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1. The Cervical and Meningeal Lymphatic Network as a Pathway for Retrograde Nanoparticle Transport to the Brain

Author

Ramos-Zaldívar HM, Polakovicova I, Salas-Huenuleo E, Yefi CP, Silva-Ancahuail D, Jara-Guajardo P, Oyarzún JE, Neira-Troncoso Á, Burgos PV, Cavieres VA, Arias-Muñoz E, Martínez C, Riveros AL, Corvalán AH, Kogan MJ, and Andia ME

Subjects
extracellular vesicles, spions, gold nanorods, chinese ink, meningeal lymphatic vessels, nanomedicine, Medicine (General), R5-920
Abstract

Héctor M Ramos-Zaldívar,1 Iva Polakovicova2,3 ,† Edison Salas-Huenuleo,4 Claudia P Yefi,5 David Silva-Ancahuail,2,6 Pedro Jara-Guajardo,2,6 Juan Esteban Oyarzún,7,8 Álvaro Neira-Troncoso,3,9 Patricia V Burgos,9 Viviana A Cavieres,9 Eloísa Arias-Muñoz,9 Carlos Martínez,10 Ana L Riveros,2,6 Alejandro H Corvalán,2,3 Marcelo J Kogan,2,6 Marcelo E Andia7,8 1Doctoral Program in Medical Sciences, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile; 2Advanced Center for Chronic Diseases (ACCDiS), Santiago, Chile; 3Department of Hematology and Oncology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile; 4Advanced Integrated Technologies SpA, (AINTECH), Santiago, Chile; 5Escuela de Medicina Veterinaria, Facultad de Ciencias de la Naturaleza, Universidad San Sebastián, Santiago, Chile; 6Departamento de Química Farmacológica y Toxicológica, Facultad de Ciencias Químicas y Farmacéuticas, Laboratorio de Nanobiotecnología, Universidad de Chile, Santiago, Chile; 7Millennium Institute for Intelligent Healthcare Engineering, Santiago, Chile; 8Biomedical Imaging Center, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile; 9Centro de Biología Celular y Biomedicina (CEBICEM), Facultad de Medicina y Ciencia, Universidad San Sebastián, Santiago, Chile; 10Experimental Surgery and Simulation Center, Department of Digestive Surgery, Clinic Hospital, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile†Iva Polakovicova passed away on October 12, 2020Correspondence: Héctor M Ramos-Zaldívar, Email hmramos@uc.clIntroduction: The meningeal lymphatic vessels have been described as a pathway that transports cerebrospinal fluid and interstitial fluid in a unidirectional manner towards the deep cervical lymph nodes. However, these vessels exhibit anatomical and molecular characteristics typical of initial lymphatic vessels, with the absence of surrounding smooth muscle and few or absent valves. Given its structure, this network could theoretically allow for bidirectional motion. Nevertheless, it has not been assessed as a potential route for nanoparticles to travel from peripheral tissues to the brain.Methods: We employed superparamagnetic iron oxide nanoparticles (SPIONs), exosomes loaded with SPIONs, gold nanorods, and Chinese ink nanoparticles. SPIONs were prepared via chemical coprecipitation, while exosomes were isolated from the B16F10 melanoma cell line through the Exo-Spin column protocol and loaded with SPIONs through electroporation. Gold nanorods were functionalized with polyethylene glycol. We utilized C57BL/6 mice for post-mortem and in vivo procedures. To evaluate the retrograde directional flow, we injected each nanoparticle solution in the deep cervical lymph node. The head and neck were fixed for magnetic resonance imaging and histological analysis.Results: Here we show that extracellular vesicles derived from the B16F10 melanoma cell line, along with superparamagnetic iron oxide nanoparticles, gold nanorods, and Chinese ink nanoparticles can reach the meningeal lymphatic vessels and the brain of C57BL/6 mice after administration within the deep cervical lymph nodes post-mortem and in vivo, exclusively through lymphatic structures.Discussion: The functional anatomy of dural lymphatics has been found to be conserved between mice and humans, suggesting that our findings may have significant implications for advancing targeted drug delivery systems using nanoparticles. Understanding the retrograde transport of nanoparticles through the meningeal lymphatic network could lead to novel therapeutic approaches in nanomedicine, offering new insights into fluid dynamics in both physiological and neuropathological contexts. Further research into this pathway may unlock new strategies for treating neurological diseases or enhancing drug delivery to the brain.Keywords: extracellular vesicles, SPIONs, gold nanorods, Chinese ink, meningeal lymphatic vessels, nanomedicine

Published
2024

3. 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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4. 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, KW, Aikawa, E, Jose Alcaraz, M, Anderson, JD, Andriantsitohaina, R, Antoniou, A, Arab, T, Archer, F, Atkin-Smith, GK, Ayre, DC, Bach, J-M, Bachurski, D, Baharvand, H, Balaj, L, Baldacchino, S, Bauer, NN, Baxter, AA, Bebawy, M, Beckham, C, Zavec, AB, Benmoussa, A, Berardi, AC, Bergese, P, Bielska, E, Blenkiron, C, Bobis-Wozowicz, S, Boilard, E, Boireau, W, Bongiovanni, A, Borras, FE, Bosch, S, Boulanger, CM, Breakefield, X, Breglio, AM, Brennan, MA, Brigstock, DR, Brisson, A, Broekman, MLD, Bromberg, JF, Bryl-Gorecka, P, Buch, S, Buck, AH, Burger, D, Busatto, S, Buschmann, D, Bussolati, B, Buzas, E, Byrd, JB, Camussi, G, Carter, DRF, Caruso, S, Chamley, LW, Chang, Y-T, 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, Chaudhuri, AD, de Candia, P, De Santana Junior, 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, F, Duncan, HM, Eichenberger, RM, Ekstrom, K, Andaloussi, SEL, Elie-Caille, C, Erdbrugger, U, Falcon-Perez, JM, Fatima, F, Fish, JE, Flores-Bellver, M, Forsonits, A, Frelet-Barrand, A, Fricke, F, Fuhrmann, G, Gabrielsson, S, Gamez-Valero, A, Gardiner, C, Gaertner, K, Gaudin, R, Gho, YS, Giebel, B, Gilbert, C, Gimona, M, Giusti, I, Goberdhan, DC, Goergens, A, Gorski, SM, Greening, DW, Gross, JC, Gualerzi, A, Gupta, GN, Gustafson, D, Handberg, A, Haraszti, RA, Harrison, P, Hegyesi, H, Hendrix, A, Hill, AF, Hochberg, FH, Hoffmann, KF, Holder, B, Holthofer, H, Hosseinkhani, B, Hu, G, Huang, Y, Huber, V, Hunt, S, Ibrahim, AG-E, Ikezu, T, Inal, JM, Isin, M, Ivanova, A, Jackson, HK, Jacobsen, S, Jay, SM, Jayachandran, M, Jenster, G, Jiang, L, Johnson, SM, Jones, JC, Jong, A, Jovanovic-Talisman, T, Jung, S, Kalluri, R, Kano, S-I, Kaur, S, Kawamura, Y, Keller, ET, Khamari, D, Khomyakova, E, Khvorova, A, Kierulf, P, Kim, KP, Kislinger, T, Klingeborn, M, Klinke, DJ, Kornek, M, Kosanovic, MM, Kovacs, AF, Kraemer-Albers, E-M, Krasemann, S, Krause, M, Kurochkin, I, Kusuma, GD, Kuypers, S, Laitinen, S, Langevin, SM, Languino, LR, Lannigan, J, Lasser, C, Laurent, LC, Lavieu, G, Lazaro-Ibanez, E, Le Lay, S, Lee, M-S, Lee, YXF, Lemos, DS, Lenassi, M, Leszczynska, A, Li, ITS, Liao, K, Libregts, SF, Ligeti, E, Lim, R, Lim, SK, Line, A, Linnemannstoens, K, Llorente, A, Lombard, CA, Lorenowicz, MJ, Lorincz, AM, Lotvall, J, Lovett, J, Lowry, MC, Loyer, X, Lu, Q, Lukomska, B, Lunavat, TR, Maas, SLN, Malhi, H, Marcilla, A, Mariani, J, Mariscal, J, Martens-Uzunova, ES, Martin-Jaular, L, Martinez, MC, Martins, VR, Mathieu, M, Mathivanan, S, Maugeri, M, McGinnis, LK, McVey, MJ, Meckes, DG, Meehan, KL, Mertens, I, Minciacchi, VR, Moller, A, Jorgensen, MM, Morales-Kastresana, A, Morhayim, J, Mullier, F, Muraca, M, Musante, L, Mussack, V, Muth, DC, Myburgh, KH, Najrana, T, Nawaz, M, Nazarenko, I, Nejsum, P, Neri, C, Neri, T, Nieuwland, R, Nimrichter, L, Nolan, JP, Nolte-'t Hoen, ENM, Noren Hooten, N, O'Driscoll, L, O'Grady, T, O'Loghlen, A, Ochiya, T, Olivier, M, Ortiz, A, Ortiz, LA, Osteikoetxea, X, Ostegaard, O, Ostrowski, M, Park, J, Pegtel, DM, Peinado, H, Perut, F, Pfaffl, MW, Phinney, DG, Pieters, BCH, Pink, RC, Pisetsky, DS, von Strandmann, EP, Polakovicova, I, Poon, IKH, Powell, BH, Prada, I, Pulliam, L, Quesenberry, P, Radeghieri, A, Raffai, RL, Raimondo, S, Rak, J, Ramirez, M, Raposo, G, Rayyan, MS, Regev-Rudzki, N, Ricklefs, FL, Robbins, PD, Roberts, DD, Rodrigues, SC, Rohde, E, Rome, S, Rouschop, KMA, Rughetti, A, Russell, AE, Saa, P, Sahoo, S, Salas-Huenuleo, E, Sanchez, C, Saugstad, JA, Saul, MJ, Schiffelers, RM, Schneider, R, Schoyen, TH, Scott, A, Shahaj, E, Sharma, S, Shatnyeva, O, Shekari, F, Shelke, GV, Shetty, AK, Shiba, K, Siljander, PR-M, Silva, AM, Skowronek, A, Snyder, OL, Soares, RP, Sodar, BW, Soekmadji, C, Sotillo, J, Stahl, PD, Stoorvogel, W, Stott, SL, Strasser, EF, Swift, S, Tahara, H, Tewari, M, Timms, K, Tiwari, S, Tixeira, R, Tkach, M, Toh, WS, Tomasini, R, Torrecilhas, AC, Pablo Tosar, J, Toxavidis, V, Urbanelli, L, Vader, P, van Balkom, BWM, van der Grein, SG, Van Deun, J, van Herwijnen, MJC, Van Keuren-Jensen, K, van Niel, G, van Royen, ME, van Wijnen, AJ, Helena Vasconcelos, M, Vechetti, IJ, Veit, TD, Vella, LJ, Velot, E, Verweij, FJ, Vestad, B, Vinas, JL, Visnovitz, T, Vukman, KV, Wahlgren, J, Watson, DC, Wauben, MHM, Weaver, A, Webber, JP, Weber, V, Wehman, AM, Weiss, DJ, Welsh, JA, Wendt, S, Wheelock, AM, 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, AR, Zickler, AM, Zimmermann, P, Zivkovic, AM, Zocco, D, Zuba-Surma, EK, Thery, C, Witwer, KW, Aikawa, E, Jose Alcaraz, M, Anderson, JD, Andriantsitohaina, R, Antoniou, A, Arab, T, Archer, F, Atkin-Smith, GK, Ayre, DC, Bach, J-M, Bachurski, D, Baharvand, H, Balaj, L, Baldacchino, S, Bauer, NN, Baxter, AA, Bebawy, M, Beckham, C, Zavec, AB, Benmoussa, A, Berardi, AC, Bergese, P, Bielska, E, Blenkiron, C, Bobis-Wozowicz, S, Boilard, E, Boireau, W, Bongiovanni, A, Borras, FE, Bosch, S, Boulanger, CM, Breakefield, X, Breglio, AM, Brennan, MA, Brigstock, DR, Brisson, A, Broekman, MLD, Bromberg, JF, Bryl-Gorecka, P, Buch, S, Buck, AH, Burger, D, Busatto, S, Buschmann, D, Bussolati, B, Buzas, E, Byrd, JB, Camussi, G, Carter, DRF, Caruso, S, Chamley, LW, Chang, Y-T, 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, Chaudhuri, AD, de Candia, P, De Santana Junior, 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, F, Duncan, HM, Eichenberger, RM, Ekstrom, K, Andaloussi, SEL, Elie-Caille, C, Erdbrugger, U, Falcon-Perez, JM, Fatima, F, Fish, JE, Flores-Bellver, M, Forsonits, A, Frelet-Barrand, A, Fricke, F, Fuhrmann, G, Gabrielsson, S, Gamez-Valero, A, Gardiner, C, Gaertner, K, Gaudin, R, Gho, YS, Giebel, B, Gilbert, C, Gimona, M, Giusti, I, Goberdhan, DC, Goergens, A, Gorski, SM, Greening, DW, Gross, JC, Gualerzi, A, Gupta, GN, Gustafson, D, Handberg, A, Haraszti, RA, Harrison, P, Hegyesi, H, Hendrix, A, Hill, AF, Hochberg, FH, Hoffmann, KF, Holder, B, Holthofer, H, Hosseinkhani, B, Hu, G, Huang, Y, Huber, V, Hunt, S, Ibrahim, AG-E, Ikezu, T, Inal, JM, Isin, M, Ivanova, A, Jackson, HK, Jacobsen, S, Jay, SM, Jayachandran, M, Jenster, G, Jiang, L, Johnson, SM, Jones, JC, Jong, A, Jovanovic-Talisman, T, Jung, S, Kalluri, R, Kano, S-I, Kaur, S, Kawamura, Y, Keller, ET, Khamari, D, Khomyakova, E, Khvorova, A, Kierulf, P, Kim, KP, Kislinger, T, Klingeborn, M, Klinke, DJ, Kornek, M, Kosanovic, MM, Kovacs, AF, Kraemer-Albers, E-M, Krasemann, S, Krause, M, Kurochkin, I, Kusuma, GD, Kuypers, S, Laitinen, S, Langevin, SM, Languino, LR, Lannigan, J, Lasser, C, Laurent, LC, Lavieu, G, Lazaro-Ibanez, E, Le Lay, S, Lee, M-S, Lee, YXF, Lemos, DS, Lenassi, M, Leszczynska, A, Li, ITS, Liao, K, Libregts, SF, Ligeti, E, Lim, R, Lim, SK, Line, A, Linnemannstoens, K, Llorente, A, Lombard, CA, Lorenowicz, MJ, Lorincz, AM, Lotvall, J, Lovett, J, Lowry, MC, Loyer, X, Lu, Q, Lukomska, B, Lunavat, TR, Maas, SLN, Malhi, H, Marcilla, A, Mariani, J, Mariscal, J, Martens-Uzunova, ES, Martin-Jaular, L, Martinez, MC, Martins, VR, Mathieu, M, Mathivanan, S, Maugeri, M, McGinnis, LK, McVey, MJ, Meckes, DG, Meehan, KL, Mertens, I, Minciacchi, VR, Moller, A, Jorgensen, MM, Morales-Kastresana, A, Morhayim, J, Mullier, F, Muraca, M, Musante, L, Mussack, V, Muth, DC, Myburgh, KH, Najrana, T, Nawaz, M, Nazarenko, I, Nejsum, P, Neri, C, Neri, T, Nieuwland, R, Nimrichter, L, Nolan, JP, Nolte-'t Hoen, ENM, Noren Hooten, N, O'Driscoll, L, O'Grady, T, O'Loghlen, A, Ochiya, T, Olivier, M, Ortiz, A, Ortiz, LA, Osteikoetxea, X, Ostegaard, O, Ostrowski, M, Park, J, Pegtel, DM, Peinado, H, Perut, F, Pfaffl, MW, Phinney, DG, Pieters, BCH, Pink, RC, Pisetsky, DS, von Strandmann, EP, Polakovicova, I, Poon, IKH, Powell, BH, Prada, I, Pulliam, L, Quesenberry, P, Radeghieri, A, Raffai, RL, Raimondo, S, Rak, J, Ramirez, M, Raposo, G, Rayyan, MS, Regev-Rudzki, N, Ricklefs, FL, Robbins, PD, Roberts, DD, Rodrigues, SC, Rohde, E, Rome, S, Rouschop, KMA, Rughetti, A, Russell, AE, Saa, P, Sahoo, S, Salas-Huenuleo, E, Sanchez, C, Saugstad, JA, Saul, MJ, Schiffelers, RM, Schneider, R, Schoyen, TH, Scott, A, Shahaj, E, Sharma, S, Shatnyeva, O, Shekari, F, Shelke, GV, Shetty, AK, Shiba, K, Siljander, PR-M, Silva, AM, Skowronek, A, Snyder, OL, Soares, RP, Sodar, BW, Soekmadji, C, Sotillo, J, Stahl, PD, Stoorvogel, W, Stott, SL, Strasser, EF, Swift, S, Tahara, H, Tewari, M, Timms, K, Tiwari, S, Tixeira, R, Tkach, M, Toh, WS, Tomasini, R, Torrecilhas, AC, Pablo Tosar, J, Toxavidis, V, Urbanelli, L, Vader, P, van Balkom, BWM, van der Grein, SG, Van Deun, J, van Herwijnen, MJC, Van Keuren-Jensen, K, van Niel, G, van Royen, ME, van Wijnen, AJ, Helena Vasconcelos, M, Vechetti, IJ, Veit, TD, Vella, LJ, Velot, E, Verweij, FJ, Vestad, B, Vinas, JL, Visnovitz, T, Vukman, KV, Wahlgren, J, Watson, DC, Wauben, MHM, Weaver, A, Webber, JP, Weber, V, Wehman, AM, Weiss, DJ, Welsh, JA, Wendt, S, Wheelock, AM, 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, AR, Zickler, AM, Zimmermann, P, Zivkovic, AM, Zocco, D, and Zuba-Surma, EK

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

5. 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
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6. SAFETY AND EFFICACY OF THYMIC PEPTIDES IN THE TREATMENT OF HOSPITALIZED COVID-19 PATIENTS IN HONDURAS.

Author

Ramos-Zaldívar H, Reyes-Perdomo K, Espinoza-Moreno N, Dox-Cruz E, Urbina T, Caballero A, Dominguez E, Calix S, Monterroso-Reyes J, Vásquez E, Ortiz T, Rodríguez-Machado H, Solis M, Silva I, Galeano M, Alvarado A, Medina A, Guerrero-Díaz L, Jiménez-Faraj J, Santos C, Arita W, Montufar D, Sabillón J, Sorto M, Navarro X, Palomo-Bermúdez V, Andino H, Guzman S, Reyes M, Pazf E, Enamorado J, Sagastume Y, Rivera A, Sarmiento C, Pineda X, Puerto V, Landaverde J, Reyes S, Perdomo I, Rivera J, Girón W, Sabillón K, Leiva P, Toro K, Montes-Gambarelli J, Flores C, Salas-Huenuleo E, and Andia M

Subjects
Humans, Honduras, Kaplan-Meier Estimate, Proportional Hazards Models, Peptides adverse effects, COVID-19 Drug Treatment
Abstract

Coronavirus disease 2019 (Covid-19) active cases continue to demand the development of safe and effective treatments. This is the first clinical trial to evaluate the safety and efficacy of oral thymic peptides. ; We conducted a nonrandomized phase 2 trial with a historic control group to evaluate the safety and efficacy of a daily 250-mg oral dose of thymic peptides in the treatment of hospitalized Covid-19 patients. Comparisons based on standard care from registry data were performed after propensity score matching. The primary outcomes were survival, time to recovery, and number of participants with treatment-related adverse events or side effects by day 20. ; A total of 44 patients were analyzed in this study: 22 in the thymic peptide group and 22 in the standard care group. There were no deaths in the intervention group compared to 24% mortality in standard care by day 20 (log-rank P=0.02). Kaplan-Meier analysis showed a significantly shorter time to recovery by day 20 in the thymic peptide group than in the standard care group (median, 6 days vs. 12 days; hazard ratio for recovery, 2.75 [95% confidence interval, 1.34 to 5.62]; log-rank P=0.002). No side effects or adverse events were reported. ; In patients hospitalized with Covid-19, the use of thymic peptides resulted in no side effects, adverse events, or deaths by day 20. Compared with the registry data, a significantly shorter time to recovery and mortality reduction were measured.

Published
2022

7. Extracellular vesicles through the blood-brain barrier: a review.

Author

Ramos-Zaldívar HM, Polakovicova I, Salas-Huenuleo E, Corvalán AH, Kogan MJ, Yefi CP, and Andia ME

Subjects
Animals, Biological Transport, Mammals, Transcytosis, Zebrafish, Blood-Brain Barrier, Extracellular Vesicles metabolism
Abstract

Extracellular vesicles (EVs) are particles naturally released from cells that are delimited by a lipid bilayer and are unable to replicate. How the EVs cross the Blood-Brain barrier (BBB) in a bidirectional manner between the bloodstream and brain parenchyma remains poorly understood. Most in vitro models that have evaluated this event have relied on monolayer transwell or microfluidic organ-on-a-chip techniques that do not account for the combined effect of all cellular layers that constitute the BBB at different sites of the Central Nervous System. There has not been direct transcytosis visualization through the BBB in mammals in vivo, and evidence comes from in vivo experiments in zebrafish. Literature is scarce on this topic, and techniques describing the mechanisms of EVs motion through the BBB are inconsistent. This review will focus on in vitro and in vivo methodologies used to evaluate EVs transcytosis, how EVs overcome this fundamental structure, and discuss potential methodological approaches for future analyses to clarify these issues. Understanding how EVs cross the BBB will be essential for their future use as vehicles in pharmacology and therapeutics., (© 2022. The Author(s).)

Published
2022
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8. Peptide Targeted Gold Nanoplatform Carrying miR-145 Induces Antitumoral Effects in Ovarian Cancer Cells.

Author

Salas-Huenuleo E, Hernández A, Lobos-González L, Polakovičová I, Morales-Zavala F, Araya E, Celis F, Romero C, and Kogan MJ

Abstract

One of the recent attractive therapeutic approaches for cancer treatment is restoring downregulated microRNAs. They play an essential muti-regulatory role in cellular processes such as proliferation, differentiation, survival, apoptosis, cell cycle, angiogenesis, and metastasis, among others. In this study, a gold nanoplatform (GNPF) carrying miR-145, a downregulated microRNA in many cancer types, including epithelial ovarian cancer, was designed and synthesized. For targeting purposes, the GNPF was functionalized with the FSH33 peptide, which provided selectivity for ovarian cancer, and loaded with the miR-145 to obtain the nanosystem GNPF-miR-145. The GNPF-mir-145 was selectively incorporated in A2780 and SKOV3 cells and significantly inhibited cell viability and migration and exhibited proliferative and anchor-independent growth capacities. Moreover, it diminished VEGF release and reduced the spheroid size of ovarian cancer through the damage of cell membranes, thus decreasing cell viability and possibly activating apoptosis. These results provide important advances in developing miR-based therapies using nanoparticles as selective vectors and provide approaches for in vivo evaluation.

Published
2022
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9. Development of a Nanostructured Lipid Carrier (NLC) by a Low-Energy Method, Comparison of Release Kinetics and Molecular Dynamics Simulation.

Author

Ortiz AC, Yañez O, Salas-Huenuleo E, and Morales JO

Abstract

Lipid nanocarriers have a great potential for improving the physicochemical characteristics and behavior of poorly water-soluble drugs, such as aqueous dispersibility and oral bioavailability. This investigation presents a novel nanostructured lipid carrier (NLC) based on a mixture of solid lipid glycerides, fatty acid esters of PEG 1500 (Gelucire ® 44/14), and an oil mix composed of capric and caprylic triglycerides (Miglyol ® 812). These NLCs were developed by a simple low-energy method based on melt emulsification to yield highly encapsulating and narrowly distributed nanoparticles (~100 nm, PdI = 0.1, and zeta potential = ~-10 mV). Rhodamine 123 was selected as a poorly water-soluble drug model and owing to its spectroscopic properties. The novel NLCs were characterized by dynamic light scattering (DLS), zeta potential, nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), differential scanning calorimetry (DSC), and colloidal stability. The drug release was determined through a dialysis bag and vertical Franzs' cells to provide insights about the methods' suitability, revealing similar performance regardless of their different fluid dynamics. Rhodamine 123 followed a characteristic biphasic release profile owing to the swelling of the hydrophilic polymer coating and diffusion process from the lipid core as revealed by the Korsmeyers-Peppas kinetic modeling. Moreover, to elucidate the formation and incorporation of Rhodamine 123 into the NLC core, several molecular dynamics simulations were conducted. The temperature was shown to be an important condition to improve the formation of the nanoparticles. In addition, the liquid lipid incorporation to the formulation forms nanoparticles with imperfect centers, in contrast to nanoparticles without it. Moreover, Miglyol ® 812 improves hydrophobic molecule solubility. These results suggest the potential of novel NLC as a drug delivery system for poorly water-soluble drugs.

Published
2021
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10. Chitosan-Based Nanoparticles for Intracellular Delivery of ISAV Fusion Protein cDNA into Melanoma Cells: A Path to Develop Oncolytic Anticancer Therapies.

Author

Robles-Planells C, Sánchez-Guerrero G, Barrera-Avalos C, Matiacevich S, Rojo LE, Pavez J, Salas-Huenuleo E, Kogan MJ, Escobar A, Milla LA, Fernandez R, Imarai M, Spencer E, Huidobro-Toro JP, and Acuña-Castillo C

Subjects
Animals, Cell Line, Tumor, Cell Survival, Chitosan metabolism, DNA, Complementary metabolism, Giant Cells metabolism, Humans, Isavirus genetics, Lymphocytes cytology, Melanoma, Experimental, Mice, Mice, Inbred C57BL, Mice, Transgenic, Nanomedicine methods, Orthomyxoviridae Infections genetics, Recombinant Fusion Proteins chemistry, Surface Properties, Transfection, Antineoplastic Agents pharmacology, Chitosan chemistry, Melanoma drug therapy, Nanoparticles chemistry, Oncolytic Virotherapy methods, Skin Neoplasms drug therapy
Abstract

Oncolytic virus therapy has been tested against cancer in preclinical models and clinical assays. Current evidence shows that viruses induce cytopathic effects associated with fusogenic protein-mediated syncytium formation and immunogenic cell death of eukaryotic cells. We have previously demonstrated that tumor cell bodies generated from cells expressing the fusogenic protein of the infectious salmon anemia virus (ISAV-F) enhance crosspriming and display prophylactic antitumor activity against melanoma tumors. In this work, we evaluated the effects of the expression of ISAV-F on the B16 melanoma model, both in vitro and in vivo , using chitosan nanoparticles as transfection vehicle. We confirmed that the transfection of B16 tumor cells with chitosan nanoparticles (NP-ISAV) allows the expression of a fusogenically active ISAV-F protein and decreases cell viability because of syncytium formation in vitro . However, the in vivo transfection induces a delay in tumor growth, without inducing changes on the lymphoid populations in the tumor and the spleen. Altogether, our observations show that expression of ISAV fusion protein using chitosan nanoparticles induces cell fusion in melanoma cells and slight antitumor response., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Claudia Robles-Planells et al.)

Published
2020
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11. Gold nanoparticle based double-labeling of melanoma extracellular vesicles to determine the specificity of uptake by cells and preferential accumulation in small metastatic lung tumors.

Author

Lara P, Palma-Florez S, Salas-Huenuleo E, Polakovicova I, Guerrero S, Lobos-Gonzalez L, Campos A, Muñoz L, Jorquera-Cordero C, Varas-Godoy M, Cancino J, Arias E, Villegas J, Cruz LJ, Albericio F, Araya E, Corvalan AH, Quest AFG, and Kogan MJ

Subjects
Adenocarcinoma diagnostic imaging, Adenocarcinoma therapy, Animals, Antineoplastic Agents pharmacology, Cell Line, Tumor, Cell Membrane Permeability, Colonic Neoplasms diagnostic imaging, Colonic Neoplasms therapy, Fluorescent Dyes chemistry, Humans, Lung metabolism, Melanoma, Experimental diagnostic imaging, Melanoma, Experimental therapy, Mice, Mice, Inbred C57BL, Optical Imaging, Surface Properties, Tissue Distribution, Antineoplastic Agents chemistry, Extracellular Vesicles chemistry, Gold chemistry, Lung Neoplasms diagnostic imaging, Lung Neoplasms metabolism, Melanoma chemistry, Metal Nanoparticles chemistry
Abstract

Background: Extracellular vesicles (EVs) have shown great potential for targeted therapy, as they have a natural ability to pass through biological barriers and, depending on their origin, can preferentially accumulate at defined sites, including tumors. Analyzing the potential of EVs to target specific cells remains challenging, considering the unspecific binding of lipophilic tracers to other proteins, the limitations of fluorescence for deep tissue imaging and the effect of external labeling strategies on their natural tropism. In this work, we determined the cell-type specific tropism of B16F10-EVs towards cancer cell and metastatic tumors by using fluorescence analysis and quantitative gold labeling measurements. Surface functionalization of plasmonic gold nanoparticles was used to promote indirect labeling of EVs without affecting size distribution, polydispersity, surface charge, protein markers, cell uptake or in vivo biodistribution. Double-labeled EVs with gold and fluorescent dyes were injected into animals developing metastatic lung nodules and analyzed by fluorescence/computer tomography imaging, quantitative neutron activation analysis and gold-enhanced optical microscopy., Results: We determined that B16F10 cells preferentially take up their own EVs, when compared with colon adenocarcinoma, macrophage and kidney cell-derived EVs. In addition, we were able to detect the preferential accumulation of B16F10 EVs in small metastatic tumors located in lungs when compared with the rest of the organs, as well as their precise distribution between tumor vessels, alveolus and tumor nodules by histological analysis. Finally, we observed that tumor EVs can be used as effective vectors to increase gold nanoparticle delivery towards metastatic nodules., Conclusions: Our findings provide a valuable tool to study the distribution and interaction of EVs in mice and a novel strategy to improve the targeting of gold nanoparticles to cancer cells and metastatic nodules by using the natural properties of malignant EVs.

Published
2020
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12. Intranasal delivery of mesenchymal stem cell-derived exosomes reduces oxidative stress and markedly inhibits ethanol consumption and post-deprivation relapse drinking.

Author

Ezquer F, Quintanilla ME, Morales P, Santapau D, Ezquer M, Kogan MJ, Salas-Huenuleo E, Herrera-Marschitz M, and Israel Y

Subjects
Administration, Intranasal, Alcohol Drinking physiopathology, Amino Acid Transport System X-AG metabolism, Animals, Astrocytes physiology, Chronic Disease, Female, Hippocampus metabolism, Humans, Injections, Intraventricular, Microglia physiology, Nucleus Accumbens metabolism, Prefrontal Cortex metabolism, RNA, Messenger metabolism, Rats, Wistar, Secondary Prevention, Subcutaneous Fat cytology, Substance Withdrawal Syndrome prevention & control, Alcohol Drinking prevention & control, Exosomes transplantation, Mesenchymal Stem Cell Transplantation methods, Oxidative Stress physiology
Abstract

Chronic ethanol consumption leads to brain oxidative stress and neuroinflammation, conditions known to potentiate and perpetuate each other. Several studies have shown that neuroinflammation results in increases in chronic ethanol consumption. Recent reports showed that the intra-cerebroventricular administration of mesenchymal stem cells to rats consuming alcohol chronically markedly inhibited oxidative-stress, abolished neuroinflammation and greatly reduced chronic alcohol intake and post deprivation relapse-like alcohol intake. However, the intra-cerebroventricular administration of living cells is not suitable as a treatment of a chronic condition. The present study aimed at inhibiting ethanol intake by the non-invasive intranasal administration of human mesenchymal stem cell products: exosomes, microvesicles (40 to 150 nm) with marked antioxidant activity extruded from mesenchymal stem cells. The exosome membrane can fuse with the plasma membrane of cells in different tissues, thus delivering their content intracellularly. The study showed that the weekly intranasal administration of mesenchymal stem cell-derived exosomes to rats consuming alcohol chronically (1) inhibited their ethanol intake by 84 percent and blunted the relapse-like 'binge' drinking that follows an alcohol deprivation period and ethanol re-access. (2) Intranasally administered exosomes were found in the brain within 24 hours; (3) fully reversed both alcohol-induced hippocampal oxidative-stress, evidenced by a lower ratio of oxidized to reduced glutathione, and neuroinflammation, shown by a reduced astrocyte activation and microglial density; and (4) increased glutamate transporter GLT1 expression in nucleus accumbens, counteracting the inhibition of glutamate transporter activity, reportedly depressed under oxidative-stress conditions. Possible translational implications are envisaged., (© 2018 Society for the Study of Addiction.)

Published
2019
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13. The antinociceptive effect of resveratrol in bone cancer pain is inhibited by the Silent Information Regulator 1 inhibitor selisistat.

Author

Lux S, Lobos N, Lespay-Rebolledo C, Salas-Huenuleo E, Kogan MJ, Flores C, Pinto M, Hernandez A, Pelissier T, and Constandil L

Subjects
Animals, Behavior, Animal drug effects, Bone Neoplasms chemically induced, Cell Line, Tumor, Disease Models, Animal, Hyperalgesia prevention & control, Male, Mice, Mice, Inbred BALB C, Analgesics pharmacology, Bone Neoplasms pathology, Cancer Pain prevention & control, Carbazoles pharmacology, Resveratrol antagonists & inhibitors, Resveratrol pharmacology, Sirtuin 1 antagonists & inhibitors
Abstract

Objectives: To study the antinociceptive effect of single and repeated doses of resveratrol in a bone cancer pain model, and whether this effect is prevented by the Silent Information Regulator 1 (SIRT1) inhibitor selisistat., Methods: The femoral intercondylar bone of BALB/c mice was injected with 1 000 000 BJ3Z cancer cells. Bone resorption and tumour mass growth (measured by in vivo X-ray and fluorescence imaging), as well as mechanical nociceptive thresholds (von Frey device) and dynamic functionality (rotarod machine), were evaluated during the following 4 weeks. Acute resveratrol (100 mg/kg i.p.) and/or selisistat (10 mg/kg s.c.) were administered on day 14. Chronic resveratrol (100 mg/kg i.p., daily) and/or selisistat (0.5 μg/h s.c., Alzet pump) were administered between days 14 and 20., Key Findings: Tumour growth gradually incremented until day 31, while mechanical hyperalgesia started on day 3 after cancer cell injection. Acute resveratrol increased the mechanical threshold of pain (peaking at 1.5 h), while the dynamic functionality decreased. Chronic resveratrol produced a sustained antinociceptive effect on mechanical hyperalgesia and improved the loss of dynamic functionality induced by the bone cancer tumour. Selisistat prevented all the effects of resveratrol., Conclusions: Acute and chronic resveratrol induces antinociceptive effect in the model of metastatic osseous oncological pain, an effect that would be mediated by SIRT1 molecular signalling., (© 2018 Royal Pharmaceutical Society.)

Published
2019
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14. A New Kind of Quinonic-Antibiotic Useful Against Multidrug-Resistant S. aureus and E. faecium Infections.

Author

Campanini-Salinas J, Andrades-Lagos J, Gonzalez Rocha G, Choquesillo-Lazarte D, Bollo Dragnic S, Faúndez M, Alarcón P, Silva F, Vidal R, Salas-Huenuleo E, Kogan M, Mella J, Recabarren Gajardo G, and Vásquez-Velásquez D

Subjects
Anti-Bacterial Agents chemical synthesis, Chemical Phenomena, Humans, Microbial Sensitivity Tests, Models, Molecular, Molecular Structure, Structure-Activity Relationship, X-Ray Diffraction, Anti-Bacterial Agents chemistry, Anti-Bacterial Agents pharmacology, Drug Resistance, Multiple, Bacterial drug effects, Enterococcus faecium drug effects, Staphylococcus aureus drug effects
Abstract

A rapid emergence of resistant bacteria is occurring worldwide, endangering the efficacy of antibiotics and reducing the therapeutic arsenal available for treatment of infectious diseases. In the present study, we developed a new class of compounds with antibacterial activity obtained by a simple, two step synthesis and screened the products for in vitro antibacterial activity against ATCC ® strains using the broth microdilution method. The compounds exhibited minimum inhibitory concentrations (MIC) of 1⁻32 μg/mL against Gram-positive ATCC ® strains. The structure⁻activity relationship indicated that the thiophenol ring is essential for antibacterial activity and the substituents on the thiophenol ring module, for antibacterial activity. The most promising compounds detected by screening were tested against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VREF) clinical isolates. We found remarkable activity against VREF for compounds 7 and 16 , were the MIC 50/90 were 2/4 µg/mL and 4/4 µg/mL, respectively, while for vancomycin the MIC 50/90 was 256/512 µg/mL. Neither compound affected cell viability in any of the mammalian cell lines at any of the concentrations tested. These in vitro data show that compounds 7 and 16 have an interesting potential to be developed as new antibacterial drugs against infections caused by VREF.

Published
2018
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15. Stability of Antibacterial Silver Carboxylate Complexes against Staphylococcus epidermidis and Their Cytotoxic Effects.

Author

Aldabaldetrecu M, Tamayo L, Alarcon R, Walter M, Salas-Huenuleo E, Kogan MJ, Guerrero J, Paez M, and Azócar MI

Subjects
Aminosalicylic Acids chemistry, Animals, Anti-Bacterial Agents chemistry, Anti-Bacterial Agents pharmacology, Cell Line, Coordination Complexes chemistry, Coordination Complexes pharmacology, Drug Stability, Humans, Mice, Microbial Sensitivity Tests, Microscopy, Electron, Scanning, Microscopy, Electron, Transmission, Salicylates chemistry, Anti-Bacterial Agents chemical synthesis, Coordination Complexes chemical synthesis, Silver chemistry, Staphylococcus epidermidis drug effects
Abstract

The antibacterial effects against Staphylococcus epidermidis of five silver carboxylate complexes with anti-inflammatory ligands were studied in order to analyze and compare them in terms of stability (in solution and after exposure to UV light), and their antibacterial and morphological differences. Four effects of the Ag-complexes were evidenced by transmission electronic microscopy (TEM) and scanning electronic microscopy (SEM): DNA condensation, membrane disruption, shedding of cytoplasmic material and silver compound microcrystal penetration of bacteria. 5-Chlorosalicylic acid (5Cl) and sodium 4-aminosalicylate (4A) were the most effective ligands for synthesizing silver complexes with high levels of antibacterial activity. However, Ag-5Cl was the most stable against exposure UV light (365 nm). Cytotoxic effects were tested against two kinds of eukaryotic cells: murine fibroblast cells (T10 1/2) and human epithelial ovarian cancer cells (A2780). The main objective was to identify changes in their antibacterial properties associated with potential decomposition and the implications for clinical applications.

Published
2018
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16. Encapsulation of Gold Nanostructures and Oil-in-Water Nanocarriers in Microgels with Biomedical Potential.

Author

Inostroza-Riquelme M, Vivanco A, Lara P, Guerrero S, Salas-Huenuleo E, Chamorro A, Leyton L, Bolaños K, Araya E, Quest AFG, Kogan MJ, and Oyarzun-Ampuero F

Subjects
Antineoplastic Agents administration & dosage, Antineoplastic Agents chemistry, Cell Line, Tumor, Cell Survival drug effects, Curcumin administration & dosage, Curcumin chemistry, Drug Liberation, Emulsions, Gels, HEK293 Cells, Humans, Lasers, Particle Size, Photochemotherapy methods, Polyethylene Glycols chemistry, Solubility, Surface Properties, Drug Carriers chemistry, Gold chemistry, Nanospheres chemistry, Nanotubes chemistry
Abstract

Here we report the incorporation of gold nanostructures (nanospheres or nanorods, functionalized with carboxylate-end PEG) and curcumin oil-in-water (O/W) nanoemulsions (CurNem) into alginate microgels using the dripping technique. While gold nanostructures are promising nanomaterials for photothermal therapy applications, CurNem possess important pharmacological activities as reported here. In this sense, we evaluated the effect of CurNem on cell viability of both cancerous and non-cancerous cell lines (AGS and HEK293T, respectively), demonstrating preferential toxicity in cancer cells and safety for the non-cancerous cells. After incorporating gold nanostructures and CurNem together into the microgels, microstructures with diameters of 220 and 540 µm were obtained. When stimulating microgels with a laser, the plasmon effect promoted a significant rise in the temperature of the medium; the temperature increase was higher for those containing gold nanorods (11⁻12 °C) than nanospheres (1⁻2 °C). Interestingly, the incorporation of both nanosystems in the microgels maintains the photothermal properties of the gold nanostructures unmodified and retains with high efficiency the curcumin nanocarriers. We conclude that these results will be of interest to design hydrogel formulations with therapeutic applications.

Published
2018
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17. Improving gold nanorod delivery to the central nervous system by conjugation to the shuttle Angiopep-2.

Author

Velasco-Aguirre C, Morales-Zavala F, Salas-Huenuleo E, Gallardo-Toledo E, Andonie O, Muñoz L, Rojas X, Acosta G, Sánchez-Navarro M, Giralt E, Araya E, Albericio F, and Kogan MJ

Subjects
Animals, Biological Transport, Blood-Brain Barrier metabolism, Brain metabolism, Cell Survival, Drug Carriers chemistry, Drug Liberation, Endothelial Cells, Fluorescent Dyes chemistry, Humans, Male, Microscopy, Electron, Transmission methods, Optical Imaging methods, Particle Size, Peptides toxicity, Permeability, Polyethylene Glycols chemistry, Rats, Rats, Sprague-Dawley, Surface Properties, Tissue Distribution, Central Nervous System drug effects, Gold chemistry, Nanotubes chemistry, Peptides chemistry, Peptides pharmacology
Abstract

Aim: To improve the in vivo delivery of gold nanorods (GNRs) to the central nervous system of rats, these gold nanoparticles were conjugated to Angiopep-2, a shuttle peptide that can cross the blood-brain barrier., Materials & Methods: GNRs were synthesized and modified using polyethylene glycol and Angiopep-2 (GNR-PEG-Angiopep-2). The physicochemical properties, in vitro cytotoxicity and ex vivo biodistribution of the conjugate were examined., Results: GNR-PEG-Angiopep-2 was stable over the following days, and the different concentrations that were tested did not affect the viability of microvascular endothelial cells. The conjugation of Angiopep-2 to GNRs enhanced the endocytosis of these particles (in vitro) and the accumulation in brains (in vivo), when compared with GNRs modified only with PEG., Conclusion: This study provides evidence that Angiopep-2 improves the delivery of GNRs to the brain parenchyma. This property is highly relevant for future applications of GNRs as platforms for photothermal and theranostic purposes.

Published
2017
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