Author
Antonio Marcilla
Other affiliations: National Institutes of Health, University of Alicante
Bio: Antonio Marcilla is an academic researcher from University of Valencia. The author has contributed to research in topics: Pyrolysis & Catalysis. The author has an hindex of 62, co-authored 372 publications receiving 19470 citations. Previous affiliations of Antonio Marcilla include National Institutes of Health & University of Alicante.
Papers published on a yearly basis
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Clotilde Théry1, Kenneth W. Witwer2, Elena Aikawa3, María José Alcaraz4 +414 more•Institutions (209)
TL;DR: The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities, and a checklist is provided with summaries of key points.
Abstract: The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.
5,988 citations
University of Helsinki1, Semmelweis University2, Hungarian Academy of Sciences3, University of Szeged4, University of Palermo5, Institute of Molecular Pathology and Immunology of the University of Porto6, University of Porto7, Autonomous University of Barcelona8, Instituto de Biologia Molecular e Celular9, Ikerbasque10, Harvard University11, University of Duisburg-Essen12, Salk Institute for Biological Studies13, Paracelsus Private Medical University of Salzburg14, University of Colorado Denver15, Bilkent University16, Middle East Technical University17, University of Southern Denmark18, Statens Serum Institut19, Ghent University Hospital20, Oslo University Hospital21, University of Belgrade22, University of Ljubljana23, University of Mainz24, Finnish Red Cross25, University of Gothenburg26, Latvian Biomedical Research and Study centre27, University of Applied Sciences and Arts Northwestern Switzerland FHNW28, University of Valencia29, Centro Nacional de Investigaciones Cardiovasculares30, University of Freiburg31, Utrecht University32, Trinity College, Dublin33, University of Barcelona34, Catalan Institution for Research and Advanced Studies35, International University Of Catalonia36, Aarhus University Hospital37
TL;DR: A comprehensive overview of the current understanding of the physiological roles of EVs is provided, drawing on the unique EV expertise of academia-based scientists, clinicians and industry based in 27 European countries, the United States and Australia.
Abstract: 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.
3,690 citations
La Trobe University1, Harvard University2, German Cancer Research Center3, Yale University4, Morehouse School of Medicine5, Autonomous University of Barcelona6, University of Massachusetts Medical School7, Semmelweis University8, Cardiff University9, Ikerbasque10, Karolinska Institutet11, Pohang University of Science and Technology12, Allahabad University13, Ghent University14, University of Melbourne15, London Metropolitan University16, Erasmus University Rotterdam17, University of Mainz18, National University of Singapore19, University of Oslo20, University of Gothenburg21, University of Valencia22, Umeå University23, University of Freiburg24, University of Amsterdam25, Utrecht University26, Johns Hopkins University27, Mayo Clinic28, Ohio State University29, University of Cambridge30, University of Zurich31, Curie Institute32, Michigan State University33, Autonomous University of Madrid34, University of Helsinki35, Aalborg University36, University of Louisville37, Carlos III Health Institute38, Centre national de la recherche scientifique39, Heidelberg University40
TL;DR: Vesiclepedia is a community-annotated compendium of molecular data on extracellular vesicles that aims to provide a single authoritative source for information on vesicle structure and function.
Abstract: Extracellular vesicles (EVs) are membraneous vesicles released by a variety of cells into their microenvironment. Recent studies have elucidated the role of EVs in intercellular communication, pathogenesis, drug, vaccine and gene-vector delivery, and as possible reservoirs of biomarkers. These findings have generated immense interest, along with an exponential increase in molecular data pertaining to EVs. Here, we describe Vesiclepedia, a manually curated compendium of molecular data (lipid, RNA, and protein) identified in different classes of EVs from more than 300 independent studies published over the past several years. Even though databases are indispensable resources for the scientific community, recent studies have shown that more than 50% of the databases are not regularly updated. In addition, more than 20% of the database links are inactive. To prevent such database and link decay, we have initiated a continuous community annotation project with the active involvement of EV researchers. The EV research community can set a gold standard in data sharing with Vesiclepedia, which could evolve as a primary resource for the field.
1,146 citations
Paracelsus Private Medical University of Salzburg1, University of Duisburg-Essen2, Semmelweis University3, University of Turin4, Institut Gustave Roussy5, Brown University6, Pontifical Catholic University of Chile7, University of Barcelona8, Trinity College, Dublin9, Istituto Superiore di Sanità10, Ikerbasque11, Pohang University of Science and Technology12, University of Louisville13, Ghent University Hospital14, La Trobe University15, Harvard University16, National University of Singapore17, Maastricht University18, University of Mainz19, University of Cambridge20, Utrecht University21, Agency for Science, Technology and Research22, University of Gothenburg23, University of Valencia24, University of Freiburg25, Aalborg University26, National Research Council27, Paul Ehrlich Institute28, German Red Cross29, University of Oxford30, Karolinska Institutet31
TL;DR: In this paper, the authors summarize recent developments and the current knowledge of extracellular vesicles (EVs) and discuss safety and regulatory requirements that must be considered for pharmaceutical manufacturing and clinical application.
Abstract: Extracellular vesicles (EVs), such as exosomes and microvesicles, are released by different cell types and participate in physiological and pathophysiological processes. EVs mediate intercellular communication as cell-derived extracellular signalling organelles that transmit specific information from their cell of origin to their target cells. As a result of these properties, EVs of defined cell types may serve as novel tools for various therapeutic approaches, including (a) anti-tumour therapy, (b) pathogen vaccination, (c) immune-modulatory and regenerative therapies and (d) drug delivery. The translation of EVs into clinical therapies requires the categorization of EV-based therapeutics in compliance with existing regulatory frameworks. As the classification defines subsequent requirements for manufacturing, quality control and clinical investigation, it is of major importance to define whether EVs are considered the active drug components or primarily serve as drug delivery vehicles. For an effective and particularly safe translation of EV-based therapies into clinical practice, a high level of cooperation between researchers, clinicians and competent authorities is essential. In this position statement, basic and clinical scientists, as members of the International Society for Extracellular Vesicles (ISEV) and of the European Cooperation in Science and Technology (COST) program of the European Union, namely European Network on Microvesicles and Exosomes in Health and Disease (ME-HaD), summarize recent developments and the current knowledge of EV-based therapies. Aspects of safety and regulatory requirements that must be considered for pharmaceutical manufacturing and clinical application are highlighted. Production and quality control processes are discussed. Strategies to promote the therapeutic application of EVs in future clinical studies are addressed.
954 citations
Istituto Superiore di Sanità1, Trinity College, Dublin2, Autonomous University of Barcelona3, Semmelweis University4, University of Turin5, University of Palermo6, University of Porto7, University of Barcelona8, University of Oxford9, Karolinska Institutet10, Ghent University11, Bilkent University12, University of Ljubljana13, University of Nantes14, University of Belgrade15, University of Ioannina16, University of Applied Sciences and Arts Northwestern Switzerland FHNW17, University of Valencia18, ORT Braude College of Engineering19, Oslo University Hospital20, University of Freiburg21, National Research Council22, University of Zurich23, Centre national de la recherche scientifique24, Innsbruck Medical University25, University of Helsinki26, Autonomous University of Madrid27, University of Duisburg-Essen28
TL;DR: The high potential of nanosized EVs for both diagnostic and therapeutic areas of nanomedicine, as demonstrated by the European Network on Microvesicles and Exosomes in Health and Disease (ME-HAD), is demonstrated.
Abstract: Recent research has demonstrated that all body fluids assessed contain substantial amounts of vesicles that range in size from 30 to 1000 nm and that are surrounded by phospholipid membranes containing different membrane microdomains such as lipid rafts and caveolae. The most prominent representatives of these so-called extracellular vesicles (EVs) are nanosized exosomes (70-150 nm), which are derivatives of the endosomal system, and microvesicles (100-1000 nm), which are produced by outward budding of the plasma membrane. Nanosized EVs are released by almost all cell types and mediate targeted intercellular communication under physiological and pathophysiological conditions. Containing cell-type-specific signatures, EVs have been proposed as biomarkers in a variety of diseases. Furthermore, according to their physical functions, EVs of selected cell types have been used as therapeutic agents in immune therapy, vaccination trials, regenerative medicine, and drug delivery. Undoubtedly, the rapidly emerging field of basic and applied EV research will significantly influence the biomedicinal landscape in the future. In this Perspective, we, a network of European scientists from clinical, academic, and industry settings collaborating through the H2020 European Cooperation in Science and Technology (COST) program European Network on Microvesicles and Exosomes in Health and Disease (ME-HAD), demonstrate the high potential of nanosized EVs for both diagnostic and therapeutic (i.e., theranostic) areas of nanomedicine.
371 citations
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TL;DR: This review focuses on the characterization of EVs and on currently proposed mechanisms for their formation, targeting, and function.
Abstract: 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.
6,141 citations
Clotilde Théry1, Kenneth W. Witwer2, Elena Aikawa3, María José Alcaraz4 +414 more•Institutions (209)
TL;DR: The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities, and a checklist is provided with summaries of key points.
Abstract: The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.
5,988 citations
TL;DR: A review of the recent developments in the wood pyrolysis and reports the characteristics of the resulting bio-oils, which are the main products of fast wood pyrotechnics, can be found in this paper.
Abstract: Fast pyrolysis utilizes biomass to produce a product that is used both as an energy source and a feedstock for chemical production. Considerable efforts have been made to convert wood biomass to liquid fuels and chemicals since the oil crisis in mid-1970s. This review focuses on the recent developments in the wood pyrolysis and reports the characteristics of the resulting bio-oils, which are the main products of fast wood pyrolysis. Virtually any form of biomass can be considered for fast pyrolysis. Most work has been performed on wood, because of its consistency and comparability between tests. However, nearly 100 types of biomass have been tested, ranging from agricultural wastes such as straw, olive pits, and nut shells to energy crops such as miscanthus and sorghum. Forestry wastes such as bark and thinnings and other solid wastes, including sewage sludge and leather wastes, have also been studied. In this review, the main (although not exclusive) emphasis has been given to wood. The literature on woo...
4,988 citations
TL;DR: Extracellular vesicles are now considered as an additional mechanism for intercellular communication, allowing cells to exchange proteins, lipids and genetic material.
Abstract: Extracellular vesicles are a heterogeneous group of cell-derived membranous structures comprising exosomes and microvesicles, which originate from the endosomal system or which are shed from the plasma membrane, respectively They are present in biological fluids and are involved in multiple physiological and pathological processes Extracellular vesicles are now considered as an additional mechanism for intercellular communication, allowing cells to exchange proteins, lipids and genetic material Knowledge of the cellular processes that govern extracellular vesicle biology is essential to shed light on the physiological and pathological functions of these vesicles as well as on clinical applications involving their use and/or analysis However, in this expanding field, much remains unknown regarding the origin, biogenesis, secretion, targeting and fate of these vesicles
4,241 citations
TL;DR: Exosomes were described as vesicles of endosomal origin secreted from reticulocytes in the 1980s as discussed by the authors, and their biogenesis, their secretion, and their subsequent fate are discussed, as their functions rely on these important processes.
Abstract: In the 1980s, exosomes were described as vesicles of endosomal origin secreted from reticulocytes. Interest increased around these extracellular vesicles, as they appeared to participate in several cellular processes. Exosomes bear proteins, lipids, and RNAs, mediating intercellular communication between different cell types in the body, and thus affecting normal and pathological conditions. Only recently, scientists acknowledged the difficulty of separating exosomes from other types of extracellular vesicles, which precludes a clear attribution of a particular function to the different types of secreted vesicles. To shed light into this complex but expanding field of science, this review focuses on the definition of exosomes and other secreted extracellular vesicles. Their biogenesis, their secretion, and their subsequent fate are discussed, as their functions rely on these important processes.
3,959 citations