Extracellular Vesicles In Diseases Research Articles

Surface Glycan Profiling of Extracellular Vesicles by Lectin Microarray and Glycoengineering for Control of Cellular Interactions.

Extracellular vesicles (EVs)are a group of cell-derived membrane vesicles that carry a variety of cargo such as protein, nucleic acids, andlipids, and are secreted by almost all cell types. Functionally, EVs play important roles in physiological andpathological processes such as immune responses and tumor growth through intercellular communication bytransferring this molecular information between cells. Therefore, they have potential versatile clinical applicationsas disease biomarkers and drug delivery carriers. Notably, subpopulations of EVsexhibit distinct characteristics depending on their cell of origin, including the expression of surface glycans, whichhave been implicated in a variety of cellular processes such as field cancerization, cell recognition, and signaltransduction. However, these are features have not been fully exploited because of the difficulty in analyzing theseproteins. In this paper, we summarize the advancements in glycoengineering andhigh-performance lectin microarray for high-throughput analysis of EV glycans to generate an index ofheterogeneity to identify disease biomarkers, and describe how understanding the function of EVs in disease canenhance their potential application in the clinic.

The Role of Extracellular Vesicles in Diseases of the Ear, Nose, and Throat

Extracellular vesicles (EVs) are membranous nanoparticles produced by most cell types into the extracellular space and play an important role in cell-to-cell communication. Historically, EVs were categorized based on their methods of biogenesis and size into three groups: exosomes, microvesicles, and apoptotic bodies. Most recently, EV nomenclature has evolved to categorize these nanoparticles based on their size, surface markers, and/or the cell type which secreted them. Many techniques have been adopted in recent years which leverage these characteristics to isolate them from cell culture media and biological fluids. EVs carry various "cargo", including DNA, RNA, proteins, and small signaling molecules. After isolation, EVs can be characterized by various methods to analyze their unique cargo profiles which define their role in cell-to-cell communication, normal physiology, and disease progression. The study of EV cargo has become more common recently as we continue to delineate their role in various human diseases. Further understanding these mechanisms may allow for the future use of EVs as novel biomarkers and therapeutic targets in diseases. Furthermore, their unique cargo delivery mechanisms may one day be exploited to selectively deliver therapeutic agents and drugs. Despite the growing research interest in EVs, limited studies have focused on the role of EVs in the diseases of the ear, nose, and throat. In this review, we will introduce EVs and their cargo, discuss methods of isolation and characterization, and summarize the most up-to-date literature thus far into the role of EVs in diseases of the ear, nose, and throat.

Interactions between endoplasmic reticulum stress and extracellular vesicles in multiple diseases.

Immune responses can severely perturb endoplasmic reticulum (ER) function. As a protein-folding factory and dynamic calcium storage compartment, the ER plays a pivotal role in resisting pathogens and in the development of autoimmune diseases and various other diseases, including cancer, cardiovascular, neurological, orthopedic, and liver-related diseases, metabolic disorders, etc. In recent years, an increasing number of studies have shown that extracellular vesicles (EVs) play important roles in these conditions, suggesting that cells carry out some physiological functions through EVs. The formation of EVs is dependent on the ER. ER stress, as a state of protein imbalance, is both a cause and consequence of disease. ER stress promotes the transmission of pathological messages to EVs, which are delivered to target cells and lead to disease development. Moreover, EVs can transmit pathological messages to healthy cells, causing ER stress. This paper reviews the biological functions of EVs in disease, as well as the mechanisms underlying interactions between ER stress and EVs in multiple diseases. In addition, the prospects of these interactions for disease treatment are described.

Affinity-Based Enrichment of Extracellular Vesicles with Lipid Nanoprobes.

Extracellular vesicles (EVs) are lipid-bilayer-enclosed vesicles with sub-micrometer size that are released by various cells. EVs contain a tissue-specific signature wherein a variety of proteins and nucleic acids are selectively packaged. Growing evidence has shown important biological roles and clinical relevance of EVs in diseases. For EV-related studies to thrive, rapid efficient isolation of pure EVs is a prerequisite. However, lengthy procedure, low yield, low throughput, and high contaminants stemmed from existing isolation approaches hamper both basic research and large-scale clinical implementation. We have shown that lipid nanoprobes (LNP) enable spontaneous labeling and rapid isolation of EVs by coupling with magnetic enrichment. Recently, we further developed a one-step EV isolation platform that utilizes EV size-matched silica nanostructures and surface-conjugated LNPs with an integrated microfluidic mixer. EVs, derived from up to 2-ml clinical plasma, can be processed with this point-of-care device using optimized flow rate. Subsequently, contents of isolated EVs can be extracted on-chip and eluted from the device for downstream molecular analyses. The LNP-functionalized microfluidic device combined with state-of-the-art analysis platforms could have great potential in promoting EV-centered research and clinical use in the future.

Role of extracellular vesicles in disease: a novel tool for understanding disease mechanism?

Extracellular vesicles (EVs), known as exosomes and microvesicles, serve as versatile intercellular communication vehicles. EVs are membranous lipid vesicles that are released from every type of cell. It has become clear that EVs are involved in a variety of biological processes, including disease progression, and play critical roles in intracellular communication through the horizontal transfer of cellular cargoes such as proteins, DNA fragments, RNAs including mRNA and non-coding RNAs (microRNA, piRNA, and long non-coding RNA) and lipids. This exchange of information between cells has been observed in a homeostatic state and various diseases. Therefore, EVs are a promising new tool for analyzing biological networks. Furthermore, understanding EV-mediated biological networks is expected to lead to the elucidation of EV-associated pathologies and the development of EV-based therapeutics and diagnostics. In this presentation, I will introduce our recent research on the function of EVs in disease and the development of EV-targeting therapy and EV-based liquid biopsy.

Secretome of Stem Cells: Roles of Extracellular Vesicles in Diseases, Stemness, Differentiation, and Reprogramming.

Increasing evidence suggests that stem cells or stem cell-derived cells may contribute to tissue repair, not only by replacing lost tissue but also by delivering complex sets of secretory molecules, called secretomes, into host injured tissues. In recent years, extracellular vesicles (EVs) have gained much attention for their diverse and important roles in a wide range of pathophysiological processes. EVs are releasedfrom most types of cells and mediates cell-cell communication by activating receptors on target cells or by being taken up by recipient cells. EVs, including microvesicles and exosomes, encapsulate and carry proteins, nucleic acids, and lipids in the lumen and on the cell surface. Thus, EV-mediated intercellular communication has been extensively studied across various biological processes. While a number of investigations has been conducted in different tissues and body fluids, the field lacks a systematic review on stem cell-derived EVs, especially regarding their roles in stemness and differentiation. Here, we provide an overview of the pathophysiological roles of EVs and summarize recent findings focusing on EVs released from various types of stem cells. We also highlight emerging evidence for the potential implication of EVs in self-renewal, differentiation, and reprograming and discuss the benefits and limitations in translational approaches.

Identification of small compounds regulating the secretion of extracellular vesicles via a TIM4-affinity ELISA

Extracellular vesicles (EVs) are secreted from most cells and play important roles in cell–cell communication by transporting proteins, lipids, and nucleic acids. As the involvement of EVs in diseases has become apparent, druggable regulators of EV secretion are required. However, the lack of a highly sensitive EV detection system has made the development of EV regulators difficult. We developed an ELISA system using a high-affinity phosphatidylserine-binder TIM4 to capture EVs and screened a 1567-compound library. Consequently, we identified one inhibitor and three activators of EV secretion in a variety of cells. The inhibitor, apoptosis activator 2, suppressed EV secretion via a different mechanism and had a broader cellular specificity than GW4869. Moreover, the three activators, namely cucurbitacin B, gossypol, and obatoclax, had broad cellular specificity, including HEK293T cells and human mesenchymal stem cells (hMSCs). In vitro bioactivity assays revealed that some regulators control EV secretion from glioblastoma and hMSCs, which induces angiogenesis and protects cardiomyocytes against apoptosis, respectively. In conclusion, we developed a high-throughput method to detect EVs with high sensitivity and versatility, and identified four compounds that can regulate the bioactivity of EVs.

The roles of parasite-derived extracellular vesicles in disease and host-parasite communication.

In recent years, several parasites have been shown to interact with their hosts through intra- and inter-community communication mechanisms, which were identified to be mediated by extracellular vesicles (EVs) through various uptake mechanisms. EVs are a heterogenous group of nanoparticles (~30-5000nm) classified into three main types according to their size and biogenesis. EVs contain proteins, lipids, nucleic acids and metabolites from the cell of origin which are essential for genetic exchange, biomarker identification and diagnosis of pathological diseases. As important "forward lines of parasite infectivity", the parasite-secreted EVs function as information transmitters in the early-stage of host-parasite interaction and subsequent host-cell colonization. For this review, we summarize from the literature the relevance of EVs to the pathogenesis and development of human parasitic protistan diseases such as giardiasis, leishmaniasis, amoebiasis, malaria and Blastocystis-mediated gut pathology. Specific in vitro and in vivo interactions of the parasite-EVs and the host, with the reported cellular and immunological outcomes are discussed in this review. EVs have great potential to be further developed as diagnostic, immunomodulation and therapeutic alternatives to fill the knowledge gaps in the current parasitic diseases discussed in this review. Nanomedicine and vaccine development could be explored, with the utilization and/or modification of the parasitic EVs as novel treatment and prevention strategies.

Therapeutic Applications of Stem Cells and Extracellular Vesicles in Emergency Care: Futuristic Perspectives.

Regenerative medicine (RM) is an interdisciplinary field that aims to repair, replace or regenerate damaged or missing tissue or organs to function as close as possible to its physiological architecture and functions. Stem cells, which are undifferentiated cells retaining self-renewal potential, excessive proliferation and differentiation capacity into offspring or daughter cells that form different lineage cells of an organism, are considered as an important part of the RM approaches. They have been widely investigated in preclinical and clinical studies for therapeutic purposes. Extracellular vesicles (EVs) are the vital mediators that regulate the therapeutic effects of stem cells. Besides, they carry various types of cargo between cells which make them a significant contributor of intercellular communication. Given their role in physiological and pathological conditions in living cells, EVs are considered as a new therapeutic alternative solution for a variety of diseases in which there is a high unmet clinical need. This review aims to summarize and identify therapeutic potential of stem cells and EVs in diseases requiring acute emergency care such as trauma, heart diseases, stroke, acute respiratory distress syndrome and burn injury. Diseases that affect militaries or societies including acute radiation syndrome, sepsis and viral pandemics such as novel coronavirus disease 2019 are also discussed. Additionally, featuring and problematic issues that hamper clinical translation of stem cells and EVs are debated in a comparative manner with a futuristic perspective. Graphical

The Promises, Methodological Discrepancies and Pitfalls in Measurement of Cell-Derived Extracellular Vesicles in Diseases

Cell-derived extracellular vesicles (EVs) are heterogeneous population of phospholipid-based endogenously produced particles. EVs are detected in several biological fluids and tissues as biomarkers of diseases and target of medicines. The conventional approach for measuring the MPs is based on commonly used flow cytometry, fluorescent methods, and nano-particle tracking analysis that recognized as a gold standard, as well as Western blot analysis, dynamic light scattering, resistive pulse sensing, mass spectrometry-based proteomic methods and electron microscopy. However the definition of MPs using these techniques is yet under discussion. The aim of the review: to summarize the knowledge regarding detection and measurement of the EVs and define the balance between advantages and limitations of each contemporary analytical methods of EV assay.

Extracellular vesicles: biology and emerging therapeutic opportunities

Within the past decade, extracellular vesicles have emerged as important mediators of intercellular communication, being involved in the transmission of biological signals between cells in both prokaryotes and higher eukaryotes to regulate a diverse range of biological processes. In addition, pathophysiological roles for extracellular vesicles are beginning to be recognized in diseases including cancer, infectious diseases and neurodegenerative disorders, highlighting potential novel targets for therapeutic intervention. Moreover, both unmodified and engineered extracellular vesicles are likely to have applications in macromolecular drug delivery. Here, we review recent progress in understanding extracellular vesicle biology and the role of extracellular vesicles in disease, discuss emerging therapeutic opportunities and consider the associated challenges.