Extracellular Vesicles – the next frontier in endocrinology

Endocrinology ◽  
2021 ◽  
Author(s):  
Anasuya Das Gupta ◽  
Natalia Krawczynska ◽  
Erik R Nelson
Keyword(s):  
Extracellular Vesicles ◽  
Endocrine System ◽  
Cell Types ◽  
Target Cells ◽  
Cell Physiology ◽  
Disease States ◽  
Membrane Bound ◽  
Functional Biology ◽  
Regulation Of Secretion ◽  
Different Cell Types

Abstract Extracellular vesicles (EVs) including exosomes are emerging as important carriers of signals in normal and patho- physiology. As EVs are a long-range communication or signaling modality – just like hormones are, the field of endocrinology is uniquely poised to offer insight into their functional biology and regulation. EVs are membrane bound particles secreted by many different cell types and can have local or systemic effects, being transported in body fluids. They express trans-membrane proteins, some of which are shared between EVs and some being specific to the tissue of origin, that can interact with target cells directly (much like hormones can). They also contain cargo within them that includes DNA, RNA, miRNA and various metabolites. They can fuse with target cells to empty their cargo and alter their target cell physiology in this way too. Similar to the endocrine system, the EV system is likely to be under homeostatic control, making the regulation of their biogenesis and secretion important aspects to study. In this review, we briefly highlight select examples of how EVs are implicated in normal physiology and disease states. We also discuss what is known about their biogenesis and regulation of secretion. We hope that this paper inspires the endocrinology field to use our collective expertise to explore these new multi-modal ‘hormones’.

scholarly journals Fostering “Education”: Do Extracellular Vesicles Exploit Their Own Delivery Code?

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1741
Author(s):  
Mayra Paolillo ◽  
Sergio Comincini ◽  
Sergio Schinelli
Keyword(s):  
Extracellular Vesicles ◽  
Intercellular Communication ◽  
Surface Membrane ◽  
Cell Types ◽  
Future Research ◽  
Target Cells ◽  
Bioinformatic Tools ◽  
Experimental Approaches ◽  
Different Cell Types

Extracellular vesicles (EVs), comprising large microvesicles (MVs) and exosomes (EXs), play a key role in intercellular communication, both in physiological and in a wide variety of pathological conditions. However, the education of EV target cells has so far mainly been investigated as a function of EX cargo, while few studies have focused on the characterization of EV surface membrane molecules and the mechanisms that mediate the addressability of specific EVs to different cell types and tissues. Identifying these mechanisms will help fulfill the diagnostic, prognostic, and therapeutic promises fueled by our growing knowledge of EVs. In this review, we first discuss published studies on the presumed EV “delivery code” and on the combinations of the hypothesized EV surface membrane “sender” and “recipient” molecules that may mediate EV targeting in intercellular communication. Then we briefly review the main experimental approaches and techniques, and the bioinformatic tools that can be used to identify and characterize the structure and functional role of EV surface membrane molecules. In the final part, we present innovative techniques and directions for future research that would improve and deepen our understandings of EV-cell targeting.

An Overview of the Latest Applications of Platelet-Derived Microparticles and Nanoparticles in Medical Technology 2010-2020

2021 ◽  
Vol 21 ◽  
Author(s):  
Tahereh Zadeh Mehrizi
Keyword(s):  
Drug Delivery ◽  
Cell Types ◽  
Current Status ◽  
Target Cells ◽  
Interesting Point ◽  
Large Size ◽  
Review Study ◽  
Cellular Pathways ◽  
Different Cell Types

: Today, Platelets and platelet-derived nanoparticles and microparticles have found many applications in nanomedical technology. The results of our review study show that no article has been published in this field to review the current status of applications of these platelet derivatives so far. Therefore, in present study, our goal is to compare the applications of platelet derivatives and review their latest status between 2010 and 2020 to present the latest findings to researchers. A very interesting point about the role of platelet derivatives is the presence of molecules on their surface which makes them capable of hiding from the immune system, reaching different target cells, and specifically attaching to different cell types. According to the results of this study, most of their applications include drug delivery, diagnosis of various diseases, and tissue engineering. However, their application in drug delivery is limited due to heterogeneity, large size, and the possibility of interference with cellular pathways in microparticles derived from other cells. On the other hand, platelet nanoparticles are more controllable and have been widely used for drug delivery in treatment of cancer, atherosclerosis, thrombosis, infectious diseases, repair of damaged tissue, and photothermal therapy. The results of this study show that platelet nanoparticles are more controllable than platelet microparticles and have a higher potential for use in medicine.

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 Extracellular Vesicles as Biological Shuttles for Targeted Therapies

2019 ◽  
Vol 20 (8) ◽  
pp. 1848 ◽  
Author(s):  
Stefania Raimondo ◽  
Gianluca Giavaresi ◽  
Aurelio Lorico ◽  
Riccardo Alessandro
Keyword(s):  
Extracellular Vesicles ◽  
Therapeutic Agents ◽  
Bioactive Molecules ◽  
Target Cells ◽  
Special Focus ◽  
Pathological Conditions ◽  
Critical Issues ◽  
Membrane Bound ◽  
And Function ◽  
Potential Use

The development of effective nanosystems for drug delivery represents a key challenge for the improvement of most current anticancer therapies. Recent progress in the understanding of structure and function of extracellular vesicles (EVs)—specialized membrane-bound nanocarriers for intercellular communication—suggests that they might also serve as optimal delivery systems of therapeutics. In addition to carrying proteins, lipids, DNA and different forms of RNAs, EVs can be engineered to deliver specific bioactive molecules to target cells. Exploitation of their molecular composition and physical properties, together with improvement in bio-techniques to modify their content are critical issues to target them to specific cells/tissues/organs. Here, we will discuss the current developments in the field of animal and plant-derived EVs toward their potential use for delivery of therapeutic agents in different pathological conditions, with a special focus on cancer.

scholarly journals Stem cells and extracellular vesicles: biological regulators of physiology and disease

2019 ◽  
Vol 317 (2) ◽  
pp. C155-C166 ◽  
Author(s):  
Theodor Borgovan ◽  
Lorin Crawford ◽  
Chibuikem Nwizu ◽  
Peter Quesenberry
Keyword(s):  
Stem Cells ◽  
Extracellular Vesicles ◽  
Cell Types ◽  
Target Cells ◽  
Malignant Phenotype ◽  
Marrow Mesenchymal Stem Cells ◽  
Physiological Homeostasis ◽  
Clinical Advances ◽  
Machine Learning Models

Many different subpopulations of subcellular extracellular vesicles (EVs) have been described. EVs are released from all cell types and have been shown to regulate normal physiological homeostasis, as well as pathological states by influencing cell proliferation, differentiation, organ homing, injury and recovery, as well as disease progression. In this review, we focus on the bidirectional actions of vesicles from normal and diseased cells on normal or leukemic target cells; and on the leukemic microenvironment as a whole. EVs from human bone marrow mesenchymal stem cells (MSC) can have a healing effect, reversing the malignant phenotype in prostate and colorectal cancer, as well as mitigating radiation damage to marrow. The role of EVs in leukemia and their bimodal cross talk with the encompassing microenvironment remains to be fully characterized. This may provide insight for clinical advances via the application of EVs as potential therapy and the employment of statistical and machine learning models to capture the pleiotropic effects EVs endow to a dynamic microenvironment, possibly allowing for precise therapeutic intervention.

Extracellular vesicles : novel mediators of conceptus-maternal interactions in sheep

2018 ◽  
Author(s):  
◽  
Gregory W. Burns
Keyword(s):  
Extracellular Vesicles ◽  
Pregnancy Loss ◽  
Cell Types ◽  
Target Cells ◽  
Uterine Receptivity ◽  
Mediated Communication ◽  
University Of Missouri ◽  
Dynamic Component ◽  
Uterine Endometrium ◽  
Endometrial Epithelium

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Infertility and pregnancy loss are common problems affecting reproductive efficiency, health and development in livestock. Pregnancy loss occurs most commonly during the first weeks of gestation and may arise due to asynchrony between the conceptus and uterus or endometrial dysfunction, resulting in defective conceptus elongation, implantation and/or placentation. Extracellular vesicles (EVs), a term including exosomes and microvesicles, are membrane-bound nanoparticles released from diverse cell types that deliver nucleic acids and proteins to target cells. Available studies support the central hypothesis that EVs are a component of uterine histotroph and mediate crosstalk between the developing conceptus and uterine endometrium prior to implantation. Studies were conducted here to: (1) identify and characterize EVs from uterine flush of cyclic and pregnant ewes; (2) examine potential of vesicle mediated communication during early pregnancy from endometrium and elongating conceptus derived EVs; and (3) determine progesterone regulation of EV cargo, endometrial gene expression, and total EV number in the uterine lumen of cyclic sheep. Results from these studies established that: (1) EVs are a component of the uterine histotroph in sheep with pregnancy associated differences; (2) EVs emanate from the uterine endometrium and elongating conceptus; (3) the endometrial epithelium and conceptus trophectoderm uptake labeled EVs indicating a role in intercellular communication during the establishment of pregnancy; (4) uterine EV content increases more than five-fold from day 10 to 14 of the estrous cycle; (5) the endometrial epithelia produce EVs with multivesicular endosomes, the progenitors of EVs, localized to the luminal and glandular epithelium; and (6) progesterone treatment increases the number of uterine EVs and alters their miRNA cargo. Collectively, these studies have established that EVs are a dynamic component of the uterine histotroph, produced by both the uterine epithelium and conceptus trophectoderm, with the ability to traffic between maternal and embryonic tissues and support the idea that EVs mediate communication that underpins conceptus development required for the successful establishment of pregnancy. These studies provide evidence of EVs as novel mediators of communication between the developing conceptus and endometrium. Uterine EVs may provide useful biomarkers for uterine receptivity or indicate endometrial dysfunction given their dynamic cargo and robust stability in biofluids.

scholarly journals Microbial extracellular RNAs and their roles in human diseases

2020 ◽  
Vol 245 (10) ◽  
pp. 845-850 ◽  
Author(s):  
Heon-Jin Lee
Keyword(s):  
Extracellular Vesicles ◽  
Cell Types ◽  
Human Cells ◽  
The Body ◽  
Human Diseases ◽  
Host Responses ◽  
Target Cells ◽  
Extracellular Rna ◽  
Communication Signals ◽  
Novel Therapeutic Strategies

Extracellular RNAs (exRNAs) are released by extracellular vesicles, small membranous nanoparticles secreted by all cell types. When transported into cells, exRNAs can modulate gene expression or cellular responses in the target cells since many small RNAs have regulatory functions. Indeed, it is widely acknowledged that endogenous exRNAs in the human body are related to various diseases. However, microbial exRNAs have been less studied, and their connection to host diseases has just begun to be explored. In this review, I will discuss analytical methods for exRNAs and the potential use of exRNAs as disease biomarkers. I also consider current progress in understanding the regulation of host mechanisms by microbial exRNAs as inter-kingdom communication, efforts to utilize extracellular vesicles as therapeutic vehicles loaded with engineered RNA cargos, and a putative connection between microbial exRNA-based regulation of host responses and human diseases such as Alzheimer’s. This overview aims to present novel insights into pathogenesis with regard to the function of microbial exRNAs as “disease-relevant travelers.” Impact statement The number of commensal bacteria in the body surpasses the number of actual human cells. Thus, various interactions between microbes and human cells constitute an inevitable phenomenon. Recent evidence has led to bacterial extracellular RNAs (exRNAs) being proposed as good candidates for microbe–host inter-kingdom communication tools as they can modulate the expression of host genes. However, research findings on the relevance of interactions between extracellular RNA and human diseases are still in their infancy. Nevertheless, substantial data suggest that microbial exRNAs are implicated in various human diseases both at local and distant sites. By exploring various scenarios for the involvement of microbial exRNAs in human diseases, we may better understand the role of exRNAs as “communication signals” for diseases and thereby develop novel therapeutic strategies by using them and their carrier extracellular vesicles.

Comparative studies of insulin binding to receptor from adipocytes, hepatocytes, monocytes and erythrocytes from the pig

1988 ◽  
Vol 118 (1) ◽  
pp. 59-67 ◽  
Author(s):  
Elisabeth Hjøllund ◽  
Bjørn Richelsen ◽  
Oluf Pedersen
Keyword(s):  
Steady State ◽  
Receptor Binding ◽  
Specific Binding ◽  
Insulin Binding ◽  
Cell Types ◽  
Target Cells ◽  
Suitable Model ◽  
The Individual ◽  
Different Cell Types ◽  
Specific Insulin

Abstract. We have described the receptor binding of A 14-labelled [125I]insulin to viable adipocytes, hepatocytes, monocytes and erythrocytes from the pig. For all cell types the binding was of high affinity, specific for insulin, the non-specific binding low and degradation of insulin in the medium was minimal. At 24°C, steady state insulin binding was achieved in all four cell types. At 37°C, steady state insulin binding could be measured to adipocytes and hepatocytes. Specific insulin binding levels and receptor affinity for blood and fat cells from the pig are comparable to that in human cells, whereas differences, especially according to affinity, exist between pig and rat cell insulin receptor binding. It is therefore concluded that the pig is a more suitable model for studies of insulin binding in man than rodents. Finally, no correlations between the individual binding levels to the different cell types were observed. Hence, measurement of insulin binding to the easier available blood cells cannot replace studies of insulin binding to target cells of insulin.

Extracellular vesicles in the circulation: are erythrocyte microvesicles a confounder in the plasma haemoglobin assay?

2013 ◽  
Vol 41 (1) ◽  
pp. 288-292 ◽  
Author(s):  
Karen M.K. de Vooght ◽  
Cedric Lau ◽  
Pim P.M. de Laat ◽  
Richard van Wijk ◽  
Wouter W. van Solinge ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Formation Rate ◽  
Haemoglobin Concentration ◽  
Cell Types ◽  
Total Cell ◽  
Plasma Haemoglobin ◽  
Free Plasma Haemoglobin ◽  
Free Haemoglobin ◽  
Different Cell Types ◽  
Free Plasma

Blood contains a mixture of extracellular vesicles from different cell types, primarily platelets, endothelial cells, leucocytes and erythrocytes. Erythrocytes are the most abundant cell type in blood and could, especially in certain pathologies, represent an important source of vesicles. Since erythrocytes contain the haemoglobin components iron and haem, which are potentially toxic, it is important to investigate the contribution of vesicle-associated haemoglobin to total cell-free haemoglobin levels. To our knowledge, this is the first time that cell-free plasma haemoglobin has been differentiated into vesicle-associated and molecular species. We investigated the contribution of vesicle-associated haemoglobin in residual patient material that was routinely analysed for total cell-free plasma haemoglobin. All patient samples included in the study were haemolytic with total cell-free haemoglobin concentration ranging from 80 to 2500 mg/l. In the majority of the samples, total cell-free haemoglobin concentration was between 100 and 200 mg/l. No haemoglobin could be detected in the vesicle fraction, indicating that the contribution of vesicle-associated haemoglobin to total cell free-haemoglobin levels in plasma is negligible. It is important to investigate whether erythrocyte vesicles are not formed in blood or that their production is not increased during pathologies associated with haemolysis or that the clearance rate of the vesicles surpasses the formation rate.

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