Extracellular Vesicles in Feto–Maternal Crosstalk and Pregnancy Disorders

Extracellular vesicles (EVs) actively participate in inter-cellular crosstalk and have progressively emerged as key players of organized communities of cells within multicellular organisms in health and disease. For these reasons, EVs are attracting the attention of many investigators across different biomedical fields. In this scenario, the possibility to study specific placental-derived EVs in the maternal peripheral blood may open novel perspectives in the development of new early biomarkers for major obstetric pathological conditions. Here we reviewed the involvement of EVs in feto–maternal crosstalk mechanisms, both in physiological and pathological conditions (preeclampsia, fetal growth restriction, preterm labor, gestational diabetes mellitus), also underlining the usefulness of EV characterization in maternal–fetal medicine.

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A System of Cytokines Encapsulated in ExtraCellular Vesicles

Scientific Reports ◽

10.1038/s41598-018-27190-x ◽

2018 ◽

Vol 8 (1) ◽

Cited By ~ 77

Author(s):

Wendy Fitzgerald ◽

Michael L. Freeman ◽

Michael M. Lederman ◽

Elena Vasilieva ◽

Roberto Romero ◽

...

Keyword(s):

Extracellular Vesicles ◽

Ex Vivo ◽

Biological Effects ◽

Cell Communication ◽

Health And Disease ◽

Mediate Cell ◽

Multicellular Organisms ◽

Cell Cell

Abstract Cytokines are soluble factors that mediate cell–cell communications in multicellular organisms. Recently, another system of cell–cell communication was discovered, which is mediated by extracellular vesicles (EVs). Here, we demonstrate that these two systems are not strictly separated, as many cytokines in vitro, ex vivo, and in vivo are released in EV-encapsulated forms and are capable of eliciting biological effects upon contact with sensitive cells. Association with EVs is not necessarily a property of a particular cytokine but rather of a biological system and can be changed upon system activation. EV-encapsulated cytokines were not detected by standard cytokine assays. Deciphering the regulatory mechanisms of EV-encapsulation will lead to a better understanding of cell–cell communications in health and disease.

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Extracellular Vesicles as Signaling Mediators and Disease Biomarkers across Biological Barriers

International Journal of Molecular Sciences ◽

10.3390/ijms21072514 ◽

2020 ◽

Vol 21 (7) ◽

pp. 2514 ◽

Cited By ~ 9

Author(s):

Pasquale Simeone ◽

Giuseppina Bologna ◽

Paola Lanuti ◽

Laura Pierdomenico ◽

Maria Teresa Guagnano ◽

...

Keyword(s):

Extracellular Vesicles ◽

Biological Significance ◽

Biological Information ◽

Intercellular Signaling ◽

Signal Transducers ◽

Shuttle Vectors ◽

Disease Biomarkers ◽

Neural Communication ◽

Health And Disease ◽

Multicellular Organisms

Extracellular vesicles act as shuttle vectors or signal transducers that can deliver specific biological information and have progressively emerged as key regulators of organized communities of cells within multicellular organisms in health and disease. Here, we survey the evolutionary origin, general characteristics, and biological significance of extracellular vesicles as mediators of intercellular signaling, discuss the various subtypes of extracellular vesicles thus far described and the principal methodological approaches to their study, and review the role of extracellular vesicles in tumorigenesis, immunity, non-synaptic neural communication, vascular-neural communication through the blood-brain barrier, renal pathophysiology, and embryo-fetal/maternal communication through the placenta.

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Glia-Derived Extracellular Vesicles: Role in Central Nervous System Communication in Health and Disease

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2020.623771 ◽

2021 ◽

Vol 8 ◽

Author(s):

Cristiana Pistono ◽

Nea Bister ◽

Iveta Stanová ◽

Tarja Malm

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Extracellular Vesicles ◽

Glial Cells ◽

Current Knowledge ◽

Physiological State ◽

General Term ◽

Pathological Conditions ◽

The Central Nervous System ◽

Health And Disease

Glial cells are crucial for the maintenance of correct neuronal functionality in a physiological state and intervene to restore the equilibrium when environmental or pathological conditions challenge central nervous system homeostasis. The communication between glial cells and neurons is essential and extracellular vesicles (EVs) take part in this function by transporting a plethora of molecules with the capacity to influence the function of the recipient cells. EVs, including exosomes and microvesicles, are a heterogeneous group of biogenetically distinct double membrane-enclosed vesicles. Once released from the cell, these two types of vesicles are difficult to discern, thus we will call them with the general term of EVs. This review is focused on the EVs secreted by astrocytes, oligodendrocytes and microglia, aiming to shed light on their influence on neurons and on the overall homeostasis of the central nervous system functions. We collect evidence on neuroprotective and homeostatic effects of glial EVs, including neuronal plasticity. On the other hand, current knowledge of the detrimental effects of the EVs in pathological conditions is addressed. Finally, we propose directions for future studies and we evaluate the potential of EVs as a therapeutic treatment for neurological disorders.

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Plant-Derived Extracellular Vesicles: Current Findings,Challenges, and Future Applications

Membranes ◽

10.3390/membranes11060411 ◽

2021 ◽

Vol 11 (6) ◽

pp. 411

Author(s):

Nader Kameli ◽

Anya Dragojlovic-Kerkache ◽

Paul Savelkoul ◽

Frank R. Stassen

Keyword(s):

Human Health ◽

Extracellular Vesicles ◽

Preliminary Results ◽

In Vivo Experiments ◽

Health And Disease ◽

Conducting Research ◽

Protocol Standardization ◽

Insight Into

In recent years, plant-derived extracellular vesicles (PDEVs) have gained the interest of many experts in fields such as microbiology and immunology, and research in this field has exponentially increased. These nano-sized particles have provided researchers with a number of interesting findings, making their application in human health and disease very promising. Both in vitro and in vivo experiments have shown that PDEVs can exhibit a multitude of effects, suggesting that these vesicles may have many potential future applications, including therapeutics and nano-delivery of compounds. While the preliminary results are promising, there are still some challenges to face, such as a lack of protocol standardization, as well as knowledge gaps that need to be filled. This review aims to discuss various aspects of PDEV knowledge, including their preliminary findings, challenges, and future uses, giving insight into the complexity of conducting research in this field.

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Cell-to-Cell Communication by Host-Released Extracellular Vesicles in the Gut: Implications in Health and Disease

International Journal of Molecular Sciences ◽

10.3390/ijms22042213 ◽

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.

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Exosomal Cargo May Hold the Key to Improving Reproductive Outcomes in Dairy Cows

International Journal of Molecular Sciences ◽

10.3390/ijms22042024 ◽

2021 ◽

Vol 22 (4) ◽

pp. 2024

Author(s):

Natalie Turner ◽

Pevindu Abeysinghe ◽

Pawel Sadowski ◽

Murray D. Mitchell

Keyword(s):

Mass Spectrometry ◽

Dairy Cows ◽

Bioactive Peptides ◽

Cell Types ◽

Dairy Herds ◽

Dairy Farmers ◽

Early Biomarkers ◽

Health And Disease ◽

Place Of Origin ◽

Quantitative Profiling

The reproductive status of dairy cows remains a challenge for dairy farmers worldwide, with impaired fertility linked to a significant reduction in herd profitability, due in part to impaired immunity, increased metabolic pressure, and longer postpartum anestrous interval (PPAI). Exosomes are nanovesicles released from a variety of cell types and end up in circulation, and carry proteins, bioactive peptides, lipids, and nucleic acids specific to the place of origin. As such, their role in health and disease has been investigated in humans and animals. This review discusses research into exosomes in the context of reproduction in dairy herds and introduces recent advances in mass-spectrometry (MS) based proteomics that have a potential to advance quantitative profiling of exosomal protein cargo in a search for early biomarkers of cattle fertility.

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The Role of 5-Lipoxygenase and Leukotrienes in Shock and Ischemia-Reperfusion Injury

The Scientific World JOURNAL ◽

10.1100/tsw.2007.34 ◽

2007 ◽

Vol 7 ◽

pp. 56-74 ◽

Cited By ~ 5

Author(s):

Antonietta Rossi ◽

Carlo Pergola ◽

Salvatore Cuzzocrea ◽

Lidia Sautebin

Keyword(s):

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Biological Activities ◽

Ischemia Reperfusion ◽

Targeted Disruption ◽

Pathological Conditions ◽

Metabolic Products ◽

Important Regulator ◽

Multicellular Organisms

The leukotrienes (LTs) are metabolic products of arachidonic acid via the 5-lipoxygenase (5-LO) pathway. The biological activities of LTs suggest that they are mediators of acute inflammatory and immediate hypersensitivity responses. In particular, the 5-LO activation has been proposed to be an important regulator for pathogenesis in multicellular organisms. The role of LTs in tissue damage, associated with septic and nonseptic shock and ischemia-reperfusion, has been extensively studied by the use of 5-LO inhibitors, receptor antagonists, and mice with a targeted disruption of the 5-LO gene (5-LOKO). In particular, several data indicate that LTs regulate neutrophil trafficking in damaged tissue in shock and ischemia-reperfusion, mainly through the modulation of adhesion molecule expression. This concept may provide new insights into the interpretation of the protective effect of 5-LO inhibition, which may be useful in the therapy of pathological conditions associated with septic and nonseptic shock and ischemia-reperfusion injury.

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Extracellular Vesicles and Matrix Remodeling Enzymes: The Emerging Roles in Extracellular Matrix Remodeling, Progression of Diseases and Tissue Repair

Cells ◽

10.3390/cells7100167 ◽

2018 ◽

Vol 7 (10) ◽

pp. 167 ◽

Cited By ~ 52

Author(s):

Muhammad Nawaz ◽

Neelam Shah ◽

Bruna Zanetti ◽

Marco Maugeri ◽

Renata Silvestre ◽

...

Keyword(s):

Extracellular Matrix ◽

Extracellular Vesicles ◽

Tissue Repair ◽

Metabolic Diseases ◽

Bioactive Molecules ◽

Tissue Inhibitors Of Metalloproteinases ◽

Matrix Remodeling ◽

Pathological Conditions ◽

Potential Applications ◽

Non Coding Rnas

Extracellular vesicles (EVs) are membrane enclosed micro- and nano-sized vesicles that are secreted from almost every species, ranging from prokaryotes to eukaryotes, and from almost every cell type studied so far. EVs contain repertoire of bioactive molecules such as proteins (including enzymes and transcriptional factors), lipids, carbohydrates and nucleic acids including DNA, coding and non-coding RNAs. The secreted EVs are taken up by neighboring cells where they release their content in recipient cells, or can sail through body fluids to reach distant organs. Since EVs transport bioactive cargo between cells, they have emerged as novel mediators of extra- and intercellular activities in local microenvironment and inter-organ communications distantly. Herein, we review the activities of EV-associated matrix-remodeling enzymes such as matrix metalloproteinases, heparanases, hyaluronidases, aggrecanases, and their regulators such as extracellular matrix metalloproteinase inducers and tissue inhibitors of metalloproteinases as novel means of matrix remodeling in physiological and pathological conditions. We discuss how such EVs act as novel mediators of extracellular matrix degradation to prepare a permissive environment for various pathological conditions such as cancer, cardiovascular diseases, arthritis and metabolic diseases. Additionally, the roles of EV-mediated matrix remodeling in tissue repair and their potential applications as organ therapies have been reviewed. Collectively, this knowledge could benefit the development of new approaches for tissue engineering.

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