Thomas Lener 1 , 2 , Mario Gimona 1 , 2 , Ludwig Aigner 1 , Verena Börger 3 , Edit Buzas 4 , Giovanni Camussi 5 , Nathalie Chaput 6 , 7 , Devasis Chatterjee 8 , 9 , Felipe A. Court 10 , Hernando A. del Portillo 11 , 12 , Lorraine O'Driscoll 13 , 14 , Stefano Fais 15 , Juan M. Falcon-Perez 16 , 17 , Ursula Felderhoff-Mueser 18 , Lorenzo Fraile 19 , Yong Song Gho 20 , André Görgens 3 , Ramesh C. Gupta 21 , 22 , An Hendrix 23 , Dirk M. Hermann 24 , Andrew F. Hill 25 , Fred Hochberg 26 , Peter A. Horn 3 , Dominique de Kleijn 27 , Lambros Kordelas 28 , Boris W. Kramer 29 , Eva-Maria Krämer-Albers 30 , Sandra Laner-Plamberger 1 , 2 , Saara Laitinen 31 , Tommaso Leonardi 32 , 33 , Magdalena J. Lorenowicz 34 , Sai Kiang Lim 35 , Jan Lötvall 36 , Casey A. Maguire 37 , Antonio Marcilla 38 , 39 , Irina Nazarenko 40 , Takahiro Ochiya 41 , Tushar Patel 42 , Shona Pedersen 43 , Gabriella Pocsfalvi 44 , Stefano Pluchino 32 , Peter Quesenberry 8 , 9 , Ilona G. Reischl 45 , Francisco J. Rivera 46 , Ralf Sanzenbacher 47 , Katharina Schallmoser 1 , 2 , Ineke Slaper-Cortenbach 48 , Dirk Strunk 49 , Torsten Tonn 50 , Pieter Vader 51 , 52 , Bas W. M. van Balkom 53 , Marca Wauben 54 , Samir El Andaloussi 52 , 55 , Clotilde Théry 7 , 56 , Eva Rohde 1 , 2 , * , Bernd Giebel 3 , *
31 December 2015
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.