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      Experimental limitations of extracellular vesicle-based therapies for the treatment of myocardial infarction

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          Abstract

          Extracellular vesicles (EVs) are particles secreted by a vast variety of cells and are often recognised to mimic the properties of their parent cell, as such those derived from developmental sources hold promise for the treatment of various diseases including myocardial infarction (MI). Here we review the experimental approaches taken for assessing the therapeutic efficacy of EVs for MI and find overt shortcomings regarding purity of isolated EVs, quantitation, dosing, EV labelling/uptake, route of administration and use of appropriate controls that renders much of the data uninterpretable. Overall, the EV/MI field has suffered from experimental approaches that are not fully standardised or validated. Fundamental improvements in EV study design are required to improve interpretation of efficacy and to ensure reproducibility and comparability across preclinical MI studies.

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          Most cited references65

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          Extracellular vesicles: Exosomes, microvesicles, and friends

          Cells release into the extracellular environment diverse types of membrane vesicles of endosomal and plasma membrane origin called exosomes and microvesicles, respectively. These extracellular vesicles (EVs) represent an important mode of intercellular communication by serving as vehicles for transfer between cells of membrane and cytosolic proteins, lipids, and RNA. Deficiencies in our knowledge of the molecular mechanisms for EV formation and lack of methods to interfere with the packaging of cargo or with vesicle release, however, still hamper identification of their physiological relevance in vivo. In this review, we focus on the characterization of EVs and on currently proposed mechanisms for their formation, targeting, and function.
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            Biological properties of extracellular vesicles and their physiological functions

            In the past decade, extracellular vesicles (EVs) have been recognized as potent vehicles of intercellular communication, both in prokaryotes and eukaryotes. This is due to their capacity to transfer proteins, lipids and nucleic acids, thereby influencing various physiological and pathological functions of both recipient and parent cells. While intensive investigation has targeted the role of EVs in different pathological processes, for example, in cancer and autoimmune diseases, the EV-mediated maintenance of homeostasis and the regulation of physiological functions have remained less explored. Here, we provide a comprehensive overview of the current understanding of the physiological roles of EVs, which has been written by crowd-sourcing, drawing on the unique EV expertise of academia-based scientists, clinicians and industry based in 27 European countries, the United States and Australia. This review is intended to be of relevance to both researchers already working on EV biology and to newcomers who will encounter this universal cell biological system. Therefore, here we address the molecular contents and functions of EVs in various tissues and body fluids from cell systems to organs. We also review the physiological mechanisms of EVs in bacteria, lower eukaryotes and plants to highlight the functional uniformity of this emerging communication system.
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              Membrane vesicles as conveyors of immune responses.

              In multicellular organisms, communication between cells mainly involves the secretion of proteins that then bind to receptors on neighbouring cells. But another mode of intercellular communication - the release of membrane vesicles - has recently become the subject of increasing interest. Membrane vesicles are complex structures composed of a lipid bilayer that contains transmembrane proteins and encloses soluble hydrophilic components derived from the cytosol of the donor cell. These vesicles have been shown to affect the physiology of neighbouring recipient cells in various ways, from inducing intracellular signalling following binding to receptors to conferring new properties after the acquisition of new receptors, enzymes or even genetic material from the vesicles. This Review focuses on the role of membrane vesicles, in particular exosomes, in the communication between immune cells, and between tumour and immune cells.
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                Author and article information

                Contributors
                Journal
                Trends Cardiovasc Med
                Trends Cardiovasc Med
                Trends in Cardiovascular Medicine
                Elsevier Science Publishing
                1050-1738
                1873-2615
                1 October 2021
                October 2021
                : 31
                : 7
                : 405-415
                Affiliations
                [a ]Department of Physiology, Anatomy & Genetics, University of Oxford. Sherrington Building, South Parks Road, Oxford OX1 3PT, United Kingdom
                [b ]Department of Chemistry, University of Oxford. Chemistry Research Laboratory, Mansfield Road, Oxford OX1 3TA, United Kingdom
                [c ]Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, United Kingdom
                Author notes
                [* ]Corresponding author. paul.riley@ 123456dpag.ox.ac.uk
                Article
                S1050-1738(20)30108-0
                10.1016/j.tcm.2020.08.003
                8501308
                32822840
                f8e9ad43-98f6-465d-8dbb-02928d9c1a07
                © 2020 The Author(s). Published by Elsevier Inc.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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                Categories
                Article

                Cardiovascular Medicine
                extracellular vesicles,myocardial infarction,isolation,characterisation,dosing and uptake,mode-of-action,preclinical studies

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