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193 results on '"El Andaloussi, S."'

1. Mesenchymal stem cell-based therapy for ischemic stroke

Author

Anderson, JD, Pham, MT, Contreras, Z, Hoon, M, Fink, KD, Johansson, HJ, Rossignol, J, Dunbar, GL, Showalter, M, Fiehn, O, Bramlett, CS, Bardini, RL, Bauer, G, Fury, B, Hendrix, KJ, Chedin, F, El-Andaloussi, S, Hwang, B, Mulligan, MS, Lehtiö, J, and Nolta, JA

Subjects
Brain Disorders, Stem Cell Research - Nonembryonic - Non-Human, Stem Cell Research - Nonembryonic - Human, Neurosciences, Transplantation, Regenerative Medicine, Aging, Stroke, Stem Cell Research, 5.2 Cellular and gene therapies, 5.1 Pharmaceuticals
Abstract

Ischemic stroke represents a major, worldwide health burden with increasing incidence. Patients affected by ischemic strokes currently have few clinically approved treatment options available. Most currently approved treatments for ischemic stroke have narrow therapeutic windows, severely limiting the number of patients able to be treated. Mesenchymal stem cells represent a promising novel treatment for ischemic stroke. Numerous studies have demonstrated that mesenchymal stem cells functionally improve outcomes in rodent models of ischemic stroke. Recent studies have also shown that exosomes secreted by mesenchymal stem cells mediate much of this effect. In the present review, we summarize the current literature on the use of mesenchymal stem cells to treat ischemic stroke. Further studies investigating the mechanisms underlying mesenchymal stem cells tissue healing effects are warranted and would be of benefit to the field.

Published
2016

3. Identification of storage conditions stabilizing extracellular vesicles pre

Author

Görgens, A, Corso, G, Hagey, DW, Jawad Wiklander, R, Gustafsson, MO, Felldin, U, Lee, Y, Bostancioglu, RB, Sork, H, Liang, X, Zheng, W, Mohammad, DK, Van de Wakker, SI, Vader, P, Zickler, AM, Mamand, DR, Ma, L, Holme, MN, Stevens, MM, Wiklander, OPB, and El Andaloussi, S

Subjects
liposomes, vesicles, diluent, preservation, Trehalose, storage buffer, exosomes, stability, 0601 Biochemistry and Cell Biology, storage, Extracellular Vesicles, Nucleic Acids, Freezing, Humans
Abstract

Extracellular vesicles (EVs) play a key role in many physiological and pathophysiological processes and hold great potential for therapeutic and diagnostic use. Despite significant advances within the last decade, the key issue of EV storage stability remains unresolved and under investigated. Here, we aimed to identify storage conditions stabilizing EVs and comprehensively compared the impact of various storage buffer formulations at different temperatures on EVs derived from different cellular sources for up to 2 years. EV features including concentration, diameter, surface protein profile and nucleic acid contents were assessed by complementary methods, and engineered EVs containing fluorophores or functionalized surface proteins were utilized to compare cellular uptake and ligand binding. We show that storing EVs in PBS over time leads to drastically reduced recovery particularly for pure EV samples at all temperatures tested, starting already within days. We further report that using PBS as diluent was found to result in severely reduced EV recovery rates already within minutes. Several of the tested new buffer conditions largely prevented the observed effects, the lead candidate being PBS supplemented with human albumin and trehalose (PBS-HAT). We report that PBS-HAT buffer facilitates clearly improved short-term and long-term EV preservation for samples stored at -80°C, stability throughout several freeze-thaw cycles, and drastically improved EV recovery when using a diluent for EV samples for downstream applications.

Published
2022

5. Influence of short term storage conditions, concentration methods and excipients on extracellular vesicle recovery and function

Author

Experimentele Afd. Cardiologie 2, Onderzoek Cardiovasculair Reg. Med., Regenerative Medicine and Stem Cells, Circulatory Health, CDL Staf Research, van de Wakker, S. I., van Oudheusden, J., Mol, E. A., Roefs, M. T., Zheng, W., Görgens, A., El Andaloussi, S., Sluijter, J. P.G., Vader, P., Experimentele Afd. Cardiologie 2, Onderzoek Cardiovasculair Reg. Med., Regenerative Medicine and Stem Cells, Circulatory Health, CDL Staf Research, van de Wakker, S. I., van Oudheusden, J., Mol, E. A., Roefs, M. T., Zheng, W., Görgens, A., El Andaloussi, S., Sluijter, J. P.G., and Vader, P.

Published
2022

7. Influence of short term storage conditions, concentration methodsand excipients on extracellular vesicle recovery and function

Author

van de Wakker, S.I., van Oudheusden, J., Mol, E.A., Roefs, M.T., Zheng, W., Görgens, A., El Andaloussi, S., Sluijter, J.P.G., and Vader, P.

Subjects
Excipients, Extracellular Vesicles, Cell Tracking, Organ Preservation Solutions, Temperature, Pharmaceutical Science, Nanoparticles, General Medicine, Organ Preservation, Cells, Cultured, Biotechnology
Abstract

Extracellular vesicles (EVs) are phospholipid bilayer enclosed vesicles which play an important role in intercellular communication. To date, many studies have focused on therapeutic application of EVs. However, to progress EV applications faster towards the clinic, more information about the physical stability and scalable production of EVs is needed. The goal of this study was to evaluate EV recovery and function after varying several conditions in the isolation process or during storage. Physical stability and recovery rates of EVs were evaluated by measuring EV size, particle and protein yields using nanoparticle tracking analysis, microBCA protein quantification assay and transmission electron microscopy. Western blot analyses of specific EV markers were performed to determine EV yields and purity. EV functionality was tested in an endothelial cell wound healing assay. Higher EV recovery rates were found when using HEPES buffered saline (HBS) as buffer compared to phosphate buffered saline (PBS) during EV isolation. When concentrating EVs, 15 ml spinfilters with a 10 kDa membrane cutoff gave the highest EV recovery. Next, EV storage in polypropylene tubes was shown to be superior compared to glass tubes. The use of protective excipients during EV storage, i.e. bovine serum albumin (BSA) and Tween 20, improved EV preservation without influencing their functionality. Finally, it was shown that both 4 °C and -80 °C are suitable for short term storage of EVs. Together, our results indicate that optimizing buffer compositions, concentrating steps, protective excipients and storage properties may collectively increase EV recovery rates significantly while preserving their functional properties, which accelerates translation of EV-based therapeutics towards clinical application.

Published
2021

8. Targeting OGG1 arrests cancer cell proliferation by inducing replication stress

Author

Visnes, T., Benítez-Buelga, C., Cázares-Körner, A., Sanjiv, K., Hanna, B. M. F., Mortusewicz, O., Rajagopal, V., Albers, J. J., Hagey, D. W., Bekkhus, T., Eshtad, S., Baquero, J. M., Masuyer, G., Wallner, O., Müller, S., Pham, T., Göktürk, C., Rasti, A., Suman, S., Torres, Raul, Sarno, A., Wiita, E., Homan, E. J., Karsten, S., Marimuthu, K., Michel, M., Koolmeister, T., Scobie, M., Loseva, O., Almlöf, I., Unterlass, J. E., Pettke, A., Boström, J., Pandey, M., Gad, H., Herr, P., Jemth, A. S., El Andaloussi, S., Kalderén, C., Rodriguez-Perales, S., Benítez, J., Krokan, H. E., Altun, M., Stenmark, P., Berglund, U. W., Helleday, T., and Universitat Autònoma de Barcelona

Subjects
DNA Replication, Guanine, DNA Repair, Poly (ADP-Ribose) Polymerase-1, Mice, Nude, Antineoplastic Agents, DNA Glycosylases, Mice, Cell Line, Tumor, Animals, Humans, Molecular Targeted Therapy, Enzyme Inhibitors, RNA, Small Interfering, Cell Proliferation, DNA, Neoplasm, HCT116 Cells, Survival Analysis, Xenograft Model Antitumor Assays, Tumor Burden, Gene Expression Regulation, Neoplastic, Oxidative Stress, Colonic Neoplasms, Reactive Oxygen Species, DNA Damage, Signal Transduction
Abstract

Altered oncogene expression in cancer cells causes loss of redox homeostasis resulting in oxidative DNA damage, e.g. 8-oxoguanine (8-oxoG), repaired by base excision repair (BER). PARP1 coordinates BER and relies on the upstream 8-oxoguanine-DNA glycosylase (OGG1) to recognise and excise 8-oxoG. Here we hypothesize that OGG1 may represent an attractive target to exploit reactive oxygen species (ROS) elevation in cancer. Although OGG1 depletion is well tolerated in non-transformed cells, we report here that OGG1 depletion obstructs A3 T-cell lymphoblastic acute leukemia growth in vitro and in vivo, validating OGG1 as a potential anti-cancer target. In line with this hypothesis, we show that OGG1 inhibitors (OGG1i) target a wide range of cancer cells, with a favourable therapeutic index compared to non-transformed cells. Mechanistically, OGG1i and shRNA depletion cause S-phase DNA damage, replication stress and proliferation arrest or cell death, representing a novel mechanistic approach to target cancer. This study adds OGG1 to the list of BER factors, e.g. PARP1, as potential targets for cancer treatment.

Published
2021

9. Targeting OGG1 arrests cancer cell proliferation by inducing replication stress

Author

Visnes, T., Benítez-Buelga, C., Cázares-Körner, A., Sanjiv, K., Hanna, B.M.F., Mortusewicz, O., Rajagopal, V., Albers, J.J., Hagey, D.W., Bekkhus, T., Eshtad, S., Baquero, J.M., Masuyer, G., Wallner, O., Müller, S., Pham, T., Göktürk, C., Rasti, A., Suman, S., Torres-Ruiz, R., Sarno, A., Wiita, E., Homan, E.J., Karsten, S., Marimuthu, K., Michel, M., Koolmeister, T., Scobie, M., Loseva, O., Almlöf, I., Unterlass, J.E., Pettke, A., Boström, J., Pandey, M., Gad, H., Herr, P., Jemth, A.-S., El Andaloussi, S., Kalderén, C., Rodriguez-Perales, S., Benítez, J., Krokan, H.E., Altun, M., Stenmark, P., Berglund, U.W., and Helleday, T.

Subjects
DNA Replication, Guanine, DNA Repair, AcademicSubjects/SCI00010, Poly (ADP-Ribose) Polymerase-1, Mice, Nude, Antineoplastic Agents, Genome Integrity, Repair and Replication, DNA Glycosylases, Mice, Cell Line, Tumor, repair and replication, Animals, Humans, Molecular Targeted Therapy, Enzyme Inhibitors, RNA, Small Interfering, Cell Proliferation, DNA, Neoplasm, HCT116 Cells, Survival Analysis, Xenograft Model Antitumor Assays, Genome integrity, Tumor Burden, Gene Expression Regulation, Neoplastic, Oxidative Stress, Colonic Neoplasms, Reactive Oxygen Species, DNA Damage, Signal Transduction
Abstract

Altered oncogene expression in cancer cells causes loss of redox homeostasis resulting in oxidative DNA damage, e.g. 8-oxoguanine (8-oxoG), repaired by base excision repair (BER). PARP1 coordinates BER and relies on the upstream 8-oxoguanine-DNA glycosylase (OGG1) to recognise and excise 8-oxoG. Here we hypothesize that OGG1 may represent an attractive target to exploit reactive oxygen species (ROS) elevation in cancer. Although OGG1 depletion is well tolerated in non-transformed cells, we report here that OGG1 depletion obstructs A3 T-cell lymphoblastic acute leukemia growth in vitro and in vivo, validating OGG1 as a potential anti-cancer target. In line with this hypothesis, we show that OGG1 inhibitors (OGG1i) target a wide range of cancer cells, with a favourable therapeutic index compared to non-transformed cells. Mechanistically, OGG1i and shRNA depletion cause S-phase DNA damage, replication stress and proliferation arrest or cell death, representing a novel mechanistic approach to target cancer. This study adds OGG1 to the list of BER factors, e.g. PARP1, as potential targets for cancer treatment. C The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

Published
2020

10. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

Author

Théry, C, Witwer, KW, Aikawa, E, Alcaraz, MJ, Anderson, JD, Andriantsitohaina, R, Antoniou, A, Arab, T, Archer, F, Atkin-Smith, GK, Ayre, DC, Bach, JM, Bachurski, D, Baharvand, H, Balaj, L, Baldacchino, S, Bauer, NN, Baxter, AA, Bebawy, M, Beckham, C, Bedina Zavec, A, Benmoussa, A, Berardi, AC, Bergese, P, Bielska, E, Blenkiron, C, Bobis-Wozowicz, S, Boilard, E, Boireau, W, Bongiovanni, A, Borràs, FE, Bosch, S, Boulanger, CM, Breakefield, X, Breglio, AM, Brennan, M, Brigstock, DR, Brisson, A, Broekman, MLD, Bromberg, JF, Bryl-Górecka, P, Buch, S, Buck, AH, Burger, D, Busatto, S, Buschmann, D, Bussolati, B, Buzás, EI, Byrd, JB, Camussi, G, Carter, DRF, Caruso, S, Chamley, LW, Chang, YT, Chaudhuri, AD, Chen, C, Chen, S, Cheng, L, Chin, AR, Clayton, A, Clerici, SP, Cocks, A, Cocucci, E, Coffey, RJ, Cordeiro-da-Silva, A, Couch, Y, Coumans, FAW, Coyle, B, Crescitelli, R, Criado, MF, D’Souza-Schorey, C, Das, S, de Candia, P, De Santana, EF, De Wever, O, del Portillo, HA, Demaret, T, Deville, S, Devitt, A, Dhondt, B, Di Vizio, D, Dieterich, LC, Dolo, V, Dominguez Rubio, AP, Dominici, M, Dourado, MR, Driedonks, TAP, Duarte, FV, Duncan, HM, Eichenberger, RM, Ekström, K, EL Andaloussi, S, Elie-Caille, C, Erdbrügger, U, Falcón-Pérez, JM, Fatima, F, Fish, JE, Flores-Bellver, M, Försönits, A, Frelet-Barrand, A, and HIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.

Subjects
ectosomes, microparticles, standardization, minimal information requirements, exosomes, guidelines, Biochemistry and Cell Biology, extracellular vesicles, microvesicles, reproducibility, rigor
Abstract

© 2018, © 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group on behalf of The International Society for Extracellular Vesicles. 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.

Published
2019

12. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

Author

Thery, C., Witwer, K. (Kenneth), Aikawa, E. (Elena), Alcaraz, M.J. (Maria Jose), Anderson, J.D. (Johnathon D), Andriantsitohaina, R. (Ramaroson), Antoniou, A. (Anna), Arab, T. (Tanina), Archer, F. (Fabienne), Atkin-Smith, G.K. (Georgia K), Ayre, D.C. (D Craig), Bach, J.-M. (Jean-Marie), Bachurski, D. (Daniel), Baharvand, H. (Hossein), Balaj, L. (Leonora), Baldacchino, S. (Shawn), Bauer, N.N. (Natalie N), Baxter, A.A. (Amy A), Bebawy, M. (Mary), Beckham, C. (Carla), Bedina Zavec, A. (Apolonija), Benmoussa, A. (Abderrahim), Berardi, A.C. (Anna C), Bergese, P. (Paolo), Bielska, E. (Ewa), Blenkiron, C. (Cherie), Bobis-Wozowicz, S. (Sylwia), Boilard, E. (Eric), Boireau, W. (Wilfrid), Bongiovanni, A. (Antonella), Borràs, F.E. (Francesc), Bosch, S. (Steffi), Boulanger, C.M. (Chantal), Breakefield, X. (Xandra), Breglio, A.M. (Andrew M), Brennan, M.Á. (Meadhbh Á), Brigstock, D.R. (David R), Brisson, A. (Alain), Broekman, M.L.D. (Marike), Bromberg, J.F. (Jacqueline F), Bryl-Górecka, P. (Paulina), Buch, S. (Shilpa), Buck, A.H. (Amy H), Burger, D. (Dylan), Busatto, S. (Sara), Buschmann, D. (Dominik), Bussolati, B. (Benedetta), Buzas, E. (Edit), Byrd, J.B. (James Bryan), Camussi, G. (Giovanni), Carter, D.R.F. (David RF), Caruso, S. (Sarah), Chamley, L.W. (Lawrence W), Chang, Y.-T. (Yu-Ting), Chaudhuri, A.D. (Amrita Datta), Chen, C. (Chihchen), Chen, S. (Shuai), Cheng, L. (Lesley), Chin, A.R. (Andrew R), Clayton, A. (Aled), Clerici, S.P. (Stefano P), Cocks, A. (Alex), Cocucci, E. (Emanuele), Coffey, R.J. (Robert J), Cordeiro-da-Silva, A. (Anabela), Couch, Y. (Yvonne), Coumans, F.A.W. (Frank AW), Coyle, B. (Beth), Crescitelli, R. (Rossella), Criado, M.F. (Miria Ferreira), D’Souza-Schorey, C. (Crislyn), Das, S. (Saumya), de Candia, P. (Paola), De Santana, E.F. (Eliezer F), De Wever, O. (Olivier), Del Portillo, H. (Hernando), Demaret, T. (Tanguy), Deville, S. (Sarah), Devitt, A. (Andrew), Dhondt, B. (Bert), Di Vizio, D. (Dolores), Dieterich, L.C. (Lothar C), Dolo, V. (Vincenza), Dominguez Rubio, A.P. (Ana Paula), Dominici, M. (Massimo), Dourado, M.R. (Mauricio R), Driedonks, T.A.P. (Tom AP), Duarte, F.V. (Filipe V), Duncan, H.M. (Heather M), Eichenberger, R.M. (Ramon M), Ekström, K. (Karin), EL Andaloussi, S. (Samir), Elie-Caille, C. (Celine), Erdbrügger, U. (Uta), Falcon-Perez, J.M. (Juan), Fatima, F. (Farah), Fish, J.E. (Jason E), Flores-Bellver, M. (Miguel), Försönits, A. (András), Frelet-Barrand, A. (Annie), Fricke, F. (Fabia), Fuhrmann, G. (Gregor), Gabrielsson, S. (Susanne), Gámez-Valero, A. (Ana), Gardiner, C. (Chris), Gärtner, K. (Kathrin), Gaudin, R. (Raphael), Gho, Y.S. (Yong Song), Giebel, B. (B.), Gilbert, C. (Caroline), Gimona, M. (Mario), Giusti, I. (Ilaria), Goberdhan, D.C.I. (Deborah CI), Görgens, A. (André), Gorski, S.M. (Sharon M), Greening, D.W. (David W.), Gross, J.C. (Julia Christina), Gualerzi, A. (Alice), Gupta, G.N. (Gopal N), Gustafson, D. (Dakota), Handberg, A. (Aase), Haraszti, R.A. (Reka A), Harrison, P. (Paul), Hegyesi, H. (Hargita), Hendrix, A. (An), Hill, A.F. (Andrew F), Hochberg, F.H. (Fred H), Hoffmann, K.F. (Karl F), Holder, B. (Beth), Holthofer, H. (Harry), Hosseinkhani, B. (Baharak), Hu, G. (Guoku), Huang, Y. (Yiyao), Huber, V. (Veronica), Hunt, S. (Stuart), Ibrahim, A.G.-E. (Ahmed Gamal-Eldin), Ikezu, T. (Tsuneya), Inal, J.M. (Jameel), Isin, M. (Mustafa), Ivanova, A. (Alena), Jackson, H.K. (Hannah K), Jacobsen, S. (Soren), Jay, S.M. (Steven M), Jayachandran, M. (Muthuvel), Jenster, G.W. (Guido), Jiang, L. (Lanzhou), Johnson, S.M. (Suzanne M), Jones, J.C. (Jennifer C), Jong, A. (Ambrose), Jovanovic-Talisman, T. (Tijana), Jung, S. (Stephanie), Kalluri, R. (Raghu), Kano, S.-I. (Shin-ichi), Kaur, S. (Sukhbir), Kawamura, Y. (Yumi), Keller, E.T. (Evan T), Khamari, D. (Delaram), Khomyakova, E. (Elena), Khvorova, A. (Anastasia), Kierulf, P. (Peter), Kim, K.P. (Kwang Pyo), Kislinger, T. (Thomas), Klingeborn, M. (Mikael), Klinke, D.J. (David J), Kornek, M. (Miroslaw), Kosanović, M.M. (Maja M), Kovács, Á.F. (Árpád Ferenc), Krämer-Albers, E.-M. (Eva-Maria), Krasemann, S. (Susanne), Krause, M. (Mirja), Kurochkin, I.V. (Igor V), Kusuma, G.D. (Gina D), Kuypers, S. (Sören), Laitinen, S. (Saara), Langevin, S.M. (Scott M), Languino, L.R. (Lucia R), Lannigan, J. (Joanne), Lässer, C. (Cecilia), Laurent, L.C. (Louise C), Lavieu, G. (Gregory), Lázaro-Ibáñez, E. (Elisa), Le Lay, S. (Soazig), Lee, M.-S. (Myung-Shin), Lee, Y.X.F. (Yi Xin Fiona), Lemos, D.S. (Debora S), Lenassi, M. (Metka), Leszczynska, A. (Aleksandra), Li, I.T.S. (Isaac TS), Liao, K. (Ke), Libregts, S.F. (Sten), Ligeti, E. (Erzsebet), Lim, R. (Rebecca), Lim, S.K. (Sai Kiang), Linē, A. (Aija), Linnemannstöns, K. (Karen), Llorente, A. (Alicia), Lombard, C.A. (Catherine A), Lorenowicz, M.J. (Magdalena J), Lörincz, Á.M. (Ákos M), Lötvall, J. (Jan), Lovett, J. (Jason), Lowry, M.C. (Michelle C), Loyer, X. (Xavier), Lu, Q. (Quan), Lukomska, B. (Barbara), Lunavat, T.R. (Taral R), Maas, S.L.N. (Sybren), Malhi, H. (Harmeet), Marcilla, A. (Antonio), Mariani, J. (Jacopo), Mariscal, J. (Javier), Martens-Uzunova, E.S. (Elena), Martin-Jaular, L. (Lorena), Martinez, M.C. (M Carmen), Martins, V.R. (Vilma Regina), Mathieu, M. (Mathilde), Mathivanan, S. (Suresh), Maugeri, M. (Marco), McGinnis, L.K. (Lynda K), McVey, M.J. (Mark J), Meckes, D.G. (David G), Meehan, K.L. (Katie L), Mertens, I. (Inge), Minciacchi, V.R. (Valentina R), Möller, A. (Andreas), Møller Jørgensen, M. (Malene), Morales-Kastresana, A. (Aizea), Morhayim, J. (Jess), Mullier, F. (Francois), Muraca, M. (Maurizio), Musante, L. (Luca), Mussack, V. (Veronika), Muth, D.C. (Dillon C), Myburgh, K.H. (Kathryn H), Najrana, T. (Tanbir), Nawaz, M. (Muhammad), Nazarenko, I. (Irina), Nejsum, P. (Peter), Neri, C. (Christian), Neri, T. (Tommaso), Nieuwland, C.C.M. (Carolien) van, Nimrichter, L. (Leonardo), Nolan, J.P. (John P), Nolte-’t Hoen, E.N.M. (Esther NM), Hooten, N.N. (Nicole Noren), O’Driscoll, L. (Lorraine), O’Grady, T. (Tina), O’Loghlen, A. (Ana), Ochiya, T. (Takahiro), Olivier, M. (Martin), Ortiz, A. (Alberto), Ortiz, L.A. (Luis A), Osteikoetxea, X. (Xabier), Ostegaard, O. (Ole), Ostrowski, M. (Matias), Park, J. (Jaesung), Pegtel, D.M. (D. Michiel), Peinado, H. (Hector), Perut, F. (Francesca), Pfaffl, M.W. (Michael W), Phinney, D.G. (Donald G), Pieters, B.C.H. (Bartijn CH), Pink, R.C. (Ryan C), Pisetsky, D.S. (David S), Pogge von Strandmann, E. (Elke), Polakovicova, I. (Iva), Poon, I.K.H. (Ivan KH), Powell, B.H. (Bonita H), Prada, I. (Ilaria), Pulliam, L. (Lynn), Quesenberry, P. (Peter), Radeghieri, A. (Annalisa), Raffai, R.L. (Robert L), Raimondo, S. (Stefania), Rak, J. (Janusz), Ramirez, M.I. (Marcel I.), Raposo, L. (Luís), Rayyan, M.S. (Morsi S), Regev-Rudzki, N. (Neta), Ricklefs, F.L. (Franz L), Robbins, P.D. (Paul D), Roberts, D.D. (David D), Rodrigues, S.C. (Silvia C), Rohde, E. (Eva), Rome, S. (Sophie), Rouschop, K.M.A. (Kasper MA), Rughetti, A. (Aurelia), Russell, A.E. (Ashley E), Saá, P. (Paula), Sahoo, S. (Susmita), Salas-Huenuleo, E. (Edison), Sánchez, C. (Catherine), Saugstad, J.A. (Julie A), Saul, M.J. (Meike J), Schiffelers, R.M. (Raymond), Schneider, R. (Raphael), Schøyen, T.H. (Tine Hiorth), Scott, A. (Aaron), Shahaj, E. (Eriomina), Sharma, S. (Shivani), Shatnyeva, O. (Olga), Shekari, F. (Faezeh), Shelke, G.V. (Ganesh Vilas), Shetty, A.K. (Ashok K), Shiba, K. (Kiyotaka), Siljander, P. (Pia), Silva, A.M. (Andreia M), Skowronek, A. (Agata), Snyder, O.L. (Orman L), Soares, R.P. (Rodrigo Pedro), Sódar, B.W. (Barbara W), Soekmadji, C. (Carolina), Sotillo, J. (Javier), Stahl, P.D. (Philip D), Stoorvogel, W. (Willem), Stott, S.L. (Shannon L), Strasser, E.F. (Erwin F), Swift, S. (Simon), Tahara, H. (Hidetoshi), Tewari, M. (Muneesh), Timms, K. (Kate), Tiwari, S. (Swasti), Tixeira, R. (Rochelle), Tkach, M. (Mercedes), Toh, W.S. (Wei Seong), Tomasini, R. (Richard), Torrecilhas, A.C. (Ana Claudia), Tosar, J.P. (Juan Pablo), Toxavidis, V. (Vasilis), Urbanelli, L. (Lorena), Vader, P. (Pieter), Balkom, B.W.M. (Bas) van, van der Grein, S.G. (Susanne G), Van Deun, J. (Jan), van Herwijnen, M.J.C. (Martijn JC), Van Keuren-Jensen, K. (Kendall), van Niel, G. (Guillaume), Royen, M.E. (Martin), van Wijnen, A.J. (Andre J), Vasconcelos, M.H. (M Helena), Vechetti, I.J. (Ivan J), Veit, T.D. (Tiago D), Vella, L.J. (Laura J.), Velot, É. (Émilie), Verweij, F.J. (Frederik J), Vestad, B. (Beate), Viñas, J.L. (Jose L), Visnovitz, T. (Tamás), Vukman, K.V. (Krisztina V), Wahlgren, J. (Jessica), Watson, D.C. (Dionysios C), Wauben, M.H.M. (Marca), Weaver, A. (Alissa), Webber, J.P. (Jason P), Weber, V. (Viktoria), Wehman, A.M. (Ann M), Weiss, D.J. (Daniel J), Welsh, J.A. (Joshua A), Wendt, S. (Sebastian), Wheelock, A.M. (Asa M), Wiener, Z. (Zoltán), Witte, L. (Leonie), Wolfram, J. (Joy), Xagorari, A. (Angeliki), Xander, P. (Patricia), Xu, J. (Jing), Yan, X. (Xiaomei), Yáñez-Mó, M. (María), Yin, H. (Hang), Yuana, Y., Zappulli, V. (Valentina), Zarubova, J. (Jana), Žėkas, V. (Vytautas), Zhang, J.-Y. (Jian-ye), Zhao, Z. (Zezhou), Zheng, L. (Lei), Zheutlin, A.R. (Alexander R), Zickler, A.M. (Antje M), Zimmermann, P. (Pascale), Zivkovic, A.M. (Angela M), Zocco, D. (Davide), Zuba-Surma, E.K. (Ewa K), Thery, C., Witwer, K. (Kenneth), Aikawa, E. (Elena), Alcaraz, M.J. (Maria Jose), Anderson, J.D. (Johnathon D), Andriantsitohaina, R. (Ramaroson), Antoniou, A. (Anna), Arab, T. (Tanina), Archer, F. (Fabienne), Atkin-Smith, G.K. (Georgia K), Ayre, D.C. (D Craig), Bach, J.-M. (Jean-Marie), Bachurski, D. (Daniel), Baharvand, H. (Hossein), Balaj, L. (Leonora), Baldacchino, S. (Shawn), Bauer, N.N. (Natalie N), Baxter, A.A. (Amy A), Bebawy, M. (Mary), Beckham, C. (Carla), Bedina Zavec, A. (Apolonija), Benmoussa, A. (Abderrahim), Berardi, A.C. (Anna C), Bergese, P. (Paolo), Bielska, E. (Ewa), Blenkiron, C. (Cherie), Bobis-Wozowicz, S. (Sylwia), Boilard, E. (Eric), Boireau, W. (Wilfrid), Bongiovanni, A. (Antonella), Borràs, F.E. (Francesc), Bosch, S. (Steffi), Boulanger, C.M. (Chantal), Breakefield, X. (Xandra), Breglio, A.M. (Andrew M), Brennan, M.Á. (Meadhbh Á), Brigstock, D.R. (David R), Brisson, A. (Alain), Broekman, M.L.D. (Marike), Bromberg, J.F. (Jacqueline F), Bryl-Górecka, P. (Paulina), Buch, S. (Shilpa), Buck, A.H. (Amy H), Burger, D. (Dylan), Busatto, S. (Sara), Buschmann, D. (Dominik), Bussolati, B. (Benedetta), Buzas, E. (Edit), Byrd, J.B. (James Bryan), Camussi, G. (Giovanni), Carter, D.R.F. (David RF), Caruso, S. (Sarah), Chamley, L.W. (Lawrence W), Chang, Y.-T. (Yu-Ting), Chaudhuri, A.D. (Amrita Datta), Chen, C. (Chihchen), Chen, S. (Shuai), Cheng, L. (Lesley), Chin, A.R. (Andrew R), Clayton, A. (Aled), Clerici, S.P. (Stefano P), Cocks, A. (Alex), Cocucci, E. (Emanuele), Coffey, R.J. (Robert J), Cordeiro-da-Silva, A. (Anabela), Couch, Y. (Yvonne), Coumans, F.A.W. (Frank AW), Coyle, B. (Beth), Crescitelli, R. (Rossella), Criado, M.F. (Miria Ferreira), D’Souza-Schorey, C. (Crislyn), Das, S. (Saumya), de Candia, P. (Paola), De Santana, E.F. (Eliezer F), De Wever, O. (Olivier), Del Portillo, H. (Hernando), Demaret, T. (Tanguy), Deville, S. (Sarah), Devitt, A. (Andrew), Dhondt, B. (Bert), Di Vizio, D. (Dolores), Dieterich, L.C. (Lothar C), Dolo, V. (Vincenza), Dominguez Rubio, A.P. (Ana Paula), Dominici, M. (Massimo), Dourado, M.R. (Mauricio R), Driedonks, T.A.P. (Tom AP), Duarte, F.V. (Filipe V), Duncan, H.M. (Heather M), Eichenberger, R.M. (Ramon M), Ekström, K. (Karin), EL Andaloussi, S. (Samir), Elie-Caille, C. (Celine), Erdbrügger, U. (Uta), Falcon-Perez, J.M. (Juan), Fatima, F. (Farah), Fish, J.E. (Jason E), Flores-Bellver, M. (Miguel), Försönits, A. (András), Frelet-Barrand, A. (Annie), Fricke, F. (Fabia), Fuhrmann, G. (Gregor), Gabrielsson, S. (Susanne), Gámez-Valero, A. (Ana), Gardiner, C. (Chris), Gärtner, K. (Kathrin), Gaudin, R. (Raphael), Gho, Y.S. (Yong Song), Giebel, B. (B.), Gilbert, C. (Caroline), Gimona, M. (Mario), Giusti, I. (Ilaria), Goberdhan, D.C.I. (Deborah CI), Görgens, A. (André), Gorski, S.M. (Sharon M), Greening, D.W. (David W.), Gross, J.C. (Julia Christina), Gualerzi, A. (Alice), Gupta, G.N. (Gopal N), Gustafson, D. (Dakota), Handberg, A. (Aase), Haraszti, R.A. (Reka A), Harrison, P. (Paul), Hegyesi, H. (Hargita), Hendrix, A. (An), Hill, A.F. (Andrew F), Hochberg, F.H. (Fred H), Hoffmann, K.F. (Karl F), Holder, B. (Beth), Holthofer, H. (Harry), Hosseinkhani, B. (Baharak), Hu, G. (Guoku), Huang, Y. (Yiyao), Huber, V. (Veronica), Hunt, S. (Stuart), Ibrahim, A.G.-E. (Ahmed Gamal-Eldin), Ikezu, T. (Tsuneya), Inal, J.M. (Jameel), Isin, M. (Mustafa), Ivanova, A. (Alena), Jackson, H.K. (Hannah K), Jacobsen, S. (Soren), Jay, S.M. (Steven M), Jayachandran, M. (Muthuvel), Jenster, G.W. (Guido), Jiang, L. (Lanzhou), Johnson, S.M. (Suzanne M), Jones, J.C. (Jennifer C), Jong, A. (Ambrose), Jovanovic-Talisman, T. (Tijana), Jung, S. (Stephanie), Kalluri, R. (Raghu), Kano, S.-I. (Shin-ichi), Kaur, S. (Sukhbir), Kawamura, Y. (Yumi), Keller, E.T. (Evan T), Khamari, D. (Delaram), Khomyakova, E. (Elena), Khvorova, A. (Anastasia), Kierulf, P. (Peter), Kim, K.P. (Kwang Pyo), Kislinger, T. (Thomas), Klingeborn, M. (Mikael), Klinke, D.J. (David J), Kornek, M. (Miroslaw), Kosanović, M.M. (Maja M), Kovács, Á.F. (Árpád Ferenc), Krämer-Albers, E.-M. (Eva-Maria), Krasemann, S. (Susanne), Krause, M. (Mirja), Kurochkin, I.V. (Igor V), Kusuma, G.D. (Gina D), Kuypers, S. (Sören), Laitinen, S. (Saara), Langevin, S.M. (Scott M), Languino, L.R. (Lucia R), Lannigan, J. (Joanne), Lässer, C. (Cecilia), Laurent, L.C. (Louise C), Lavieu, G. (Gregory), Lázaro-Ibáñez, E. (Elisa), Le Lay, S. (Soazig), Lee, M.-S. (Myung-Shin), Lee, Y.X.F. (Yi Xin Fiona), Lemos, D.S. (Debora S), Lenassi, M. (Metka), Leszczynska, A. (Aleksandra), Li, I.T.S. (Isaac TS), Liao, K. (Ke), Libregts, S.F. (Sten), Ligeti, E. (Erzsebet), Lim, R. (Rebecca), Lim, S.K. (Sai Kiang), Linē, A. (Aija), Linnemannstöns, K. (Karen), Llorente, A. (Alicia), Lombard, C.A. (Catherine A), Lorenowicz, M.J. (Magdalena J), Lörincz, Á.M. (Ákos M), Lötvall, J. (Jan), Lovett, J. (Jason), Lowry, M.C. (Michelle C), Loyer, X. (Xavier), Lu, Q. (Quan), Lukomska, B. (Barbara), Lunavat, T.R. (Taral R), Maas, S.L.N. (Sybren), Malhi, H. (Harmeet), Marcilla, A. (Antonio), Mariani, J. (Jacopo), Mariscal, J. (Javier), Martens-Uzunova, E.S. (Elena), Martin-Jaular, L. (Lorena), Martinez, M.C. (M Carmen), Martins, V.R. (Vilma Regina), Mathieu, M. (Mathilde), Mathivanan, S. (Suresh), Maugeri, M. (Marco), McGinnis, L.K. (Lynda K), McVey, M.J. (Mark J), Meckes, D.G. (David G), Meehan, K.L. (Katie L), Mertens, I. (Inge), Minciacchi, V.R. (Valentina R), Möller, A. (Andreas), Møller Jørgensen, M. (Malene), Morales-Kastresana, A. (Aizea), Morhayim, J. (Jess), Mullier, F. (Francois), Muraca, M. (Maurizio), Musante, L. (Luca), Mussack, V. (Veronika), Muth, D.C. (Dillon C), Myburgh, K.H. (Kathryn H), Najrana, T. (Tanbir), Nawaz, M. (Muhammad), Nazarenko, I. (Irina), Nejsum, P. (Peter), Neri, C. (Christian), Neri, T. (Tommaso), Nieuwland, C.C.M. (Carolien) van, Nimrichter, L. (Leonardo), Nolan, J.P. (John P), Nolte-’t Hoen, E.N.M. (Esther NM), Hooten, N.N. (Nicole Noren), O’Driscoll, L. (Lorraine), O’Grady, T. (Tina), O’Loghlen, A. (Ana), Ochiya, T. (Takahiro), Olivier, M. (Martin), Ortiz, A. (Alberto), Ortiz, L.A. (Luis A), Osteikoetxea, X. (Xabier), Ostegaard, O. (Ole), Ostrowski, M. (Matias), Park, J. (Jaesung), Pegtel, D.M. (D. Michiel), Peinado, H. (Hector), Perut, F. (Francesca), Pfaffl, M.W. (Michael W), Phinney, D.G. (Donald G), Pieters, B.C.H. (Bartijn CH), Pink, R.C. (Ryan C), Pisetsky, D.S. (David S), Pogge von Strandmann, E. (Elke), Polakovicova, I. (Iva), Poon, I.K.H. (Ivan KH), Powell, B.H. (Bonita H), Prada, I. (Ilaria), Pulliam, L. (Lynn), Quesenberry, P. (Peter), Radeghieri, A. (Annalisa), Raffai, R.L. (Robert L), Raimondo, S. (Stefania), Rak, J. (Janusz), Ramirez, M.I. (Marcel I.), Raposo, L. (Luís), Rayyan, M.S. (Morsi S), Regev-Rudzki, N. (Neta), Ricklefs, F.L. (Franz L), Robbins, P.D. (Paul D), Roberts, D.D. (David D), Rodrigues, S.C. (Silvia C), Rohde, E. (Eva), Rome, S. (Sophie), Rouschop, K.M.A. (Kasper MA), Rughetti, A. (Aurelia), Russell, A.E. (Ashley E), Saá, P. (Paula), Sahoo, S. (Susmita), Salas-Huenuleo, E. (Edison), Sánchez, C. (Catherine), Saugstad, J.A. (Julie A), Saul, M.J. (Meike J), Schiffelers, R.M. (Raymond), Schneider, R. (Raphael), Schøyen, T.H. (Tine Hiorth), Scott, A. (Aaron), Shahaj, E. (Eriomina), Sharma, S. (Shivani), Shatnyeva, O. (Olga), Shekari, F. (Faezeh), Shelke, G.V. (Ganesh Vilas), Shetty, A.K. (Ashok K), Shiba, K. (Kiyotaka), Siljander, P. (Pia), Silva, A.M. (Andreia M), Skowronek, A. (Agata), Snyder, O.L. (Orman L), Soares, R.P. (Rodrigo Pedro), Sódar, B.W. (Barbara W), Soekmadji, C. (Carolina), Sotillo, J. (Javier), Stahl, P.D. (Philip D), Stoorvogel, W. (Willem), Stott, S.L. (Shannon L), Strasser, E.F. (Erwin F), Swift, S. (Simon), Tahara, H. (Hidetoshi), Tewari, M. (Muneesh), Timms, K. (Kate), Tiwari, S. (Swasti), Tixeira, R. (Rochelle), Tkach, M. (Mercedes), Toh, W.S. (Wei Seong), Tomasini, R. (Richard), Torrecilhas, A.C. (Ana Claudia), Tosar, J.P. (Juan Pablo), Toxavidis, V. (Vasilis), Urbanelli, L. (Lorena), Vader, P. (Pieter), Balkom, B.W.M. (Bas) van, van der Grein, S.G. (Susanne G), Van Deun, J. (Jan), van Herwijnen, M.J.C. (Martijn JC), Van Keuren-Jensen, K. (Kendall), van Niel, G. (Guillaume), Royen, M.E. (Martin), van Wijnen, A.J. (Andre J), Vasconcelos, M.H. (M Helena), Vechetti, I.J. (Ivan J), Veit, T.D. (Tiago D), Vella, L.J. (Laura J.), Velot, É. (Émilie), Verweij, F.J. (Frederik J), Vestad, B. (Beate), Viñas, J.L. (Jose L), Visnovitz, T. (Tamás), Vukman, K.V. (Krisztina V), Wahlgren, J. (Jessica), Watson, D.C. (Dionysios C), Wauben, M.H.M. (Marca), Weaver, A. (Alissa), Webber, J.P. (Jason P), Weber, V. (Viktoria), Wehman, A.M. (Ann M), Weiss, D.J. (Daniel J), Welsh, J.A. (Joshua A), Wendt, S. (Sebastian), Wheelock, A.M. (Asa M), Wiener, Z. (Zoltán), Witte, L. (Leonie), Wolfram, J. (Joy), Xagorari, A. (Angeliki), Xander, P. (Patricia), Xu, J. (Jing), Yan, X. (Xiaomei), Yáñez-Mó, M. (María), Yin, H. (Hang), Yuana, Y., Zappulli, V. (Valentina), Zarubova, J. (Jana), Žėkas, V. (Vytautas), Zhang, J.-Y. (Jian-ye), Zhao, Z. (Zezhou), Zheng, L. (Lei), Zheutlin, A.R. (Alexander R), Zickler, A.M. (Antje M), Zimmermann, P. (Pascale), Zivkovic, A.M. (Angela M), Zocco, D. (Davide), and Zuba-Surma, E.K. (Ewa K)

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 the

Published
2019
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13. Comprehensive RNA-sequencing analysis in serum and muscle reveals novel small RNA signatures with biomarker potential for DMD

Author

Coenen-Stass, AML, Sork, H, Gatto, S, Godfrey, C, Bhomra, A, Krjutškov, K, Hart, JR, Westholm, JO, O'Donovan, L, Roos, A, Lochmüller, H, Puri, PL, El Andaloussi, S, Wood, MJA, and Roberts, TC

Subjects
musculoskeletal diseases, Duchenne muscular dystrophy, congenital, hereditary, and neonatal diseases and abnormalities, lcsh:Therapeutics. Pharmacology, microRNA, lcsh:RM1-950, piRNA, Small RNA sequencing, Extracellular miRNA
Abstract

Extracellular small RNAs (sRNAs), including microRNAs (miRNAs), are promising biomarkers for diseases such as Duchenne muscular dystrophy (DMD), although their biological relevance is largely unknown. To investigate the relationship between intracellular and extracellular sRNA levels on a global scale, we performed sRNA sequencing in four muscle types and serum from wild-type, dystrophic mdx, and mdx mice in which dystrophin protein expression was restored by exon skipping. Differentially abundant sRNAs were identified in serum (mapping to miRNA, small nuclear RNA [snRNA], and PIWI-interacting RNA [piRNA] loci). One novel candidate biomarker, miR-483, was increased in both mdx serum and muscle, and also elevated in DMD patient sera. Dystrophin restoration induced global shifts in miRNA (including miR-483) and snRNA-fragment abundance toward wild-type levels. Specific serum piRNA-like sRNAs also responded to exon skipping therapy. Absolute miRNA expression in muscle was positively correlated with abundance in the circulation, although multiple highly expressed miRNAs in muscle were not elevated in mdx serum, suggesting that both passive and selective release mechanisms contribute to serum miRNA levels. In conclusion, this study has revealed new insights into the sRNA biology of dystrophin deficiency and identified novel DMD biomarkers. Keywords: small RNA sequencing, microRNA, piRNA, Duchenne muscular dystrophy, extracellular miRNA

Published
2018

14. Single-Stranded Nucleic Acids Regulate TLR3/4/7 Activation through Interference with Clathrin-Mediated Endocytosis

Author

Järver, P., Dondalska, A., Poux, C., Sandberg, A. S., Bergenstråhle, Joseph, Sköld, A. E., Dereuddre-Bosquet, N., Martinon, F., Pålsson, S., Zaghloul, E., Brodin, D., Sander, B., Lennox, K. A., Behlke, M. A., EL-Andaloussi, S., Lehtiö, J., Lundeberg, Joakim, LeGrand, R., Spetz, A. -L, Järver, P., Dondalska, A., Poux, C., Sandberg, A. S., Bergenstråhle, Joseph, Sköld, A. E., Dereuddre-Bosquet, N., Martinon, F., Pålsson, S., Zaghloul, E., Brodin, D., Sander, B., Lennox, K. A., Behlke, M. A., EL-Andaloussi, S., Lehtiö, J., Lundeberg, Joakim, LeGrand, R., and Spetz, A. -L

Abstract

Recognition of nucleic acids by endosomal Toll-like receptors (TLR) is essential to combat pathogens, but requires strict control to limit inflammatory responses. The mechanisms governing this tight regulation are unclear. We found that single-stranded oligonucleotides (ssON) inhibit endocytic pathways used by cargo destined for TLR3/4/7 signaling endosomes. Both ssDNA and ssRNA conferred the endocytic inhibition, it was concentration dependent, and required a certain ssON length. The ssON-mediated inhibition modulated signaling downstream of TLRs that localized within the affected endosomal pathway. We further show that injection of ssON dampens dsRNA-mediated inflammatory responses in the skin of non-human primates. These studies reveal a regulatory role for extracellular ssON in the endocytic uptake of TLR ligands and provide a mechanistic explanation of their immunomodulation. The identified ssON-mediated interference of endocytosis (SOMIE) is a regulatory process that temporarily dampens TLR3/4/7 signaling, thereby averting excessive immune responses., QC 20190626

Published
2018
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15. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

Author

Théry, C, Witwer, KW, Aikawa, E, Alcaraz, MJ, Anderson, JD, Andriantsitohaina, R, Antoniou, A, Arab, T, Archer, F, Atkin-Smith, GK, Ayre, DC, Bach, JM, Bachurski, D, Baharvand, H, Balaj, L, Baldacchino, S, Bauer, NN, Baxter, AA, Bebawy, M, Beckham, C, Bedina Zavec, A, Benmoussa, A, Berardi, AC, Bergese, P, Bielska, E, Blenkiron, C, Bobis-Wozowicz, S, Boilard, E, Boireau, W, Bongiovanni, A, Borràs, FE, Bosch, S, Boulanger, CM, Breakefield, X, Breglio, AM, Brennan, M, Brigstock, DR, Brisson, A, Broekman, MLD, Bromberg, JF, Bryl-Górecka, P, Buch, S, Buck, AH, Burger, D, Busatto, S, Buschmann, D, Bussolati, B, Buzás, EI, Byrd, JB, Camussi, G, Carter, DRF, Caruso, S, Chamley, LW, Chang, YT, Chaudhuri, AD, Chen, C, Chen, S, Cheng, L, Chin, AR, Clayton, A, Clerici, SP, Cocks, A, Cocucci, E, Coffey, RJ, Cordeiro-da-Silva, A, Couch, Y, Coumans, FAW, Coyle, B, Crescitelli, R, Criado, MF, D’Souza-Schorey, C, Das, S, de Candia, P, De Santana, EF, De Wever, O, del Portillo, HA, Demaret, T, Deville, S, Devitt, A, Dhondt, B, Di Vizio, D, Dieterich, LC, Dolo, V, Dominguez Rubio, AP, Dominici, M, Dourado, MR, Driedonks, TAP, Duarte, FV, Duncan, HM, Eichenberger, RM, Ekström, K, EL Andaloussi, S, Elie-Caille, C, Erdbrügger, U, Falcón-Pérez, JM, Fatima, F, Fish, JE, Flores-Bellver, M, Försönits, A, Frelet-Barrand, A, Théry, C, Witwer, KW, Aikawa, E, Alcaraz, MJ, Anderson, JD, Andriantsitohaina, R, Antoniou, A, Arab, T, Archer, F, Atkin-Smith, GK, Ayre, DC, Bach, JM, Bachurski, D, Baharvand, H, Balaj, L, Baldacchino, S, Bauer, NN, Baxter, AA, Bebawy, M, Beckham, C, Bedina Zavec, A, Benmoussa, A, Berardi, AC, Bergese, P, Bielska, E, Blenkiron, C, Bobis-Wozowicz, S, Boilard, E, Boireau, W, Bongiovanni, A, Borràs, FE, Bosch, S, Boulanger, CM, Breakefield, X, Breglio, AM, Brennan, M, Brigstock, DR, Brisson, A, Broekman, MLD, Bromberg, JF, Bryl-Górecka, P, Buch, S, Buck, AH, Burger, D, Busatto, S, Buschmann, D, Bussolati, B, Buzás, EI, Byrd, JB, Camussi, G, Carter, DRF, Caruso, S, Chamley, LW, Chang, YT, Chaudhuri, AD, Chen, C, Chen, S, Cheng, L, Chin, AR, Clayton, A, Clerici, SP, Cocks, A, Cocucci, E, Coffey, RJ, Cordeiro-da-Silva, A, Couch, Y, Coumans, FAW, Coyle, B, Crescitelli, R, Criado, MF, D’Souza-Schorey, C, Das, S, de Candia, P, De Santana, EF, De Wever, O, del Portillo, HA, Demaret, T, Deville, S, Devitt, A, Dhondt, B, Di Vizio, D, Dieterich, LC, Dolo, V, Dominguez Rubio, AP, Dominici, M, Dourado, MR, Driedonks, TAP, Duarte, FV, Duncan, HM, Eichenberger, RM, Ekström, K, EL Andaloussi, S, Elie-Caille, C, Erdbrügger, U, Falcón-Pérez, JM, Fatima, F, Fish, JE, Flores-Bellver, M, Försönits, A, and Frelet-Barrand, A

Abstract

© 2018, © 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group on behalf of The International Society for Extracellular Vesicles. 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.

Published
2018

17. Cells release subpopulations of exosomes with distinct molecular and biological properties

Author

Willms, E, Johansson, H, Mäger, I, Lee, Y, Blomberg, K, Sadik, M, Alaarg, A, Smith, C, Lehtiö, J, El Andaloussi, S, Wood, M, Vader, P, Faculty of Science and Technology, Biomaterials Science and Technology, Sub General Pharmaceutics, and Pharmaceutics

Subjects
Mice, Cell Line, Tumor, Research Support, Non-U.S. Gov't, Melanoma, Experimental, Journal Article, Animals, Exosomes, Article
Abstract

Cells release nano-sized membrane vesicles that are involved in intercellular communication by transferring biological information between cells. It is generally accepted that cells release at least three types of extracellular vesicles (EVs): apoptotic bodies, microvesicles and exosomes. While a wide range of putative biological functions have been attributed to exosomes, they are assumed to represent a homogenous population of EVs. We hypothesized the existence of subpopulations of exosomes with defined molecular compositions and biological properties. Density gradient centrifugation of isolated exosomes revealed the presence of two distinct subpopulations, differing in biophysical properties and their proteomic and RNA repertoires. Interestingly, the subpopulations mediated differential effects on the gene expression programmes in recipient cells. In conclusion, we demonstrate that cells release distinct exosome subpopulations with unique compositions that elicit differential effects on recipient cells. Further dissection of exosome heterogeneity will advance our understanding of exosomal biology in health and disease and accelerate the development of exosome-based diagnostics and therapeutics.

Published
2016

18. Comparative high resolution proteomic analysis of dystrophic mouse models reveals a core dystrophic proteome and the impact of aging

Author

van Westering, T., primary, Johansson, H., additional, Coenen-Stass, A., additional, Miyatake, S., additional, Tanihata, J., additional, Takeda, S., additional, Yokota, T., additional, Lehtiö, J., additional, Wood, M., additional, El Andaloussi, S., additional, Roberts, T., additional, and Aoki, Y., additional

Published
2017
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20. C9ORF72 and RAB7L1 regulate vesicle traffi cking in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia

Author

Manzano, R., primary, Aoki, Y., additional, Lee, Y., additional, Dafinca, R., additional, Aoki, M., additional, Douglas, A.G.L., additional, Varela, M.A., additional, Sathyaprakash, C., additional, Scaber, J., additional, Barbagallo, P., additional, Vader, P., additional, Mäger, I., additional, Ezzat, K., additional, Turner, M.R., additional, Ito, N., additional, Gasco, S., additional, Ohbayashi, N., additional, El Andaloussi, S., additional, Taked, S., additional, Fukuda, M., additional, Talbot, K., additional, and Wood, M.J.A., additional

Published
2017
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21. In Vivo Effects of Mesenchymal Stromal Cells in Two Patients With Severe Acute Respiratory Distress Syndrome.

Author

Simonson, OE, Mougiakakos, D, Heldring, N, Bassi, G, Johansson, HJ, Dalén, M, Jitschin, R, Rodin, S, Corbascio, M, El Andaloussi, S, Wiklander, OPB, Nordin, JZ, Skog, J, Romain, C, Koestler, T, Hellgren-Johansson, L, Schiller, P, Joachimsson, P-O, Hägglund, H, Mattsson, M, Lehtiö, J, Faridani, OR, Sandberg, R, Korsgren, O, Krampera, M, Weiss, DJ, Grinnemo, K-H, Le Blanc, K, Simonson, OE, Mougiakakos, D, Heldring, N, Bassi, G, Johansson, HJ, Dalén, M, Jitschin, R, Rodin, S, Corbascio, M, El Andaloussi, S, Wiklander, OPB, Nordin, JZ, Skog, J, Romain, C, Koestler, T, Hellgren-Johansson, L, Schiller, P, Joachimsson, P-O, Hägglund, H, Mattsson, M, Lehtiö, J, Faridani, OR, Sandberg, R, Korsgren, O, Krampera, M, Weiss, DJ, Grinnemo, K-H, and Le Blanc, K

Published
2016

22. Applying extracellular vesicles based therapeutics in clinical trials - an ISEV position paper

Author

Lener, T, Gimona, M, Aigner, L, Boerger, V, Buzas, E, Camussi, G, Chaput, N, Chatterjee, D, Court, FA, del Portillo, HA, O'Driscoll, L, Fais, S, Falcon-Perez, JM, Felderhoff-Mueser, U, Fraile, L, Gho, YS, Goergens, A, Gupta, RC, Hendrix, A, Hermann, DM, Hill, AF, Hochberg, F, Horn, PA, de Kleijn, D, Kordelas, L, Kramer, BW, Kraemer-Albers, E-M, Laner-Plamberger, S, Laitinen, S, Leonardi, T, Lorenowicz, MJ, Lim, SK, Lotvall, J, Maguire, CA, Marcilla, A, Nazarenko, I, Ochiya, T, Patel, T, Pedersen, S, Pocsfalvi, G, Pluchino, S, Quesenberry, P, Reischl, IG, Rivera, FJ, Sanzenbacher, R, Schallmoser, K, Slaper-Cortenbach, I, Strunk, D, Tonn, T, Vader, P, van Balkom, BWM, Wauben, M, El Andaloussi, S, Thery, C, Rohde, E, Giebel, B, Lener, T, Gimona, M, Aigner, L, Boerger, V, Buzas, E, Camussi, G, Chaput, N, Chatterjee, D, Court, FA, del Portillo, HA, O'Driscoll, L, Fais, S, Falcon-Perez, JM, Felderhoff-Mueser, U, Fraile, L, Gho, YS, Goergens, A, Gupta, RC, Hendrix, A, Hermann, DM, Hill, AF, Hochberg, F, Horn, PA, de Kleijn, D, Kordelas, L, Kramer, BW, Kraemer-Albers, E-M, Laner-Plamberger, S, Laitinen, S, Leonardi, T, Lorenowicz, MJ, Lim, SK, Lotvall, J, Maguire, CA, Marcilla, A, Nazarenko, I, Ochiya, T, Patel, T, Pedersen, S, Pocsfalvi, G, Pluchino, S, Quesenberry, P, Reischl, IG, Rivera, FJ, Sanzenbacher, R, Schallmoser, K, Slaper-Cortenbach, I, Strunk, D, Tonn, T, Vader, P, van Balkom, BWM, Wauben, M, El Andaloussi, S, Thery, C, Rohde, E, and Giebel, B

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.

Published
2015

23. The physiological consequences of different levels of dystrophin following antisense based exon-skipping in the mdx mouse

Author

Muses, S., primary, Godfrey, C., additional, McClorey, G., additional, Wells, K., additional, Coursindel, T., additional, Terry, R., additional, Betts, C, additional, Cappellari, O., additional, Hammond, S., additional, O'Donovan, E., additional, Hildyard, J., additional, El Andaloussi, S., additional, Gait, M., additional, Wood, M., additional, and Wells, D., additional

Published
2015
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24. Intratracheale Anwendung von autologen Stammzellen in Patienten mit ARDS

Author

Jungebluth, P, primary, Holzgraefe, B, additional, Lim, ML, additional, Duru, A, additional, Lundin, V, additional, Sjöqvist, S, additional, Jones, P, additional, Wood, M, additional, Luedde, T, additional, Teixeira, A, additional, Hermanson, O, additional, Winqvist, O, additional, Kalzén, H, additional, Nordin, J, additional, Wiklander, O, additional, EL Andaloussi, S, additional, Alici, E, additional, and Dienemann, H, additional

Published
2015
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39. Minimal information for studies of extracellular vesicles 2018 (MISEV2018):a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

Author

Théry, Clotilde, Witwer, Kenneth W, Aikawa, Elena, Alcaraz, Maria Jose, Anderson, Johnathon D, Andriantsitohaina, Ramaroson, Antoniou, Anna, Arab, Tanina, Archer, Fabienne, Atkin-Smith, Georgia K, Ayre, D Craig, Bach, Jean-Marie, Bachurski, Daniel, Baharvand, Hossein, Balaj, Leonora, Baldacchino, Shawn, Bauer, Natalie N, Baxter, Amy A, Bebawy, Mary, Beckham, Carla, Bedina Zavec, Apolonija, Benmoussa, Abderrahim, Berardi, Anna C, Bergese, Paolo, Bielska, Ewa, Blenkiron, Cherie, Bobis-Wozowicz, Sylwia, Boilard, Eric, Boireau, Wilfrid, Bongiovanni, Antonella, Borràs, Francesc E, Bosch, Steffi, Boulanger, Chantal M, Breakefield, Xandra, Breglio, Andrew M, Brennan, Meadhbh Á, Brigstock, David R, Brisson, Alain, Broekman, Marike Ld, Bromberg, Jacqueline F, Bryl-Górecka, Paulina, Buch, Shilpa, Buck, Amy H, Burger, Dylan, Busatto, Sara, Buschmann, Dominik, Bussolati, Benedetta, Buzás, Edit I, Byrd, James Bryan, Camussi, Giovanni, Carter, David Rf, Caruso, Sarah, Chamley, Lawrence W, Chang, Yu-Ting, Chen, Chihchen, Chen, Shuai, Cheng, Lesley, Chin, Andrew R, Clayton, Aled, Clerici, Stefano P, Cocks, Alex, Cocucci, Emanuele, Coffey, Robert J, Cordeiro-da-Silva, Anabela, Couch, Yvonne, Coumans, Frank Aw, Coyle, Beth, Crescitelli, Rossella, Criado, Miria Ferreira, D'Souza-Schorey, Crislyn, Das, Saumya, Datta Chaudhuri, Amrita, de Candia, Paola, De Santana, Eliezer F, De Wever, Olivier, Del Portillo, Hernando A, Demaret, Tanguy, Deville, Sarah, Devitt, Andrew, Dhondt, Bert, Di Vizio, Dolores, Dieterich, Lothar C, Dolo, Vincenza, Dominguez Rubio, Ana Paula, Dominici, Massimo, Dourado, Mauricio R, Driedonks, Tom Ap, Duarte, Filipe V, Duncan, Heather M, Eichenberger, Ramon M, Ekström, Karin, El Andaloussi, Samir, Elie-Caille, Celine, Erdbrügger, Uta, Falcón-Pérez, Juan M, Fatima, Farah, Fish, Jason E, Flores-Bellver, Miguel, Försönits, András, Frelet-Barrand, Annie, Fricke, Fabia, Fuhrmann, Gregor, Gabrielsson, Susanne, Gámez-Valero, Ana, Gardiner, Chris, Gärtner, Kathrin, Gaudin, Raphael, Gho, Yong Song, Giebel, Bernd, Gilbert, Caroline, Gimona, Mario, Giusti, Ilaria, Goberdhan, Deborah Ci, Görgens, André, Gorski, Sharon M, Greening, David W, Gross, Julia Christina, Gualerzi, Alice, Gupta, Gopal N, Gustafson, Dakota, Handberg, Aase, Haraszti, Reka A, Harrison, Paul, Hegyesi, Hargita, Hendrix, An, Hill, Andrew F, Hochberg, Fred H, Hoffmann, Karl F, Holder, Beth, Holthofer, Harry, Hosseinkhani, Baharak, Hu, Guoku, Huang, Yiyao, Huber, Veronica, Hunt, Stuart, Ibrahim, Ahmed Gamal-Eldin, Ikezu, Tsuneya, Inal, Jameel M, Isin, Mustafa, Ivanova, Alena, Jackson, Hannah K, Jacobsen, Soren, Jay, Steven M, Jayachandran, Muthuvel, Jenster, Guido, Jiang, Lanzhou, Johnson, Suzanne M, Jones, Jennifer C, Jong, Ambrose, Jovanovic-Talisman, Tijana, Jung, Stephanie, Kalluri, Raghu, Kano, Shin-Ichi, Kaur, Sukhbir, Kawamura, Yumi, Keller, Evan T, Khamari, Delaram, Khomyakova, Elena, Khvorova, Anastasia, Kierulf, Peter, Kim, Kwang Pyo, Kislinger, Thomas, Klingeborn, Mikael, Klinke, David J, Kornek, Miroslaw, Kosanović, Maja M, Kovács, Árpád Ferenc, Krämer-Albers, Eva-Maria, Krasemann, Susanne, Krause, Mirja, Kurochkin, Igor V, Kusuma, Gina D, Kuypers, Sören, Laitinen, Saara, Langevin, Scott M, Languino, Lucia R, Lannigan, Joanne, Lässer, Cecilia, Laurent, Louise C, Lavieu, Gregory, Lázaro-Ibáñez, Elisa, Le Lay, Soazig, Lee, Myung-Shin, Lee, Yi Xin Fiona, Lemos, Debora S, Lenassi, Metka, Leszczynska, Aleksandra, Li, Isaac Ts, Liao, Ke, Libregts, Sten F, Ligeti, Erzsebet, Lim, Rebecca, Lim, Sai Kiang, Linē, Aija, Linnemannstöns, Karen, Llorente, Alicia, Lombard, Catherine A, Lorenowicz, Magdalena J, Lörincz, Ákos M, Lötvall, Jan, Lovett, Jason, Lowry, Michelle C, Loyer, Xavier, Lu, Quan, Lukomska, Barbara, Lunavat, Taral R, Maas, Sybren Ln, Malhi, Harmeet, Marcilla, Antonio, Mariani, Jacopo, Mariscal, Javier, Martens-Uzunova, Elena S, Martin-Jaular, Lorena, Martinez, M Carmen, Martins, Vilma Regina, Mathieu, Mathilde, Mathivanan, Suresh, Maugeri, Marco, McGinnis, Lynda K, McVey, Mark J, Meckes, David G, Meehan, Katie L, Mertens, Inge, Minciacchi, Valentina R, Möller, Andreas, Møller Jørgensen, Malene, Morales-Kastresana, Aizea, Morhayim, Jess, Mullier, François, Muraca, Maurizio, Musante, Luca, Mussack, Veronika, Muth, Dillon C, Myburgh, Kathryn H, Najrana, Tanbir, Nawaz, Muhammad, Nazarenko, Irina, Nejsum, Peter, Neri, Christian, Neri, Tommaso, Nieuwland, Rienk, Nimrichter, Leonardo, Nolan, John P, Nolte-'t Hoen, Esther NM, Noren Hooten, Nicole, O'Driscoll, Lorraine, O'Grady, Tina, O'Loghlen, Ana, Ochiya, Takahiro, Olivier, Martin, Ortiz, Alberto, Ortiz, Luis A, Osteikoetxea, Xabier, Østergaard, Ole, Ostrowski, Matias, Park, Jaesung, Pegtel, D Michiel, Peinado, Hector, Perut, Francesca, Pfaffl, Michael W, Phinney, Donald G, Pieters, Bartijn Ch, Pink, Ryan C, Pisetsky, David S, Pogge von Strandmann, Elke, Polakovicova, Iva, Poon, Ivan Kh, Powell, Bonita H, Prada, Ilaria, Pulliam, Lynn, Quesenberry, Peter, Radeghieri, Annalisa, Raffai, Robert L, Raimondo, Stefania, Rak, Janusz, Ramirez, Marcel I, Raposo, Graça, Rayyan, Morsi S, Regev-Rudzki, Neta, Ricklefs, Franz L, Robbins, Paul D, Roberts, David D, Rodrigues, Silvia C, Rohde, Eva, Rome, Sophie, Rouschop, Kasper Ma, Rughetti, Aurelia, Russell, Ashley E, Saá, Paula, Sahoo, Susmita, Salas-Huenuleo, Edison, Sánchez, Catherine, Saugstad, Julie A, Saul, Meike J, Schiffelers, Raymond M, Schneider, Raphael, Schøyen, Tine Hiorth, Scott, Aaron, Shahaj, Eriomina, Sharma, Shivani, Shatnyeva, Olga, Shekari, Faezeh, Shelke, Ganesh Vilas, Shetty, Ashok K, Shiba, Kiyotaka, Siljander, Pia R-M, Silva, Andreia M, Skowronek, Agata, Snyder, Orman L, Soares, Rodrigo Pedro, Sódar, Barbara W, Soekmadji, Carolina, Sotillo, Javier, Stahl, Philip D, Stoorvogel, Willem, Stott, Shannon L, Strasser, Erwin F, Swift, Simon, Tahara, Hidetoshi, Tewari, Muneesh, Timms, Kate, Tiwari, Swasti, Tixeira, Rochelle, Tkach, Mercedes, Toh, Wei Seong, Tomasini, Richard, Torrecilhas, Ana Claudia, Tosar, Juan Pablo, Toxavidis, Vasilis, Urbanelli, Lorena, Vader, Pieter, van Balkom, Bas Wm, van der Grein, Susanne G, Van Deun, Jan, van Herwijnen, Martijn Jc, Van Keuren-Jensen, Kendall, van Niel, Guillaume, van Royen, Martin E, van Wijnen, Andre J, Vasconcelos, M Helena, Vechetti, Ivan J, Veit, Tiago D, Vella, Laura J, Velot, Émilie, Verweij, Frederik J, Vestad, Beate, Viñas, Jose L, Visnovitz, Tamás, Vukman, Krisztina V, Wahlgren, Jessica, Watson, Dionysios C, Wauben, Marca Hm, Weaver, Alissa, Webber, Jason P, Weber, Viktoria, Wehman, Ann M, Weiss, Daniel J, Welsh, Joshua A, Wendt, Sebastian, Wheelock, Asa M, Wiener, Zoltán, Witte, Leonie, Wolfram, Joy, Xagorari, Angeliki, Xander, Patricia, Xu, Jing, Yan, Xiaomei, Yáñez-Mó, María, Yin, Hang, Yuana, Yuana, Zappulli, Valentina, Zarubova, Jana, Žėkas, Vytautas, Zhang, Jian-Ye, Zhao, Zezhou, Zheng, Lei, Zheutlin, Alexander R, Zickler, Antje M, Zimmermann, Pascale, Zivkovic, Angela M, Zocco, Davide, Zuba-Surma, Ewa K, dB&C I&I, LS Celbiologie-Algemeen, Celbiologie, Afd Pharmaceutics, Sub General Pharmaceutics, Sub Biomol.Mass Spect. and Proteomics, Afd Pharmacology, Urology, Pathology, Medical Oncology, Immunité et cancer, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Johns Hopkins University School of Medicine [Baltimore], Stress Oxydant et Pathologies Métaboliques (SOPAM), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192 (PRISM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Infections Virales et Pathologie Comparée - UMR 754 (IVPC), Institut National de la Recherche Agronomique (INRA)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Immuno-Endocrinologie Cellulaire et Moléculaire [Nantes] (IECM), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Department for Molecular Biology and Nanobiotechnology, National Institute of chemitry, Slovenia, Biologie, génétique et thérapies ostéoarticulaires et respiratoires (BIOTARGEN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Immuno-Endocrinologie Cellulaire et Moléculaire (IECM), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes, Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Imagerie Moléculaire et Nanobiotechnologies - Institut Européen de Chimie et Biologie (IECB), Université Sciences et Technologies - Bordeaux 1-Centre National de la Recherche Scientifique (CNRS), Molecular Biotechnology Center, Università degli studi di Torino = University of Turin (UNITO), Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Centre for Sustainable Tropical Fisheries and Aquaculture, James Cook University (JCU), Department of Oncology - Pathology, Cancer Center Karolinska [Karolinska Institutet] (CCK), Karolinska Institutet [Stockholm]-Karolinska Institutet [Stockholm], Departamento de Ciências Biológicas, Universidade do Porto = University of Porto, Laboratory of Experimental Cancer Research, Department of Radiation Oncology and Experimental Cancer Research, Cancer Research Institute Ghent (CRIG), Universiteit Gent = Ghent University [Belgium] (UGENT), Department of Medical and Surgical Sciences for Children and Adults [Modena, Italy] (Laboratory of Cellular Therapy), Università degli Studi di Modena e Reggio Emilia (UNIMORE), Clinical Research Center, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Huddinge, Sweden, Karolinska Institutet [Stockholm]-Karolinska University Hospital [Stockholm], Center for Cooperative Research in Biosciences (CIC bioGUNE), Partner site Munich, German Centre for Infection Research (DZIF), Institute for Transfusion Medicine, University Hospital Essen, Universität Duisburg-Essen [Essen], Mécanismes Adaptatifs et Evolution (MECADEV), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Psychiatry, Institute of Biological, Environmental and Rural Sciences (IBERS), Aberystwyth University, Department of Bacteriology and Immunology [Helsinki], Haartman Institute [Helsinki], Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Rigshospitalet [Copenhagen], Copenhagen University Hospital, Dalhousie University [Halifax], Department of Biology, Molecular Cell Biology, University of Mainz, Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU), Glycobiologie et signalisation cellulaire, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, University of Gothenburg (GU), Universidad de Alicante, École supérieure du professorat et de l'éducation - Académie de Créteil (UPEC ESPE Créteil), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), University of Antwerp (UA), Université Catholique de Louvain = Catholic University of Louvain (UCL), Research Institute, IRCCS Ospedale Pediatrico Bambino Gesù [Roma], Department of Veterinary Disease Biology [Copenhagen], Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), Biologie et Pathologie du Neurone (Brain-C), Adaptation Biologique et Vieillissement = Biological Adaptation and Ageing (B2A), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Mathematics and Statistics, American University, University of Pretoria [South Africa], Ecole des Ingénieurs de la Ville de Paris (EIVP), Universitat Pompeu Fabra [Barcelona] (UPF), Instituto de Investigaciones Biomedicas, Universidad Nacional Autónoma de México (UNAM), Istituto Ortopedico Rizzoli, Department of Molecular Therapeutics, The Scripps Research Institute, Laboratoire d'Informatique de Grenoble (LIG ), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Montreal Children's Hospital, McGill University Health Center [Montreal] (MUHC), Compartimentation et dynamique cellulaires (CDC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Curie [Paris]-Centre National de la Recherche Scientifique (CNRS), National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cardiovascular Research Center, Massachusetts General Hospital [Boston], University Medical Center [Utrecht], University of Toronto, Fiocruz Minas - René Rachou Research Center / Instituto René Rachou [Belo Horizonte, Brésil], Fundação Oswaldo Cruz (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Federal University of Sao Paulo (Unifesp), Functional Genomics / Genómica Funcional [Montevideo], Institut Pasteur de Montevideo, Dipartimento di Medicina Sperimentale e Scienze Biochimiche, Università degli Studi di Perugia (UNIPG), Hospital Santa Cristina Instituto de Investigación Sanitaria Princesa C, Unidad de Investigación, Institut Curie [Paris]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Department of Physiology, University of California [San Francisco] (UCSF), University of California-University of California, University of Vermont [Burlington], Peking University [Beijing], Shandong Agricultural University (SDAU), State Key Laboratory of Quality Research in Chinese Medicine Taipa, Macau SAR, (Institute of Chinese Medical Sciences), Human Genetics, Universität Ulm - Ulm University [Ulm, Allemagne], INSERM, Institut Curie, INCa [INCA-11548], French National Research Agency [ANR-10-IDEX-0001-02 PSL*, ANR-11-LABX-0043], SIDACTION [17-1-AAE-1138], Fondation ARC [PGA1 RF20180206962, PJA 20171206453], NIDA [DA040385, DA047807], Ministry of Education, NIA [AG057430], NIMH [MH118164], Institut National de la Recherche Agronomique (INRA)-École Pratique des Hautes Études (EPHE), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN), Université Sciences et Technologies - Bordeaux 1 (UB)-Centre National de la Recherche Scientifique (CNRS), Universiteit Gent = Ghent University (UGENT), Università degli Studi di Modena e Reggio Emilia = University of Modena and Reggio Emilia (UNIMORE), Universität Duisburg-Essen = University of Duisburg-Essen [Essen], Biotechnology and Biological Sciences Research Council (BBSRC)-Aberystwyth University, University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), Universidad Nacional Autónoma de México = National Autonomous University of Mexico (UNAM), The Scripps Research Institute [La Jolla, San Diego], Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), Università degli Studi di Perugia = University of Perugia (UNIPG), Instituto de Investigacion Sanitaria del Hospital de la Princesa, Hospital Universitario de La Princesa, University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC), ANR-17-CE09-0025,MADNESS,Une approche microfluidique générique pour la qualification des nanoparticules biologiques(2017), Institut National de la Recherche Agronomique (INRA)-École pratique des hautes études (EPHE)-Université Claude Bernard Lyon 1 (UCBL), Biomedical Engineering and Physics, ACS - Atherosclerosis & ischemic syndromes, ACS - Microcirculation, Laboratory Specialized Diagnostics & Research, Radiotherapie, RS: GROW - R2 - Basic and Translational Cancer Biology, Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Université Nice Sophia Antipolis (... - 2019) (UNS), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), Ecole Nationale Vétérinaire de Nantes-Université de Nantes (UN)-Institut National de la Recherche Agronomique (INRA), Università degli studi di Torino (UNITO), Universidade do Porto, University of Helsinki-University of Helsinki-Faculty of Medecine [Helsinki], University of Helsinki-University of Helsinki, Johannes Gutenberg - Universität Mainz (JGU), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Université Pierre et Marie Curie - Paris 6 (UPMC), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Université de Toronto [Canada], Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192 (PRISM), Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Université de Franche-Comté (UFC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Technologie de Belfort-Montbeliard (UTBM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM), Universidade do Porto [Porto], Ghent University [Belgium] (UGENT), FEMTO-ST Institute, Université de Technologie de Belfort-Montbeliard (UTBM)-Université de Franche-Comté (UFC)-CNRS : UMR6174, Mécanismes adaptatifs : des organismes aux communautés (MECADEV), Centre National de la Recherche Scientifique (CNRS)-Muséum national d'Histoire naturelle (MNHN), Johannes Gutenberg - University of Mainz (JGU), Université Catholique de Louvain (UCL), Universitat Pompeu Fabra [Barcelona], Laboratoire d'Informatique de Grenoble (LIG), Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Centre National de la Recherche Scientifique (CNRS)-Institut Curie-Université Pierre et Marie Curie - Paris 6 (UPMC), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Laboratoire Réactions et Génie des Procédés (LRGP), Fiocruz Minas - René Rachou Research Center / Instituto René Rachou, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Functional Genomics Unit, Institut Curie-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), University of Vermont College of Medicine [Burlington, VT, USA], Extracellular Vesicles, Molecular and Integrative Biosciences Research Programme, Thery, C., Witwer, K. W., Aikawa, E., Alcaraz, M. J., Anderson, J. D., Andriantsitohaina, R., Antoniou, A., Arab, T., Archer, F., Atkin-Smith, G. K., Ayre, D. C., Bach, J. -M., Bachurski, D., Baharvand, H., Balaj, L., Baldacchino, S., Bauer, N. N., Baxter, A. A., Bebawy, M., Beckham, C., Bedina Zavec, A., Benmoussa, A., Berardi, A. C., Bergese, P., Bielska, E., Blenkiron, C., Bobis-Wozowicz, S., Boilard, E., Boireau, W., Bongiovanni, A., Borras, F. E., Bosch, S., Boulanger, C. M., Breakefield, X., Breglio, A. M., Brennan, M. A., Brigstock, D. R., Brisson, A., Broekman, M. L. D., Bromberg, J. F., Bryl-Gorecka, P., Buch, S., Buck, A. H., Burger, D., Busatto, S., Buschmann, D., Bussolati, B., Buzas, E. I., Byrd, J. B., Camussi, G., Carter, D. R. F., Caruso, S., Chamley, L. W., Chang, Y. -T., Chaudhuri, A. D., Chen, C., Chen, S., Cheng, L., Chin, A. R., Clayton, A., Clerici, S. P., Cocks, A., Cocucci, E., Coffey, R. J., Cordeiro-da-Silva, A., Couch, Y., Coumans, F. A. W., Coyle, B., Crescitelli, R., Criado, M. F., D'Souza-Schorey, C., Das, S., de Candia, P., De Santana, E. F., De Wever, O., del Portillo, H. A., Demaret, T., Deville, S., Devitt, A., Dhondt, B., Di Vizio, D., Dieterich, L. C., Dolo, V., Dominguez Rubio, A. P., Dominici, M., Dourado, M. R., Driedonks, T. A. P., Duarte, F. V., Duncan, H. M., Eichenberger, R. M., Ekstrom, K., EL Andaloussi, S., Elie-Caille, C., Erdbrugger, U., Falcon-Perez, J. M., Fatima, F., Fish, J. E., Flores-Bellver, M., Forsonits, A., Frelet-Barrand, A., Fricke, F., Fuhrmann, G., Gabrielsson, S., Gamez-Valero, A., Gardiner, C., Gartner, K., Gaudin, R., Gho, Y. S., Giebel, B., Gilbert, C., Gimona, M., Giusti, I., Goberdhan, D. C. I., Gorgens, A., Gorski, S. M., Greening, D. W., Gross, J. C., Gualerzi, A., Gupta, G. N., Gustafson, D., Handberg, A., Haraszti, R. A., Harrison, P., Hegyesi, H., Hendrix, A., Hill, A. F., Hochberg, F. H., Hoffmann, K. F., Holder, B., Holthofer, H., Hosseinkhani, B., Hu, G., Huang, Y., Huber, V., Hunt, S., Ibrahim, A. G. -E., Ikezu, T., Inal, J. M., Isin, M., Ivanova, A., Jackson, H. K., Jacobsen, S., Jay, S. M., Jayachandran, M., Jenster, G., Jiang, L., Johnson, S. M., Jones, J. C., Jong, A., Jovanovic-Talisman, T., Jung, S., Kalluri, R., Kano, S. -I., Kaur, S., Kawamura, Y., Keller, E. T., Khamari, D., Khomyakova, E., Khvorova, A., Kierulf, P., Kim, K. P., Kislinger, T., Klingeborn, M., Klinke, D. J., Kornek, M., Kosanovic, M. M., Kovacs, A. F., Kramer-Albers, E. -M., Krasemann, S., Krause, M., Kurochkin, I. V., Kusuma, G. D., Kuypers, S., Laitinen, S., Langevin, S. M., Languino, L. R., Lannigan, J., Lasser, C., Laurent, L. C., Lavieu, G., Lazaro-Ibanez, E., Le Lay, S., Lee, M. -S., Lee, Y. X. F., Lemos, D. S., Lenassi, M., Leszczynska, A., Li, I. T. S., Liao, K., Libregts, S. F., Ligeti, E., Lim, R., Lim, S. K., Line, A., Linnemannstons, K., Llorente, A., Lombard, C. A., Lorenowicz, M. J., Lorincz, A. M., Lotvall, J., Lovett, J., Lowry, M. C., Loyer, X., Lu, Q., Lukomska, B., Lunavat, T. R., Maas, S. L. N., Malhi, H., Marcilla, A., Mariani, J., Mariscal, J., Martens-Uzunova, E. S., Martin-Jaular, L., Martinez, M. C., Martins, V. R., Mathieu, M., Mathivanan, S., Maugeri, M., Mcginnis, L. K., Mcvey, M. J., Meckes, D. G., Meehan, K. L., Mertens, I., Minciacchi, V. R., Moller, A., Moller Jorgensen, M., Morales-Kastresana, A., Morhayim, J., Mullier, F., Muraca, M., Musante, L., Mussack, V., Muth, D. C., Myburgh, K. H., Najrana, T., Nawaz, M., Nazarenko, I., Nejsum, P., Neri, C., Neri, T., Nieuwland, R., Nimrichter, L., Nolan, J. P., Nolte-'t Hoen, E. N. M., Noren Hooten, N., O'Driscoll, L., O'Grady, T., O'Loghlen, A., Ochiya, T., Olivier, M., Ortiz, A., Ortiz, L. A., Osteikoetxea, X., Ostegaard, O., Ostrowski, M., Park, J., Pegtel, D. M., Peinado, H., Perut, F., Pfaffl, M. W., Phinney, D. G., Pieters, B. C. H., Pink, R. C., Pisetsky, D. S., Pogge von Strandmann, E., Polakovicova, I., Poon, I. K. H., Powell, B. H., Prada, I., Pulliam, L., Quesenberry, P., Radeghieri, A., Raffai, R. L., Raimondo, S., Rak, J., Ramirez, M. I., Raposo, G., Rayyan, M. S., Regev-Rudzki, N., Ricklefs, F. L., Robbins, P. D., Roberts, D. D., Rodrigues, S. C., Rohde, E., Rome, S., Rouschop, K. M. A., Rughetti, A., Russell, A. E., Saa, P., Sahoo, S., Salas-Huenuleo, E., Sanchez, C., Saugstad, J. A., Saul, M. J., Schiffelers, R. M., Schneider, R., Schoyen, T. H., Scott, A., Shahaj, E., Sharma, S., Shatnyeva, O., Shekari, F., Shelke, G. V., Shetty, A. K., Shiba, K., Siljander, P. R. -M., Silva, A. M., Skowronek, A., Snyder, O. L., Soares, R. P., Sodar, B. W., Soekmadji, C., Sotillo, J., Stahl, P. D., Stoorvogel, W., Stott, S. L., Strasser, E. F., Swift, S., Tahara, H., Tewari, M., Timms, K., Tiwari, S., Tixeira, R., Tkach, M., Toh, W. S., Tomasini, R., Torrecilhas, A. C., Tosar, J. P., Toxavidis, V., Urbanelli, L., Vader, P., van Balkom, B. W. M., van der Grein, S. G., Van Deun, J., van Herwijnen, M. J. C., Van Keuren-Jensen, K., van Niel, G., van Royen, M. E., van Wijnen, A. J., Vasconcelos, M. H., Vechetti, I. J., Veit, T. D., Vella, L. J., Velot, E., Verweij, F. J., Vestad, B., Vinas, J. L., Visnovitz, T., Vukman, K. V., Wahlgren, J., Watson, D. C., Wauben, M. H. M., Weaver, A., Webber, J. P., Weber, V., Wehman, A. M., Weiss, D. J., Welsh, J. A., Wendt, S., Wheelock, A. M., Wiener, Z., Witte, L., Wolfram, J., Xagorari, A., Xander, P., Xu, J., Yan, X., Yanez-Mo, M., Yin, H., Yuana, Y., Zappulli, V., Zarubova, J., Zekas, V., Zhang, J. -Y., Zhao, Z., Zheng, L., Zheutlin, A. R., Zickler, A. M., Zimmermann, P., Zivkovic, A. M., Zocco, D., Zuba-Surma, E. K., dB&C I&I, LS Celbiologie-Algemeen, Celbiologie, Afd Pharmaceutics, Sub General Pharmaceutics, Sub Biomol.Mass Spect. and Proteomics, Afd Pharmacology, CCA - Imaging and biomarkers, Amsterdam Neuroscience - Neuroinfection & -inflammation, and Amsterdam Neuroscience - Cellular & Molecular Mechanisms

Subjects
ectosome, ectosomes, exosomes, extracellular vesicles, guidelines, microparticles, microvesicles, minimal information requirements, reproducibility, rigor, standardization, Histology, Cell Biology, [SDV]Life Sciences [q-bio], size-exclusion, Medicine and Health Sciences, CELL-DERIVED MICROPARTICLES, FIELD-FLOW FRACTIONATION, requirements, circulating, ComputingMilieux_MISCELLANEOUS, Manchester Cancer Research Centre, lcsh:Cytology, PROSTATE-CANCER, microparticle, Cell interaction, microvesicle, chromatography, Position Paper, guideline, Life Sciences & Biomedicine, ectosomes, exosomes, extracellular vesicles, guidelines, microparticles, microvesicles, minimal information requirements, reproducibility, rigor, standardization, MEMBRANE-VESICLES, FETAL BOVINE, Ectosomes, Exosomes, Extracellular Vesicles, Guidelines, Microparticles, Microvesicles, Minimal Information Requirements, Reproducibility, Rigor, Standardization, CIRCULATING MICROPARTICLES, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, ddc:570, exosome, SURFACE-PLASMON RESONANCE, ddc:610, lcsh:QH573-671, Biology, Interacció cel·lular, Science & Technology, ResearchInstitutes_Networks_Beacons/mcrc, Cell membranes, HUMAN URINARY EXOSOMES, PREANALYTICAL PARAMETERS, minimal information requirement, SIZE-EXCLUSION CHROMATOGRAPHY, 1182 Biochemistry, cell and molecular biology, extracellular vesicle, Human medicine, Membranes cel·lulars
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.

Published
2018

40. Evidence-Based Clinical Use of Nanoscale Extracellular Vesicles in Nanomedicine

Author

Guillaume van Niel, Carla Oliveira, Roberto Furlan, Ihsan Gursel, Anabela Cordeiro da Silva, Edit I. Buzás, Samir El Andaloussi, Eva Rohde, Alicia Llorente, Hernando A. del Portillo, Graça Raposo, Bernd Giebel, An Hendrix, Maja Kosanović, Lorraine O'Driscoll, Natasa Zarovni, Apolonija Bedina Zavec, Stefano Fais, Bertrand Kaeffer, Giovanni Camussi, Gabriella Pocsfalvi, María Yáñez-Mó, Irina Nazarenko, Tanja Ficko Trček, Marei Sammar, Lawrence Rajendran, Marjo Yliperttula, Antonio Marcilla, Francesc E. Borràs, Marilena E. Lekka, Joana Carvalho, Georg Lipps, Pia Siljander, Veronika Kralj-Iglič, Francesco Cappello, M. Helena Vasconcelos, Mariantonia Logozzi, Istituto Superiore di Sanità, Trinity College Dublin, Hospital Germans Trias I Pujol, Department of Genetics, Cell- and Immunobiology, Semmelweis University, Universita di Torino, Università degli Studi di Palermo, Institute of Molecular Pathology and Immunology, Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Institute for Molecular and Cell Biology, University of Porto Medical School, Hospital Clínic de Barcelona, Karolinska Institutet [Stockholm], University of Oxford [Oxford], Lek Pharmaceuticals d.d., a Sandoz Company, San Raffaele Scientific Institute, Ghent University Hospital, Bilkent University [Ankara], University of Ljubljana, Physiologie des Adaptations Nutritionnelles (PhAN), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN), University of Belgrade, University of Ioannina, University of Applied Sciences and Arts Northwestern Switzerland (HES-SO), Universitat de València (UV), ORT Braude College, Partenaires INRAE, Oslo University Hospital [Oslo], University of Freiburg [Freiburg], Universidade do Porto, Consiglio Nazionale delle Ricerche (CNR), Universität Zürich [Zürich] = University of Zurich (UZH), Biologie Cellulaire et Cancer, Institut Curie [Paris]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut Curie [Paris], Paracelsus Medical University, University of Salzburg, University of Helsinki, Univ Porto IPATIMUP, Inst Mol Pathol & Immunol, P-4200135 Oporto, Portugal, Univ Porto IPATIMUP, Inst Invest & Inovacao Saude i3S, P-4200135 Oporto, Portugal, Hospital Sta Cristina, Exosomics Siena SpA, National Institute of Chemistry, Institute for Transfusion Medicine, University Hospital Essen, Universität Duisburg-Essen [Essen], Fais, S., O'Driscoll, L., Borras, F., Buzas, E., Camussi, G., Cappello, F., Carvalho, J., Cordeiro Da Silva, A., Del Portillo, H., El Andaloussi, S., Ficko Trček, T., Furlan, R., Hendrix, A., Gursel, I., Kralj-Iglic, V., Kaeffer, B., Kosanovic, M., Lekka, M., Lipps, G., Logozzi, M., Marcilla, A., Sammar, M., Llorente, A., Nazarenko, I., Oliveira, C., Pocsfalvi, G., Rajendran, L., Raposo, G., Rohde, E., Siljander, P., Van Niel, G., Vasconcelos, M., Yáñez-Mó, M., Yliperttula, M., Zarovni, N., Zavec, A., and Giebel, B.

Subjects
0301 basic medicine, Medical nanotechnology, Physiology, Medizin, General Physics and Astronomy, xxx xxx, Cell Communication, Exosomes, Regenerative medicine, Theranostic Nanomedicine, Membrane microparticle, Engineering (all), Drug Delivery Systems, Pathophysiological, Cell-Derived Microparticles, Caveolae, Diagnosis, General Materials Science, Lipid raft, Phospholipids, Clinical Trials as Topic, Phospholipid membrane, Vesicle, General Engineering, Science and Technology, Materials Science (all), Physics and Astronomy (all), 3. Good health, Cell biology, Intercellular communications, Clinical trial (topic), Nanomedicine, Drug delivery, [SDV.IMM]Life Sciences [q-bio]/Immunology, Human, Endosome, Drug delivery system, Nanotechnology, Biology, Program diagnostics, 03 medical and health sciences, Extracellular Vesicles, Animals, Humans, Therapeutic agents, Settore BIO/16 - Anatomia Umana, Animal, Recent researches, Microvesicles, Cell membranes, Exosome, 030104 developmental biology, International cooperation, Membrane microdomains
Abstract

collaboration au projet H2020 European Cooperation in Science and Technology (COST) program European Network on Microvesicles and Exosomes in Health and Disease (ME-HAD); International audience; 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.

Published
2016

41. Novel Endogenous Engineering Platform for Robust Loading and Delivery of Functional mRNA by Extracellular Vesicles.

Author

Zickler AM, Liang X, Gupta D, Mamand DR, De Luca M, Corso G, Errichelli L, Hean J, Sen T, Elsharkasy OM, Kamei N, Niu Z, Zhou G, Zhou H, Roudi S, Wiklander OPB, Görgens A, Nordin JZ, Castilla-Llorente V, and El Andaloussi S

Abstract

Messenger RNA (mRNA) has emerged as an attractive therapeutic molecule for a plethora of clinical applications. For in vivo functionality, mRNA therapeutics require encapsulation into effective, stable, and safe delivery systems to protect the cargo from degradation and reduce immunogenicity. Here, a bioengineering platform for efficient mRNA loading and functional delivery using bionormal nanoparticles, extracellular vesicles (EVs), is established by expressing a highly specific RNA-binding domain fused to CD63 in EV producer cells stably expressing the target mRNA. The additional combination with a fusogenic endosomal escape moiety, Vesicular Stomatitis Virus Glycoprotein, enables functional mRNA delivery in vivo at doses substantially lower than currently used clinically with synthetic lipid-based nanoparticles. Importantly, the application of EVs loaded with effective cancer immunotherapy proves highly effective in an aggressive melanoma mouse model. This technology addresses substantial drawbacks currently associated with EV-based nucleic acid delivery systems and is a leap forward to clinical EV applications., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Published
2024
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42. Extracellular vesicles originating from melanoma cells promote dysregulation in haematopoiesis as a component of cancer immunoediting.

Author

Mamand DR, Bazaz S, Mohammad DK, Liang X, Pavlova S, Mim C, Gabrielsson S, Nordin JZ, Wiklander OPB, Abedi-Valugerdi M, and El-Andaloussi S

Subjects
Animals, Mice, Melanoma, Experimental metabolism, Melanoma, Experimental immunology, Melanoma, Experimental pathology, Mice, Inbred C57BL, Vascular Endothelial Growth Factor A metabolism, Cell Line, Tumor, Extracellular Vesicles metabolism, Extracellular Vesicles immunology, Hematopoiesis
Abstract

Haematopoiesis dysregulation with the presence of immature myeloid and erythroid immunosuppressive cells are key characteristics of the immune escape phase of tumour development. Here, the role of in vitro generated B16F10 tumour cell-derived extracellular vesicles (tEVs) as indirect cellular communicators, participating in tumour-induced dysregulation of haematopoiesis, was explored. The isolated tEVs displayed features of small EVs with a size range of 100-200 nm, expressed the common EV markers CD63, CD9, and Alix, and had a spherical shape with a lipid bilayer membrane. Proteomic profiling revealed significant levels of angiogenic factors, particularly vascular endothelial growth factor (VEGF), osteopontin, and tissue factor, associated with the tEVs. Systemic administration of these tEVs in syngeneic mice induced splenomegaly and disrupted haematopoiesis, leading to extramedullary haematopoiesis, expansion of splenic immature erythroid progenitors, reduced bone marrow cellularity, medullary expansion of granulocytic myeloid suppressor cells, and the development of anaemia. These effects closely mirrored those observed in tumour-bearing mice and were not seen after heat inactivating the tEVs. In vitro studies demonstrated that tEVs independently induced the expansion of bone marrow granulocytic myeloid suppressor cells and B cells while reducing the frequency of cells in the erythropoietic lineage. These effects of tEVs were significantly abrogated by the blockade of VEGF or heat inactivation. Our findings underscore the important role of tEVs in dysregulating haematopoiesis during the immune escape phase of cancer immunoediting, suggesting their potential as targets for addressing immune evasion and reinstating normal hematopoietic processes., (© 2024 The Author(s). Journal of Extracellular Vesicles published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.)

Published
2024
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43. Inter-laboratory multiplex bead-based surface protein profiling of MSC-derived EV preparations identifies MSC-EV surface marker signatures.

Author

Nguyen VVT, Welsh JA, Tertel T, Choo A, van de Wakker SI, Defourny KAY, Giebel B, Vader P, Padmanabhan J, Lim SK, Nolte-'t Hoen ENM, Verhaar MC, Bostancioglu RB, Zickler AM, Hong JM, Jones JC, El Andaloussi S, van Balkom BWM, and Görgens A

Subjects
Humans, Flow Cytometry methods, Membrane Proteins metabolism, Membrane Proteins analysis, Cells, Cultured, Antigens, CD metabolism, Mesenchymal Stem Cells metabolism, Mesenchymal Stem Cells cytology, Extracellular Vesicles metabolism, Extracellular Vesicles chemistry, Biomarkers metabolism
Abstract

Mesenchymal stromal cells (MSCs) are promising regenerative therapeutics that primarily exert their effects through secreted extracellular vesicles (EVs). These EVs - being small and non-living - are easier to handle and possess advantages over cellular products. Consequently, the therapeutic potential of MSC-EVs is increasingly investigated. However, due to variations in MSC-EV manufacturing strategies, MSC-EV products should be considered as highly diverse. Moreover, the diverse array of EV characterisation technologies used for MSC-EV characterisation further complicates reliable interlaboratory comparisons of published data. Consequently, this study aimed to establish a common method that can easily be used by various MSC-EV researchers to characterise MSC-EV preparations to facilitate interlaboratory comparisons. To this end, we conducted a comprehensive inter-laboratory assessment using a novel multiplex bead-based EV flow cytometry assay panel. This assessment involved 11 different MSC-EV products from five laboratories with varying MSC sources, culture conditions, and EV preparation methods. Through this assay panel covering a range of mostly MSC-related markers, we identified a set of cell surface markers consistently positive (CD44, CD73 and CD105) or negative (CD11b, CD45 and CD197) on EVs of all explored MSC-EV preparations. Hierarchical clustering analysis revealed distinct surface marker profiles associated with specific preparation processes and laboratory conditions. We propose CD73, CD105 and CD44 as robust positive markers for minimally identifying MSC-derived EVs and CD11b, CD14, CD19, CD45 and CD79 as reliable negative markers. Additionally, we highlight the influence of culture medium components, particularly human platelet lysate, on EV surface marker profiles, underscoring the influence of culture conditions on resulting EV products. This standardisable approach for MSC-EV surface marker profiling offers a tool for routine characterisation of manufactured EV products in pre-clinical and clinical research, enhances the quality control of MSC-EV preparations, and hopefully paves the way for higher consistency and reproducibility in the emerging therapeutic MSC-EV field., (© 2024 The Author(s). Journal of Extracellular Vesicles published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.)

Published
2024
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44. Antibody-displaying extracellular vesicles for targeted cancer therapy.

Author

Wiklander OPB, Mamand DR, Mohammad DK, Zheng W, Jawad Wiklander R, Sych T, Zickler AM, Liang X, Sharma H, Lavado A, Bost J, Roudi S, Corso G, Lennaárd AJ, Abedi-Valugerdi M, Mäger I, Alici E, Sezgin E, Nordin JZ, Gupta D, Görgens A, and El Andaloussi S

Abstract

Extracellular vesicles (EVs) function as natural delivery vectors and mediators of biological signals across tissues. Here, by leveraging these functionalities, we show that EVs decorated with an antibody-binding moiety specific for the fragment crystallizable (Fc) domain can be used as a modular delivery system for targeted cancer therapy. The Fc-EVs can be decorated with different types of immunoglobulin G antibody and thus be targeted to virtually any tissue of interest. Following optimization of the engineered EVs by screening Fc-binding and EV-sorting moieties, we show the targeting of EVs to cancer cells displaying the human epidermal receptor 2 or the programmed-death ligand 1, as well as lower tumour burden and extended survival of mice with subcutaneous melanoma tumours when systemically injected with EVs displaying an antibody for the programmed-death ligand 1 and loaded with the chemotherapeutic doxorubicin. EVs with Fc-binding domains may be adapted to display other Fc-fused proteins, bispecific antibodies and antibody-drug conjugates., (© 2024. The Author(s).)

Published
2024
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45. Phosphatidylserine-exposing extracellular vesicles in body fluids are an innate defence against apoptotic mimicry viral pathogens.

Author

Groß R, Reßin H, von Maltitz P, Albers D, Schneider L, Bley H, Hoffmann M, Cortese M, Gupta D, Deniz M, Choi JY, Jansen J, Preußer C, Seehafer K, Pöhlmann S, Voelker DR, Goffinet C, Pogge-von Strandmann E, Bunz U, Bartenschlager R, El Andaloussi S, Sparrer KMJ, Herker E, Becker S, Kirchhoff F, Münch J, and Müller JA

Subjects
Female, Humans, Phosphatidylserines, Virus Attachment, Viruses, Extracellular Vesicles, Zika Virus, Body Fluids, Zika Virus Infection
Abstract

Some viruses are rarely transmitted orally or sexually despite their presence in saliva, breast milk, or semen. We previously identified that extracellular vesicles (EVs) in semen and saliva inhibit Zika virus infection. However, the antiviral spectrum and underlying mechanism remained unclear. Here we applied lipidomics and flow cytometry to show that these EVs expose phosphatidylserine (PS). By blocking PS receptors, targeted by Zika virus in the process of apoptotic mimicry, they interfere with viral attachment and entry. Consequently, physiological concentrations of EVs applied in vitro efficiently inhibited infection by apoptotic mimicry dengue, West Nile, Chikungunya, Ebola and vesicular stomatitis viruses, but not severe acute respiratory syndrome coronavirus 2, human immunodeficiency virus 1, hepatitis C virus and herpesviruses that use other entry receptors. Our results identify the role of PS-rich EVs in body fluids in innate defence against infection via viral apoptotic mimicries, explaining why these viruses are primarily transmitted via PS-EV-deficient blood or blood-ingesting arthropods rather than direct human-to-human contact., (© 2024. The Author(s).)

Published
2024
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46. High-throughput measurement of the content and properties of nano-sized bioparticles with single-particle profiler.

Author

Sych T, Schlegel J, Barriga HMG, Ojansivu M, Hanke L, Weber F, Beklem Bostancioglu R, Ezzat K, Stangl H, Plochberger B, Laurencikiene J, El Andaloussi S, Fürth D, Stevens MM, and Sezgin E

Subjects
Particle Size, Liposomes chemistry, Nanoparticles chemistry
Abstract

We introduce a method, single-particle profiler, that provides single-particle information on the content and biophysical properties of thousands of particles in the size range 5-200 nm. We use our single-particle profiler to measure the messenger RNA encapsulation efficiency of lipid nanoparticles, the viral binding efficiencies of different nanobodies, and the biophysical heterogeneity of liposomes, lipoproteins, exosomes and viruses., (© 2023. The Author(s).)

Published
2024
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47. Transcriptomic and proteomic profiles of fetal versus adult mesenchymal stromal cells and mesenchymal stromal cell-derived extracellular vesicles.

Author

Gençer EB, Lor YK, Abomaray F, El Andaloussi S, Pernemalm M, Sharma N, Hagey DW, Görgens A, Gustafsson MO, Le Blanc K, Asad Toonsi M, Walther-Jallow L, and Götherström C

Subjects
Animals, Transcriptome, Proteomics, Gene Expression Profiling, Mesenchymal Stem Cells metabolism, Extracellular Vesicles metabolism
Abstract

Background: Mesenchymal stem/stromal cells (MSCs) can regenerate tissues through engraftment and differentiation but also via paracrine signalling via extracellular vesicles (EVs). Fetal-derived MSCs (fMSCs) have been shown, both in vitro and in animal studies, to be more efficient than adult MSC (aMSCs) in generating bone and muscle but the underlying reason for this difference has not yet been clearly elucidated. In this study, we aimed to systematically investigate the differences between fetal and adult MSCs and MSC-derived EVs at the phenotypic, RNA, and protein levels., Methods: We carried out a detailed and comparative characterization of culture-expanded fetal liver derived MSCs (fMSCs) and adult bone marrow derived MSCs (aMSCs) phenotypically, and the MSCs and MSC-derived EVs were analysed using transcriptomics and proteomics approaches with RNA Sequencing and Mass Spectrometry., Results: Fetal MSCs were smaller, exhibited increased proliferation and colony-forming capacity, delayed onset of senescence, and demonstrated superior osteoblast differentiation capability compared to their adult counterparts. Gene Ontology analysis revealed that fMSCs displayed upregulated gene sets such as "Positive regulation of stem cell populations", "Maintenance of stemness" and "Muscle cell development/contraction/Myogenesis" in comparison to aMSCs. Conversely, aMSCs displayed upregulated gene sets such as "Complement cascade", "Adipogenesis", "Extracellular matrix glycoproteins" and "Cellular metabolism", and on the protein level, "Epithelial cell differentiation" pathways. Signalling entropy analysis suggested that fMSCs exhibit higher signalling promiscuity and hence, higher potency than aMSCs. Gene ontology comparisons revealed that fetal MSC-derived EVs (fEVs) were enriched for "Collagen fibril organization", "Protein folding", and "Response to transforming growth factor beta" compared to adult MSC-derived EVs (aEVs), whereas no significant difference in protein expression in aEVs compared to fEVs could be detected., Conclusions: This study provides detailed and systematic insight into the differences between fMSCs and aMSCs, and MSC-derived EVs. The key finding across phenotypic, transcriptomic and proteomic levels is that fMSCs exhibit higher potency than aMSCs, meaning they are in a more undifferentiated state. Additionally, fMSCs and fMSC-derived EVs may possess greater bone forming capacity compared to aMSCs. Therefore, using fMSCs may lead to better treatment efficacy, especially in musculoskeletal diseases., (© 2024. The Author(s).)

Published
2024
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48. Tumor cell derived osteopontin and prostaglandin E2 synergistically promote the expansion of myeloid derived suppressor cells during the tumor immune escape phase.

Author

Mamand DR, Bazaz S, Mohammad DK, Saher O, Wiklander OPB, Sadeghi B, Hassan M, El-Andaloussi S, and Abedi-Valugerdi M

Subjects
Animals, Mice, Dinoprostone metabolism, Osteopontin metabolism, Pioglitazone, Tumor Escape, Myeloid-Derived Suppressor Cells
Abstract

The immune escape stage in cancer immunoediting is a pivotal feature, transitioning immune-controlled tumor dormancy to progression, and augmenting invasion and metastasis. Tumors employ diverse mechanisms for immune escape, with generating immunosuppressive cells from skewed hematopoiesis being a crucial mechanism. This led us to suggest that tumor cells with immune escape properties produce factors that induce dysregulations in hematopoiesis. In support of this suggestion, this study found that mice bearing advanced-stage tumors exhibited dysregulated hematopoiesis characterized by the development of splenomegaly, anemia, extramedullary hematopoiesis, production of immunosuppressive mediators, and expanded medullary myelopoiesis. Further ex vivo studies exhibited that conditioned medium derived from EL4lu2 cells could mediate the expansion of myeloid derived suppressor cells (MDSCs) in bone marrow cell cultures. The protein array profiling results revealed the presence of elevated levels of osteopontin (OPN), prostaglandin E2 (PGE2) and interleukin 17 (IL-17) in the culture medium derived from EL4luc2 cells. Accordingly, substantial levels of these factors were also detected in the sera of mice bearing EL4luc2 tumors. Among these factors, only PGE2 alone could increase the number of MDSCs in the BM cell cultures. This effect of PGE2 was significantly potentiated by the presence of OPN but not IL-17. Finally, in vitro treatment of EL4luc2 cells with pioglitazone, a modulator of OPN and cyclooxygenase 2 (COX-2) resulted in a significant reduction in cell proliferation in EL4luc2 cells. Our findings highlight the significant role played by tumor cell-derived OPN and PGE2 in fostering the expansion of medullary MDSCs and in promoting tumor cell proliferation. Furthermore, these intertwined cancer processes could be key targets for pioglitazone intervention., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Published
2024
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49. Size matters: Functional differences of small extracellular vesicle subpopulations in cardiac repair responses.

Author

van de Wakker SI, Bauzá-Martinez J, Ríos Arceo C, Manjikian H, Snijders Blok CJB, Roefs MT, Willms E, Maas RGC, Pronker MF, de Jong OG, Wu W, Görgens A, El Andaloussi S, Sluijter JPG, and Vader P

Subjects
Biological Assay, Chromatography, Gel, Extracellular Vesicles
Abstract

Cardiac progenitor cell (CPC)-derived small extracellular vesicles (sEVs) exhibit great potential to stimulate cardiac repair. However, the multifaceted nature of sEV heterogeneity presents a challenge in understanding the distinct mechanisms underlying their regenerative abilities. Here, a dual-step multimodal flowthrough and size-exclusion chromatography method was applied to isolate and separate CPC-derived sEV subpopulations to study the functional differences related to cardiac repair responses. Three distinct sEV subpopulations were identified with unique protein profiles. Functional cell assays for cardiac repair-related processes demonstrated that the middle-sized and smallest-sized sEV subpopulations exhibited the highest pro-angiogenic and anti-fibrotic activities. Proteasome activity was uniquely seen in the smallest-sized subpopulation. The largest-sized subpopulation showed no effect in any of the functional assays. This research uncovers the existence of sEV subpopulations, each characterized by a distinct composition and biological function. Enhancing our understanding of sEV heterogeneity will provide valuable insights into sEV mechanisms of action, ultimately accelerating the translation of sEV therapeutics., (© 2024 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.)

Published
2024
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50. Modulation of Pro-Inflammatory IL-6 Trans-Signaling Axis by Splice Switching Oligonucleotides as a Therapeutic Modality in Inflammation.

Author

Gupta D, Orehek S, Turunen J, O'Donovan L, Gait MJ, El-Andaloussi S, and Wood MJA

Subjects
Animals, Mice, Cytokine Receptor gp130, Inflammation, Oligonucleotides, Interleukin-6, Cytokines
Abstract

Interleukin-6 (IL-6) is a pleiotropic cytokine that plays a crucial role in maintaining normal homeostatic processes under the pathogenesis of various inflammatory and autoimmune diseases. This context-dependent effect from a cytokine is due to two distinctive forms of signaling: cis -signaling and trans-signaling . IL-6 cis-signaling involves binding IL-6 to the membrane-bound IL-6 receptor and Glycoprotein 130 (GP130) signal-transducing subunit. By contrast, in IL-6 trans-signaling , complexes of IL-6 and the soluble form of the IL-6 receptor (sIL-6R) signal via membrane-bound GP130. Various strategies have been employed in the past decade to target the pro-inflammatory effect of IL-6 in numerous inflammatory disorders. However, their development has been hindered since these approaches generally target global IL-6 signaling, also affecting the anti-inflammatory effects of IL-6 signaling too. Therefore, novel strategies explicitly targeting the pro-inflammatory IL-6 trans-signaling without affecting the IL-6 cis-signaling are required and carry immense therapeutic potential. Here, we have developed a novel approach to specifically decoy IL-6-mediated trans-signaling by modulating alternative splicing in GP130 , an IL-6 signal transducer, by employing splice switching oligonucleotides (SSO), to induce the expression of truncated soluble isoforms of the protein GP130. This isoform is devoid of signaling domains but allows for specifically sequestering the IL-6/sIL-6R receptor complex with high affinity in serum and thereby suppressing inflammation. Using the state-of-the-art Pip6a cell-penetrating peptide conjugated to PMO-based SSO targeting GP130 for efficient in vivo delivery, reduced disease phenotypes in two different inflammatory mouse models of systemic and intestinal inflammation were observed. Overall, this novel gene therapy platform holds great potential as a refined therapeutic intervention for chronic inflammatory diseases.

Published
2023
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