tau/Aβ42 ratio (p = 0.0003) were associated with lower neurocognitive T scores in age-adjusted models; an optimal model included both CSF EV Aβ42 and plasma NFL. Levels of soluble, but not EV-associated, ICAM-1, VCAM-1, and CRP were increased in PWH with HAND vs. no HAND (p < 0.05). These findings suggest that decreased Aβ42 and an increased Tau/Aβ42 ratio in CSF EVs are associated with cognitive impairment in older PWH, and these EV-associated biomarkers may help to distinguish aMCI/AD from HIV-related cognitive disorders in future studies.

Resistin Induces Migration and Invasion in PC3 Prostate Cancer Cells: Role of Extracellular Vesicles.

Resistin is an adipokine with metabolic and inflammatory functions. Epidemiological and translational studies report that an increase in plasma levels and tissue expression of resistin increases the aggressiveness of prostate tumor cells. Extracellular vesicles (EVs) are secreted constitutively and induced by cytokines, growth factors, and calcium and are found in multiple biological fluids such as saliva, serum, semen, and urine. In particular, EVs have been shown to promote tumor progression through the induction of proliferation, growth, angiogenesis, resistance to chemotherapy, and metastasis. However, the role of resistin in the migration, invasion, and secretion of EVs in invasive prostate tumor cells remains to be studied. In the present study, we demonstrate that resistin induces increased migration and invasion in PC3 cells. In addition, these phenomena are accompanied by increased p-FAK levels and increased secretion of MMP-2 and MMP-9 in resistin-treated PC3 cells. Interestingly, EVs isolated from supernatants of PC3 cells treated with resistin induce an increase in migration and invasion accompanied by high MMP-2 and MMP-9 secretion in an autocrine stimulation model. In summary, our data for the first time demonstrate that resistin induces migration and invasion, partly through the secretion of EVs with pro-invasive characteristics in PC3 cells.

Pulsed ultrasound promotes secretion of anti-inflammatory extracellular vesicles from skeletal myotubes via elevation of intracellular calcium level.

The regulation of inflammatory responses is an important intervention in biological function and macrophages play an essential role during inflammation. Skeletal muscle is the largest organ in the human body and releases various factors which mediate anti-inflammatory/immune modulatory effects. Recently, the roles of extracellular vesicles (EVs) from a large variety of cells are reported. In particular, EVs released from skeletal muscle are attracting attention due to their therapeutic effects on dysfunctional organs and tissues. Also, ultrasound (US) promotes release of EVs from skeletal muscle. In this study, we investigated the output parameters and mechanisms of US-induced EV release enhancement and the potential of US-treated skeletal muscle-derived EVs in the regulation of inflammatory responses in macrophages. High-intensity US (3.0 W/cm2) irradiation increased EV secretion from C2C12 murine muscle cells via elevating intracellular Ca2+ level without negative effects. Moreover, US-induced EVs suppressed expression levels of pro-inflammatory factors in macrophages. miRNA sequencing analysis revealed that miR-206-3p and miR-378a-3p were especially abundant in skeletal myotube-derived EVs. In this study we demonstrated that high-intensity US promotes the release of anti-inflammatory EVs from skeletal myotubes and exert anti-inflammatory effects on macrophages.