Extracellular vesicles as gold mine for new diagnostic and therapeutic approaches in medicine

2019 ◽  
Vol 1 (1) ◽  
pp. 10-17
Author(s):  
Stefan Holdenrieder
Keyword(s):  
Extracellular Vesicles ◽  
Intercellular Communication ◽  
Specific Information ◽  
Clinical Validation ◽  
Gold Mine ◽  
Therapeutic Approaches ◽  
Bodily Fluids ◽  
Therapeutic Drugs ◽  
Physiological Processes ◽  
Cells Of Origin

Extracellular vesicles (EVs) are a heterogeneous group of subcellular particles shed from cells of origin by diverse mechanisms. They carry specific information and are responsible for efficient intercellular communication that is highly important in many physiological processes as well as for the pathogenesis and progression of several diseases. Their unique properties offer the opportunity to use them also for the delivery of therapeutic drugs. When released into the blood or other bodily fluids they serve as sensitive liquid profiling biomarkers in many dispositions. For future use in diagnostic settings, further efforts are required for better standardization of the methods as well as the analytical, pre-analytical and clinical validation of the markers.

scholarly journals Extracellular Vesicles: New Endogenous Shuttles for miRNAs in Cancer Diagnosis and Therapy?

2020 ◽  
Vol 21 (18) ◽  
pp. 6486 ◽  
Author(s):  
Stefano Martellucci ◽  
Nicola Salvatore Orefice ◽  
Adriano Angelucci ◽  
Amalia Luce ◽  
Michele Caraglia ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Intercellular Communication ◽  
Stromal Cells ◽  
Clinical Utility ◽  
Current Knowledge ◽  
Human Cancer ◽  
Heterogeneous Population ◽  
Bodily Fluids ◽  
Cancer Diagnosis And Therapy

Extracellular Vesicles (EVs) represent a heterogeneous population of membranous cell-derived structures, including cargo-oriented exosomes and microvesicles. EVs are functionally associated with intercellular communication and play an essential role in multiple physiopathological conditions. Shedding of EVs is frequently increased in malignancies and their content, including proteins and nucleic acids, altered during carcinogenesis and cancer progression. EVs-mediated intercellular communication between tumor cells and between tumor and stromal cells can modulate, through cargo miRNA, the survival, progression, and drug resistance in cancer conditions. These consolidated suggestions and EVs’ stability in bodily fluids have led to extensive investigations on the potential employment of circulating EVs-derived miRNAs as tumor biomarkers and potential therapeutic vehicles. In this review, we highlight the current knowledge about circulating EVs-miRNAs in human cancer and the application limits of these tools, discussing their clinical utility and challenges in functions such as in biomarkers and instruments for diagnosis, prognosis, and therapy.

scholarly journals Extracellular Vesicles in Viral Pathogenesis: A Case of Dr. Jekyll and Mr. Hyde

Life ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 45
Author(s):  
Lada Purvinsh ◽  
Andrey Gorshkov ◽  
Aleksandra Brodskaia ◽  
Andrey Vasin
Keyword(s):  
Extracellular Vesicles ◽  
Protective Factor ◽  
Fundamental Property ◽  
Molecular Composition ◽  
Biologically Active ◽  
Therapeutic Approaches ◽  
New Therapeutic Approaches ◽  
Physiological Processes ◽  
Infected Cells

Secretion of extracellular vesicles (EVs) is a fundamental property of living cells. EVs are known to transfer biological signals between cells and thus regulate the functional state of recipient cells. Such vesicles mediate the intercellular transport of many biologically active molecules (proteins, nucleic acids, specific lipids) and participate in regulation of key physiological processes. In addition, EVs are involved in the pathogenesis of multiple diseases: infectious, neurodegenerative, and oncological. The current EV classification into microvesicles, apoptotic bodies, and exosomes is based on their size, pathways of cellular biogenesis, and molecular composition. This review is focused on analysis of the role of EVs (mainly exosomes) in the pathogenesis of viral infection. We briefly characterize the biogenesis and molecular composition of various EV types. Then, we consider EV-mediated pro- and anti-viral mechanisms. EV secretion by infected cells can be an important factor of virus spread in target cell populations, or a protective factor limiting viral invasion. The data discussed in this review, on the effect of EV secretion by infected cells on processes in neighboring cells and on immune cells, are of high significance in the search for new therapeutic approaches and for design of new generations of vaccines.

scholarly journals Circular RNAs: Potential Applications as Therapeutic Targets and Biomarkers in Breast Cancer

2021 ◽  
Vol 7 (1) ◽  
pp. 2
Author(s):  
Debina Sarkar ◽  
Sarah D. Diermeier
Keyword(s):  
Breast Cancer ◽  
Translational Regulation ◽  
Closed Loop ◽  
Mechanisms Of Action ◽  
Circular Rnas ◽  
Therapeutic Approaches ◽  
Mirna Sponge ◽  
Bodily Fluids ◽  
Potential Applications ◽  
Non Coding Rnas

Circular RNAs (circRNAs) are a class of non-coding RNAs that form a covalently closed loop. A number of functions and mechanisms of action for circRNAs have been reported, including as miRNA sponge, exerting transcriptional and translational regulation, interacting with proteins, and coding for peptides. CircRNA dysregulation has also been implicated in many cancers, such as breast cancer. Their relatively high stability and presence in bodily fluids makes cancer-associated circRNAs promising candidates as a new biomarker. In this review, we summarize the research undertaken on circRNAs associated with breast cancer, discuss circRNAs as biomarkers, and present circRNA-based therapeutic approaches.

Advances in Microfluidic Extracellular Vesicle Analysis for Cancer Diagnostics

Lab on a Chip ◽  
2021 ◽  
Author(s):  
Shibo Cheng ◽  
Yutao Li ◽  
He Yan ◽  
Yunjie Wen ◽  
Xin Zhou ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Extracellular Vesicle ◽  
Cancer Diagnostics ◽  
Bodily Fluids ◽  
Intercellular Communications

Extracellular vesicles (EVs) secreted by cells into the bloodstream and other bodily fluids, including exosomes, have been demonstrated to be a class of significant messengers that mediate intercellular communications. Tumor-derived...

scholarly journals The Emerging Role of Macrophages in Immune System Dysfunction under Real and Simulated Microgravity Conditions

2021 ◽  
Vol 22 (5) ◽  
pp. 2333
Author(s):  
Yulong Sun ◽  
Yuanyuan Kuang ◽  
Zhuo Zuo
Keyword(s):  
Immune System ◽  
Mapk Signaling ◽  
Immune Defense ◽  
Mitogen Activated Protein Kinase ◽  
Therapeutic Drugs ◽  
Physiological Processes ◽  
Immune System Dysfunction ◽  
Cell Immunity ◽  
Mitogen Activated Protein ◽  
Microgravity Conditions

In the process of exploring space, the astronaut’s body undergoes a series of physiological changes. At the level of cellular behavior, microgravity causes significant alterations, including bone loss, muscle atrophy, and cardiovascular deconditioning. At the level of gene expression, microgravity changes the expression of cytokines in many physiological processes, such as cell immunity, proliferation, and differentiation. At the level of signaling pathways, the mitogen-activated protein kinase (MAPK) signaling pathway participates in microgravity-induced immune malfunction. However, the mechanisms of these changes have not been fully elucidated. Recent studies suggest that the malfunction of macrophages is an important breakthrough for immune disorders in microgravity. As the first line of immune defense, macrophages play an essential role in maintaining homeostasis. They activate specific immune responses and participate in large numbers of physiological activities by presenting antigen and secreting cytokines. The purpose of this review is to summarize recent advances on the dysfunction of macrophages arisen from microgravity and to discuss the mechanisms of these abnormal responses. Hopefully, our work will contribute not only to the future exploration on the immune system in space, but also to the development of preventive and therapeutic drugs against the physiological consequences of spaceflight.

Liver fibrosis: extracellular vesicles mediated intercellular communication in perisinusoidal space

Hepatology ◽  
2021 ◽  
Author(s):  
Ezhilarasan Devaraj ◽  
Elumalai Perumal ◽  
Raghunandhakumar Subramaniyan ◽  
Mustapha Najimi
Keyword(s):  
Liver Fibrosis ◽  
Extracellular Vesicles ◽  
Intercellular Communication

scholarly journals Extracellular vesicles (exosomes and ectosomes) play key roles in the pathology of brain diseases

2021 ◽  
Vol 2 (1) ◽  
Author(s):  
Jacopo Meldolesi
Keyword(s):  
Multiple Sclerosis ◽  
Extracellular Vesicles ◽  
Brain Diseases ◽  
Target Cells ◽  
Surface Binding ◽  
Cells Of Origin ◽  
Relapsing Remitting ◽  
And Function ◽  
The Brain

AbstractLast century, neurons and glial cells were mostly believed to play distinct functions, relevant for the brain. Progressively, however, it became clear that neurons, astrocytes and microglia co-operate intensely with each other by release/binding of signaling factors, direct surface binding and generation/release of extracellular vesicles, the exosomes and ectosomes, called together vesicles in this abstract. The present review is focused on these vesicles, fundamental in various brain diseases. Their properties are extraordinary. The specificity of their membrane governs their fusion with distinct target cells, variable depending on the state and specificity of their cells of origin and target. Result of vesicle fusion is the discharge of their cargos into the cytoplasm of target cells. Cargos are composed of critical molecules, from proteins (various nature and function) to nucleotides (especially miRNAs), playing critical roles in immune and neurodegenerative diseases. Among immune diseases is multiple sclerosis, affected by extensive dysregulation of co-trafficking neural and glial vesicles, with distinct miRNAs inducing severe or reducing effects. The vesicle-dependent differences between progressive and relapsing-remitting forms of the disease are relevant for clinical developments. In Alzheimer’s disease the vesicles can affect the brain by changing their generation and inducing co-release of effective proteins, such Aβ and tau, from neurons and astrocytes. Specific miRNAs can delay the long-term development of the disease. Upon their traffic through the blood-brainbarrier, vesicles of various origin reach fluids where they are essential for the identification of biomarkers, important for diagnostic and therapeutic innovations, critical for the future of many brain patients.

scholarly journals Extracellular Vesicles Secreted by Mesenchymal Stromal Cells Exert Opposite Effects to Their Cells of Origin in Murine Sodium Dextran Sulfate-Induced Colitis

2021 ◽  
Vol 12 ◽  
Author(s):  
Anna Maria Tolomeo ◽  
Ignazio Castagliuolo ◽  
Martina Piccoli ◽  
Michele Grassi ◽  
Fabio Magarotto ◽  
...  
Keyword(s):  
Beneficial Effect ◽  
Extracellular Vesicles ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Dextran Sulfate ◽  
Experimental Colitis ◽  
Culture Conditions ◽  
Experimental Conditions ◽  
Intestinal Fibrosis ◽  
Cells Of Origin

Several reports have described a beneficial effect of Mesenchymal Stromal Cells (MSCs) and of their secreted extracellular vesicles (EVs) in mice with experimental colitis. However, the effects of the two treatments have not been thoroughly compared in this model. Here, we compared the effects of MSCs and of MSC-EV administration in mice with colitis induced by dextran sulfate sodium (DSS). Since cytokine conditioning was reported to enhance the immune modulatory activity of MSCs, the cells were kept either under standard culture conditions (naïve, nMSCs) or primed with a cocktail of pro-inflammatory cytokines, including IL1β, IL6 and TNFα (induced, iMSCs). In our experimental conditions, nMSCs and iMSCs administration resulted in both clinical and histological worsening and was associated with pro-inflammatory polarization of intestinal macrophages. However, mice treated with iEVs showed clinico-pathological improvement, decreased intestinal fibrosis and angiogenesis and a striking increase in intestinal expression of Mucin 5ac, suggesting improved epithelial function. Moreover, treatment with iEVs resulted in the polarization of intestinal macrophages towards and anti-inflammatory phenotype and in an increased Treg/Teff ratio at the level of the intestinal lymph node. Collectively, these data confirm that MSCs can behave either as anti- or as pro-inflammatory agents depending on the host environment. In contrast, EVs showed a beneficial effect, suggesting a more predictable behavior, a safer therapeutic profile and a higher therapeutic efficacy with respect to their cells of origin.

Zika virus hijacks extracellular vesicle tetraspanin pathways for cell-to-cell transmission

2021 ◽  
Author(s):  
Sara B. York ◽  
Li Sun ◽  
Allaura S. Cone ◽  
Leanne C. Duke ◽  
Mujeeb R. Cheerathodi ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Intercellular Communication ◽  
Zika Virus ◽  
Biological Fluids ◽  
Virus Transmission ◽  
First Trimester ◽  
Enhanced Production ◽  
Infected Cells ◽  
Encapsulated Structures

ABSTRACTExtracellular vesicles (EVs) are membrane-encapsulated structures released by cells which carry signaling factors, proteins and microRNAs that mediate intercellular communication. Accumulating evidence supports an important role of EVs in the progression of neurological conditions and both the spread and pathogenesis of infectious diseases. It has recently been demonstrated that EVs from Hepatitis C virus (HCV) infected individuals and cells contained replicative-competent viral RNA that was capable of infecting hepatocytes. Being a member of the same viral family, it is likely the Zika virus also hijacks EV pathways to package viral components and secrete vesicles that are infectious and potentially less immunogenic. As EVs have been shown to cross blood-brain and placental barriers, it is possible that Zika virus could usurp normal EV biology to gain access to the brain or developing fetus. Here, we demonstrate that Zika virus infected cells secrete distinct EV sub-populations with specific viral protein profiles and infectious genomes. Zika virus infection resulted in the enhanced production of EVs with varying sizes and density compared to those released from non-infected cells. We also show that the EV enriched tetraspanin CD63 regulates the release of EVs, and Zika viral genomes and capsids following infection. Overall, these findings provide evidence for an alternative means of Zika virus transmission and demonstrate the role of EV biogenesis and trafficking proteins in the modulation of Zika infection.ImportanceZika virus is a re-emerging infectious disease that spread rapidly across the Caribbean and South America. Infection of pregnant women during the first trimester has been linked to microcephaly, a neurological condition where babies are born with smaller heads due to abnormal brain development. Babies born with microcephaly can develop convulsions and suffer disabilities as they age. Despite the significance of Zika virus, little is known about how the virus infects the fetus or causes disease. Extracellular vesicles (EVs) are membrane-encapsulated structures released by cells that are present in all biological fluids. EVs carry signaling factors, proteins and microRNAs that mediate intercellular communication. EVs have been shown to be a means by which some viruses can alter cellular environments and cross previously unpassable cellular barriers. Thus gaining a greater understanding of how Zika affects EV cargo may aid in the development of better diagnostics, targeted therapeutics and prophylactic treatments.

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