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2. Association between Bone Turnover Markers and Fracture Healing in Long Bone Non-Union: A Systematic Review.

Author

Perut, Francesca, Roncuzzi, Laura, Gómez-Barrena, Enrique, and Baldini, Nicola

Subjects
*FRACTURE healing, *BONE remodeling, *BONE fractures, *HEALING, *CINAHL database, *GENETIC disorders
Abstract

Background: Fracture healing is a very complex and well-orchestrated regenerative process involving many cell types and molecular pathways. Despite the high efficiency of this process, unsatisfying healing outcomes, such as non-union, occur for approximately 5–10% of long bone fractures. Although there is an obvious need to identify markers to monitor the healing process and to predict a potential failure in callus formation to heal the fracture, circulating bone turnover markers' (BTMs) utility as biomarkers in association with radiographic and clinical examination still lacks evidence so far. Methods: A systematic review on the association between BTMs changes and fracture healing in long bone non-union was performed following PRISMA guidelines. The research papers were identified via the PubMed, Cochrane, Cinahl, Web of Science, Scopus, and Embase databases. Studies in which the failure of fracture healing was associated with osteoporosis or genetic disorders were not included. Results: A total of 172 studies were collected and, given the inclusion criteria, 14 manuscripts were included in this review. Changes in circulating BTMs levels were detected during the healing process and across groups (healed vs. non-union patients and healthy vs. patients with non-union). However, we found high heterogeneity in patients' characteristics (fracture site, gender, and age) and in sample scheduling, which made it impossible to perform a meta-analysis. Conclusions: Clinical findings and radiographic features remain the two important components of non-union diagnosis so far. We suggest improving blood sample standardization and clinical data collection in future research to lay the foundations for the effective use of BTMs as tools for diagnosing non-union. [ABSTRACT FROM AUTHOR]

Published
2024
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3. Cell culture‐derived extracellular vesicles: Considerations for reporting cell culturing parameters

Author

Shekari, Faezeh, primary, Alibhai, Faisal J., additional, Baharvand, Hossein, additional, Börger, Verena, additional, Bruno, Stefania, additional, Davies, Owen, additional, Giebel, Bernd, additional, Gimona, Mario, additional, Salekdeh, Ghasem Hosseini, additional, Martin‐Jaular, Lorena, additional, Mathivanan, Suresh, additional, Nelissen, Inge, additional, Nolte‐’t Hoen, Esther, additional, O'Driscoll, Lorraine, additional, Perut, Francesca, additional, Pluchino, Stefano, additional, Pocsfalvi, Gabriella, additional, Salomon, Carlos, additional, Soekmadji, Carolina, additional, Staubach, Simon, additional, Torrecilhas, Ana Claudia, additional, Shelke, Ganesh Vilas, additional, Tertel, Tobias, additional, Zhu, Dandan, additional, Théry, Clotilde, additional, Witwer, Kenneth, additional, and Nieuwland, Rienk, additional

Published
2023
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10. The Release of Inflammatory Mediators from Acid-Stimulated Mesenchymal Stromal Cells Favours Tumour Invasiveness and Metastasis in Osteosarcoma

Author

Avnet, Sofia, primary, Lemma, Silvia, additional, Cortini, Margherita, additional, Di Pompo, Gemma, additional, Perut, Francesca, additional, Lipreri, Maria Veronica, additional, Roncuzzi, Laura, additional, Columbaro, Marta, additional, Errani, Costantino, additional, Longhi, Alessandra, additional, Zini, Nicoletta, additional, Heymann, Dominique, additional, Dominici, Massimo, additional, Grisendi, Giulia, additional, Golinelli, Giulia, additional, Consolino, Lorena, additional, Longo, Dario Livio, additional, Nanni, Cristina, additional, Righi, Alberto, additional, and Baldini, Nicola, additional

Published
2021
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11. Sarcoma treatment in the era of molecular medicine

Author

Grünewald, Thomas G. P., Alonso, Marta, Avnet, Sofia, Banito, Ana, Burdach, Stefan, Cidre-Aranaz, Florencia, Di Pompo, Gemma, Distel, Martin, Dorado-Garcia, Heathcliff, Garcia-Castro, Javier, Gonzalez-Gonzalez, Laura, Grigoriadis, Agamemnon E., Kasan, Merve, Koelsche, Christian, Krumbholz, Manuela, Lecanda, Fernando, Lemma, Silvia, Longo, Dario L., Madrigal-Esquivel, Claudia, Morales-Molina, Alvaro, Musa, Julian, Ohmura, Shunya, Ory, Benjamin, Pereira-Silva, Miguel, Perut, Francesca, Rodriguez, Rene, Seeling, Carolin, Al Shaaili, Nada, Shaabani, Shabnam, Shiavone, Kristina, Sinha, Snehadri, Tomazou, Eleni M., Trautmann, Marcel, Vela, Maria, Versleijen-Jonkers, Yvonne M. H., Visgauss, Julia, Zalacain, Marta, Schober, Sebastian J., Lissat, Andrej, English, William R., Baldini, Nicola, Heymann, Dominique, Department of Oral and Maxillofacial Diseases, University of Helsinki, and HUS Helsinki and Uusimaa Hospital District

Subjects
EARLY METABOLIC-RESPONSE, Cancer Research, GASTROINTESTINAL STROMAL TUMORS, 3122 Cancers, bone sarcoma, CONDITIONALLY REPLICATIVE ADENOVIRUS, INFILTRATING T-CELLS, PATIENT-DERIVED XENOGRAFTS, targeted therapy, CIRCULATING TUMOR-CELLS, molecular diagnostics, SOFT-TISSUE SARCOMA, soft tissue sarcoma, CANCER STEM-CELLS, ENDOTHELIAL GROWTH-FACTOR, LIMB-SALVAGE TREATMENT, molecular medicine
Abstract

Sarcomas are heterogeneous and clinically challenging soft tissue and bone cancers. Although constituting only 1% of all human malignancies, sarcomas represent the second most common type of solid tumors in children and adolescents and comprise an important group of secondary malignancies. More than 100 histological subtypes have been characterized to date, and many more are being discovered due to molecular profiling. Owing to their mostly aggressive biological behavior, relative rarity, and occurrence at virtually every anatomical site, many sarcoma subtypes are in particular difficult-to-treat categories. Current multimodal treatment concepts combine surgery, polychemotherapy (with/without local hyperthermia), irradiation, immunotherapy, and/or targeted therapeutics. Recent scientific advancements have enabled a more precise molecular characterization of sarcoma subtypes and revealed novel therapeutic targets and prognostic/predictive biomarkers. This review aims at providing a comprehensive overview of the latest advances in the molecular biology of sarcomas and their effects on clinical oncology; it is meant for a broad readership ranging from novices to experts in the field of sarcoma.

Published
2020

15. Sarcoma treatment in the era of molecular medicine

Author

Grünewald, Thomas GP, primary, Alonso, Marta, additional, Avnet, Sofia, additional, Banito, Ana, additional, Burdach, Stefan, additional, Cidre‐Aranaz, Florencia, additional, Di Pompo, Gemma, additional, Distel, Martin, additional, Dorado‐Garcia, Heathcliff, additional, Garcia‐Castro, Javier, additional, González‐González, Laura, additional, Grigoriadis, Agamemnon E, additional, Kasan, Merve, additional, Koelsche, Christian, additional, Krumbholz, Manuela, additional, Lecanda, Fernando, additional, Lemma, Silvia, additional, Longo, Dario L, additional, Madrigal‐Esquivel, Claudia, additional, Morales‐Molina, Álvaro, additional, Musa, Julian, additional, Ohmura, Shunya, additional, Ory, Benjamin, additional, Pereira‐Silva, Miguel, additional, Perut, Francesca, additional, Rodriguez, Rene, additional, Seeling, Carolin, additional, Al Shaaili, Nada, additional, Shaabani, Shabnam, additional, Shiavone, Kristina, additional, Sinha, Snehadri, additional, Tomazou, Eleni M, additional, Trautmann, Marcel, additional, Vela, Maria, additional, Versleijen‐Jonkers, Yvonne MH, additional, Visgauss, Julia, additional, Zalacain, Marta, additional, Schober, Sebastian J, additional, Lissat, Andrej, additional, English, William R, additional, Baldini, Nicola, additional, and Heymann, Dominique, additional

Published
2020
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18. 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*, 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(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

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

Published
2018
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23. Altered pH gradient at the plasma membrane of osteosarcoma cells is a key mechanism of drug resistance

Author

Avnet, Sofia, primary, Lemma, Silvia, additional, Cortini, Margherita, additional, Pellegrini, Paola, additional, Perut, Francesca, additional, Zini, Nicoletta, additional, Kusuzaki, Katsuyuki, additional, Chano, Tokuhiro, additional, Grisendi, Giulia, additional, Dominici, Massimo, additional, De Milito, Angelo, additional, and Baldini, Nicola, additional

Published
2016
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24. Human bone marrow- and adipose-mesenchymal stem cells secrete exosomes enriched in distinctive miRNA and tRNA species

Author

Baglio, Serena Rubina, primary, Rooijers, Koos, additional, Koppers-Lalic, Danijela, additional, Verweij, Frederik J., additional, Pérez Lanzón, M, additional, Zini, Nicoletta, additional, Naaijkens, Benno, additional, Perut, Francesca, additional, Niessen, Hans W. M., additional, Baldini, Nicola, additional, and Pegtel, D. Michiel, additional

Published
2015
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28. Osteoblasts from a mandibuloacral dysplasia patient induce human blood precursors to differentiate into active osteoclasts

Author

Avnet, Sofia, primary, Pallotta, Rosanna, additional, Perut, Francesca, additional, Baldini, Nicola, additional, Pittis, Maria Gabriela, additional, Saponari, Anita, additional, Lucarelli, Enrico, additional, Dozza, Barbara, additional, Greggi, Tiziana, additional, Maraldi, Nadir M., additional, Capanni, Cristina, additional, Mattioli, Elisabetta, additional, Columbaro, Marta, additional, and Lattanzi, Giovanna, additional

Published
2011
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30. In vitro evaluation of freeze-dried bone allografts combined with platelet rich plasma and human bone marrow stromal cells for tissue engineering

Author

Cenni, Elisabetta, primary, Perut, Francesca, additional, Ciapetti, Gabriela, additional, Savarino, Lucia, additional, Dallari, Dante, additional, Cenacchi, Annarita, additional, Stagni, Cesare, additional, Giunti, Armando, additional, Fornasari, Pier Maria, additional, and Baldini, Nicola, additional

Published
2008
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31. In vitro models for the evaluation of angiogenic potential in bone engineering.

Author

Cenni, Elisabetta, Perut, Francesca, and Baldini, Nicola

Subjects
HOMEOSTASIS, BONE surgery, TISSUE engineering, NEOVASCULARIZATION, CELL adhesion, CELL proliferation, RECOMBINANT proteins, VASCULAR endothelial growth factors
Abstract

Blood vessels have a fundamental role both in skeletal homeostasis and in bone repair. Angiogenesis is also important for a successful bone engineering. Therefore, scaffolds should be tested for their ability to favour endothelial cell adhesion, proliferation and functions. The type of endothelial cell to use for in vitro assays should be carefully considered, because the properties of these cells may depend on their source. Morphological and functional relationships between endothelial cells and osteoblasts are evaluated with co-cultures, but this model should still be standardized, particularly for distinguishing the two cell types. Platelet-rich plasma and recombinant growth factors may be useful for stimulating angiogenesis. [ABSTRACT FROM AUTHOR]

Published
2011
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32. FT-IR Spectral Signature of Sensitive and Multidrug-Resistant Osteosarcoma Cell-Derived Extracellular Nanovesicles

Author

Francesca Perut, Gabriela Graziani, Laura Roncuzzi, Nicoletta Zini, Sofia Avnet, Nicola Baldini, Perut, Francesca, Graziani, Gabriela, Roncuzzi, Laura, Zini, Nicoletta, Avnet, Sofia, and Baldini, Nicola

Subjects
Osteosarcoma, Adolescent, Extracellular Vesicle, FT-IR/ATR spectroscopy, extracellular nanovesicles, osteosarcoma, multidrug resistance, non-invasive diagnostics, Bone Neoplasms, extracellular nanovesicle, General Medicine, Bone Neoplasm, Drug Resistance, Multiple, Extracellular Vesicles, Spectroscopy, Fourier Transform Infrared, Humans, Child, non-invasive diagnostic, Human
Abstract

Osteosarcoma (OS) is the most common primary bone cancer in children and adolescents. Despite aggressive treatment regimens, the outcome is unsatisfactory, and multidrug resistance (MDR) is a pivotal process in OS treatment failure. OS-derived extracellular vesicles (EVs) promote drug resistance to chemotherapy and target therapy through different mechanisms. The aim of this study was to identify subpopulations of osteosarcoma-EVs by Fourier transform infrared spectroscopy (FT-IR) to define a specific spectral signature for sensitive and multidrug-resistant OS-derived EVs. EVs were isolated from sensitive and MDR OS cells as well as from mesenchymal stem cells by differential centrifugation and ultracentrifugation. EVs size, morphology and protein expression were characterized. FT-IR/ATR of EVs spectra were acquired in the region of 400–4000 cm−1 (resolution 4 cm−1, 128 scans). The FT-IR spectra obtained were consistently different in the EVs compared to cells from which they originate. A specific spectral signature, characterized by a shift and a new band (1601 cm−1), permitted to clearly distinguish EVs isolated by sensitive and multidrug-resistant OS cells. Our data suggest that FT-IR spectroscopy allows to characterize and define a specific spectral signature for sensitive and MDR OS-derived EVs.

Published
2022
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33. Altered pH gradient at the plasma membrane of osteosarcoma cells is a key mechanism of drug resistance

Author

Tokuhiro Chano, Silvia Lemma, Sofia Avnet, Massimo Dominici, Nicoletta Zini, Margherita Cortini, Nicola Baldini, Giulia Grisendi, Francesca Perut, Katsuyuki Kusuzaki, Angelo De Milito, Paola Pellegrini, Avnet, Sofia, Lemma, Silvia, Cortini, Margherita, Pellegrini, Paola, Perut, Francesca, Zini, Nicoletta, Kusuzaki, Katsuyuki, Chano, Tokuhiro, Grisendi, Giulia, Dominici, Massimo, De Milito, Angelo, and Baldini, Nicola

Subjects
Male, 0301 basic medicine, Pathology, medicine.medical_specialty, Vincristine, medicine.medical_treatment, Antineoplastic Agents, Apoptosis, Bone Neoplasms, Mice, SCID, Drug resistance, Pharmacology, doxorubicin, Mice, 03 medical and health sciences, 0302 clinical medicine, Mice, Inbred NOD, osteosarcoma, Tumor Cells, Cultured, Tumor Microenvironment, medicine, Animals, Humans, Doxorubicin, ATP Binding Cassette Transporter, Subfamily B, Member 1, Cell Proliferation, Cisplatin, Chemotherapy, drug resistance, Osteosarcoma, Plasma membrane pH gradient, Tumor microenvironment, Oncology, business.industry, Cell Membrane, Hydrogen-Ion Concentration, medicine.disease, Xenograft Model Antitumor Assays, Drug Resistance, Multiple, 030104 developmental biology, Drug Resistance, Neoplasm, 030220 oncology & carcinogenesis, Toxicity, Muramidase, Methotrexate, plasma membrane pH gradient, business, Research Paper, medicine.drug
Abstract

// Sofia Avnet 1 , Silvia Lemma 1 , Margherita Cortini 1 , Paola Pellegrini 2 , Francesca Perut 1 , Nicoletta Zini 3, 4 , Katsuyuki Kusuzaki 5 , Tokuhiro Chano 6 , Giulia Grisendi 7 , Massimo Dominici 7 , Angelo De Milito 2 , Nicola Baldini 1, 8 1 Orthopaedic Pathophysiology and Regenerative Medicine Unit, Istituto Ortopedico Rizzoli, Bologna, Italy 2 Department of Oncology-Pathology, Cancer Center Karolinska, Karolinska Institute, Stockholm, Sweden 3 CNR - National Research Council of Italy, Institute of Molecular Genetics, Bologna, Italy 4 Laboratory of Musculoskeletal Cell Biology, Istituto Ortopedico Rizzoli, Bologna, Italy 5 Musculoskeletal Oncology Unit, Takai Hospital, Nara, Japan 6 Department of Clinical Laboratory Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan 7 Department of Medical and Surgical Sciences for Children and Adults, University-hospital of Modena e Reggio Emilia, Modena, Italy 8 Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy Correspondence to: Nicola Baldini, email: nicola.baldini@ior.it Keywords: osteosarcoma, doxorubicin, drug resistance, plasma membrane pH gradient, tumor microenvironment Received: April 19, 2016 Accepted: August 10, 2016 Published: August 22, 2016 ABSTRACT Current therapy of osteosarcoma (OS), the most common primary bone malignancy, is based on a combination of surgery and chemotherapy. Multidrug resistance mediated by P-glycoprotein (P-gp) overexpression has been previously associated with treatment failure and progression of OS, although other mechanisms may also play a role. We considered the typical acidic extracellular pH (pHe) of sarcomas, and found that doxorubicin (DXR) cytotoxicity is reduced in P-gp negative OS cells cultured at pHe 6.5 compared to standard 7.4. Short-time (24–48 hours) exposure to low pHe significantly increased the number and acidity of lysosomes, and the combination of DXR with omeprazole, a proton pump inhibitor targeting lysosomal acidity, significantly enhanced DXR cytotoxicity. In OS xenografts, the combination treatment of DXR and omeprazole significantly reduced tumor volume and body weight loss. The impaired toxicity of DXR at low pHe was not associated with increased autophagy or lysosomal acidification, but rather, as shown by SNARF staining, with a reversal of the pH gradient at the plasma membrane (ΔpH cm ), eventually leading to a reduced DXR intracellular accumulation. Finally, the reversal of ΔpH cm in OS cells promoted resistance not only to DXR, but also to cisplatin and methotrexate, and, to a lesser extent, to vincristine. Altogether, our findings show that, in OS cells, short-term acidosis induces resistance to different chemotherapeutic drugs by a reversal of ΔpH cm , suggesting that buffer therapies or regimens including proton pump inhibitors in combination to low concentrations of conventional anticancer agents may offer novel solutions to overcome drug resistance.

Published
2016

34. Multimodal transfer of MDR by exosomes in human osteosarcoma

Author

Francesca Perut, Elena Torreggiani, Laura Roncuzzi, Nicola Baldini, Nicoletta Zini, Torreggiani, Elena, Roncuzzi, Laura, Perut, Francesca, Zini, Nicoletta, and Baldini, Nicola

Subjects
0301 basic medicine, Cancer Research, ATP Binding Cassette Transporter, Subfamily B, Cell, Apoptosis, exosomes, Cell Communication, Exosome, NO, 03 medical and health sciences, 0302 clinical medicine, Cell Line, Tumor, medicine, Humans, P-glycoprotein, Drug-resistance, Osteosarcoma, biology, Oncogene, P-Glycoprotein, Apoptosi, medicine.disease, Microvesicles, Drug Resistance, Multiple, Gene Expression Regulation, Neoplastic, 030104 developmental biology, medicine.anatomical_structure, exosomes, drug-resistance, P-glycoprotein, doxorubicin, osteosarcoma, Oncology, Cell culture, Doxorubicin, Drug Resistance, Neoplasm, 030220 oncology & carcinogenesis, biology.protein, Cancer research, Human
Abstract

Exosomes are extracellular vesicles released by both normal and tumour cells which are involved in a new intercellular communication pathway by delivering cargo (e.g., proteins, microRNAs, mRNAs) to recipient cells. Tumour-derived exosomes have been shown to play critical roles in different stages of tumour growth and progression. In this study, we investigated the potential role of exosomes to transfer the multidrug resistance (MDR) phenotype in human osteosarcoma cells. Exosomes were isolated by differential centrifugation of culture media from multidrug resistant human osteosarcoma MG-63DXR30 (Exo/DXR) and MG-63 parental cells (Exo/S). Exosome purity was examined by transmission electron microscopy and confirmed by immunoblot analysis for the expression of specific exosomal markers. Our data showed that exosomes derived from doxorubicin-resistant osteosarcoma cells could be taken up into secondary cells and induce a doxorubicin-resistant phenotype. The incubation of osteosarcoma cells with Exo/DXR decreased the sensitivity of parental cells to doxorubicin, while exposure with Exo/S was ineffective. In addition, we demonstrated that Exo/DXR expressed higher levels of MDR-1 mRNA and P-glycoprotein compared to Exo/S (p=0.03). Interestingly, both MDR-1 mRNA and P-gp increased in MG-63 cells after incubation with Exo/DXR, suggesting this as the main mechanism of exosome-mediated transfer of drug resistance. Our findings suggest that multidrug resistant osteosarcoma cells are able to spread their ability to resist the effects of doxorubicin treatment on sensitive cells by transferring exosomes carrying MDR-1 mRNA and its product P-glycoprotein.

Published
2016

35. Human bone marrow- and adipose-mesenchymal stem cells secrete exosomes enriched in distinctive miRNA and tRNA species

Author

Nicola Baldini, Danijela Koppers-Lalic, M Pérez Lanzón, Nicoletta Zini, Frederik J. Verweij, Koos Rooijers, Serena Rubina Baglìo, Francesca Perut, B.A. Naaijkens, D. Michiel Pegtel, Hans W.M. Niessen, Pathology, Cardio-thoracic surgery, CCA - Oncogenesis, ICaR - Ischemia and repair, Baglio, Serena Rubina, Rooijers, Koo, Koppers-Lalic, Danijela, Verweij, Frederik J, Pérez Lanzón, M, Zini, Nicoletta, Naaijkens, Benno, Perut, Francesca, Niessen, Hans W M, Baldini, Nicola, and Pegtel, D Michiel

Subjects
Homeobox protein NANOG, Small RNA, Cellular differentiation, 3' Untranslated Region, Medicine (miscellaneous), Bone Marrow Cells, Biology, Exosomes, Biochemistry, Genetics and Molecular Biology (miscellaneous), RNA, Transfer, microRNA, Humans, Small nucleolar RNA, 3' Untranslated Regions, Cells, Cultured, Base Sequence, Mesenchymal Stromal Cell, Sequence Analysis, RNA, Research, Mesenchymal stem cell, RNA, Mesenchymal Stem Cells, Cell Differentiation, MicroRNA, Cell Biology, Microvesicles, Cell biology, Exosome, MicroRNAs, Microscopy, Electron, Adipose Tissue, Molecular Medicine, Bone Marrow Cell, Transcriptome, Human
Abstract

Introduction Administration of mesenchymal stem cells (MSCs) represents a promising treatment option for patients suffering from immunological and degenerative disorders. Accumulating evidence indicates that the healing effects of MSCs are mainly related to unique paracrine properties, opening opportunities for secretome-based therapies. Apart from soluble factors, MSCs release functional small RNAs via extracellular vesicles (EVs) that seem to convey essential features of MSCs. Here we set out to characterize the full small RNAome of MSC-produced exosomes. Methods We set up a protocol for isolating exosomes released by early passage adipose- (ASC) and bone marrow-MSCs (BMSC) and characterized them via electron microscopy, protein analysis and small RNA-sequencing. We developed a bioinformatics pipeline to define the exosome-enclosed RNA species and performed the first complete small RNA characterization of BMSCs and ASCs and their corresponding exosomes in biological replicates. Results Our analysis revealed that primary ASCs and BMSCs have highly similar small RNA expression profiles dominated by miRNAs and snoRNAs (together 64-71 %), of which 150–200 miRNAs are present at physiological levels. In contrast, the miRNA pool in MSC exosomes is only 2-5 % of the total small RNAome and is dominated by a minor subset of miRNAs. Nevertheless, the miRNAs in exosomes do not merely reflect the cellular content and a defined set of miRNAs are overrepresented in exosomes compared to the cell of origin. Moreover, multiple highly expressed miRNAs are precluded from exosomal sorting, consistent with the notion that these miRNAs are involved in functional repression of RNA targets. While ASC and BMSC exosomes are similar in RNA class distribution and composition, we observed striking differences in the sorting of evolutionary conserved tRNA species that seems associated with the differentiation status of MSCs, as defined by Sox2, POU5F1A/B and Nanog expression. Conclusions We demonstrate that primary MSCs release small RNAs via exosomes, which are increasingly implicated in intercellular communications. tRNAs species, and in particular tRNA halves, are preferentially released and their specific sorting into exosomes is related to MSC tissue origin and stemness. These findings may help to understand how MSCs impact neighboring or distant cells with possible consequences for their therapeutic usage. Electronic supplementary material The online version of this article (doi:10.1186/s13287-015-0116-z) contains supplementary material, which is available to authorized users.

Published
2015

36. Inhibition of angiogenesis via FGF-2 blockage in primitive and bone metastatic renal cell carcinoma.

Author

Cenni E, Perut F, Granchi D, Avnet S, Amato I, Brandi ML, Giunti A, and Baldini N

Subjects
Antibodies, Monoclonal immunology, Antibodies, Monoclonal pharmacology, Bone Neoplasms metabolism, Bone Neoplasms therapy, Carcinoma, Renal Cell metabolism, Carcinoma, Renal Cell secondary, Carcinoma, Renal Cell therapy, Cell Growth Processes drug effects, Cell Growth Processes genetics, Cell Growth Processes immunology, Cell Line, Tumor, Endothelial Cells cytology, Endothelial Cells drug effects, Endothelial Cells metabolism, Fibroblast Growth Factor 2 biosynthesis, Fibroblast Growth Factor 2 genetics, Fibroblast Growth Factor 2 immunology, Humans, Kidney Neoplasms metabolism, Kidney Neoplasms therapy, Neovascularization, Pathologic metabolism, Neovascularization, Pathologic therapy, Oligonucleotides, Antisense genetics, Oligonucleotides, Antisense pharmacology, RNA, Messenger biosynthesis, RNA, Messenger genetics, Bone Neoplasms blood supply, Bone Neoplasms secondary, Carcinoma, Renal Cell blood supply, Fibroblast Growth Factor 2 antagonists & inhibitors, Kidney Neoplasms blood supply
Abstract

Background: Fibroblast growth factor-2 (FGF-2) has a role in the angiogenesis induced by renal carcinoma., Materials and Methods: Blockage of FGF-2 by an antisense oligonucleotide (ASO) or by a mouse neutralizing anti-human FGF-2 monoclonal antibody (anti-FGF-2-mAb) was evaluated on a cell line isolated from a renal carcinoma bone metastasis (CRBM-1990), on Caki-1 and ACHN cells. Cocultures of endothelial cells and ASO- or mAb-treated carcinoma lines were investigated., Results: Anti-FGF-2-mAb treatment induced a 33% reduction of FGF-2 released by ACHN, a 31% reduction of FGF-2 released by Caki-1, and a 70% reduction of FGF-2 released by CRBM-1990. ASO treatment did not inhibit endothelial cell proliferation. In contrast, anti-FGF-2-mAb significantly decreased endothelial cells proliferation induced by ACHN and CRBM-1990. The inhibition of endothelial cell growth was reverted by recombinant FGF-2., Conclusion: Modulation of FGF-2 production by renal cell carcinoma with a blocking mAb produced a significant inhibition of endothelial cell growth.

Published
2007

37. Primitive and bone metastatic renal carcinoma cells promote osteoclastogenesis through endothelial cells.

Author

Cenni E, Perut F, Granchi D, Amato I, Avnet S, Brandi ML, Giunti A, and Baldini N

Subjects
Acid Phosphatase metabolism, Animals, Bone Neoplasms blood, Bone Neoplasms blood supply, Bone Neoplasms enzymology, Carcinoma, Renal Cell blood, Carcinoma, Renal Cell blood supply, Carcinoma, Renal Cell enzymology, Carcinoma, Renal Cell secondary, Cattle, Cell Line, Tumor, Culture Media, Conditioned, Endothelial Cells enzymology, Gene Expression, Humans, Interleukin-6 biosynthesis, Interleukin-6 genetics, Isoenzymes metabolism, Kidney Neoplasms blood, Kidney Neoplasms blood supply, Kidney Neoplasms enzymology, Leukocytes, Mononuclear pathology, Neovascularization, Pathologic pathology, Osteoclasts enzymology, Osteoclasts pathology, Tartrate-Resistant Acid Phosphatase, Bone Neoplasms secondary, Carcinoma, Renal Cell pathology, Endothelial Cells pathology, Kidney Neoplasms pathology
Abstract

Background: The contribution of angiogenesis to renal carcinoma bone metastases is virtually unknown., Materials and Methods: The effect of a cell line from a renal carcinoma bone metastasis (CRBM) was compared in vitro with the primitive renal adenocarcinoma line ACHN, by evaluating the influence on the ability of bone endothelial cells to activate osteoclasts., Results: The ACHN-conditioned medium produced a significant expression of macrophage-colony-stimulating factor mRNA. The conditioned medium from ACHN, CRBM, or from endothelial cells previously stimulated with the neoplastic cell-conditioned media, had no direct effect on osteoclast differentiation from blood precursors (PBMC), such as CRBM and ACHN co-cultured with PBMC. However, PBMC co-cultured with endothelial cells previously stimulated with the CRBM-conditioned medium showed significantly higher levels of tartrate-resistant acid phosphatase., Conclusion: It is possible that the bone metastatic line CRBM releases factors that induce endothelial cells to favor osteoclast differentiation.

Published
2006

38. Inhibition of angiogenic activity of renal carcinoma by an antisense oligonucleotide targeting fibroblast growth factor-2.

Author

Cenni E, Perut F, Zuntini M, Granchi D, Amato I, Avnet S, Brandi ML, Giunti A, and Baldini N

Subjects
Blotting, Western, Carcinoma, Renal Cell genetics, Carcinoma, Renal Cell metabolism, Cell Growth Processes genetics, Cell Line, Tumor, Chemotaxis genetics, Endothelial Cells cytology, Endothelial Cells physiology, Fibroblast Growth Factor 2 biosynthesis, Fibroblast Growth Factor 2 genetics, Humans, Kidney Neoplasms genetics, Kidney Neoplasms metabolism, Neovascularization, Pathologic genetics, Oligonucleotides, Antisense genetics, RNA, Messenger biosynthesis, RNA, Messenger genetics, Reverse Transcriptase Polymerase Chain Reaction, Transfection, Carcinoma, Renal Cell blood supply, Carcinoma, Renal Cell therapy, Fibroblast Growth Factor 2 antagonists & inhibitors, Kidney Neoplasms blood supply, Kidney Neoplasms therapy, Neovascularization, Pathologic prevention & control
Abstract

Background: Fibroblast growth factor-2 (FGF-2) induces angiogenesis, critical for the growth and metastatic spread of tumors., Materials and Methods: The effect of blocking FGF-2 synthesis by an antisense phosphorothioate oligodeoxynucleotide (PS-ODN2) was evaluated on the angiogenic activity of Caki-1 and of a cell line isolated from a renal carcinoma bone metastasis (CRBM-1990). After the transfection with PS-ODN2, FGF-2 mRNA, protein expression and angiogenic activity were evaluated., Results: In Caki-1, a not significant decrease in the released FGF-2 was observed after 72 hours. In CRBM-1990, a not significant decrease in intracellular FGF-2 protein was observed after 72 hours. Endothelial cell migration induced by the conditioned media from Caki-1 treated with PS-ODN2 for 72 hours was significantly reduced., Conclusion: PS-ODN2 treatment of the established line Caki-1 induced minimal variations in FGF-2 expression, but inhibited endothelial cell migration. In CRBM-1990 cells, PS-ODN2 determined a decrease in intracellular protein without reducing the ability to induce endothelial cell migration and proliferation.

Published
2005

39. Isolation and characterization of a new cell line from a renal carcinoma bone metastasis.

Author

Avnet S, Cenni E, Granchi D, Perut F, Amato I, Battistelli L, Brandi ML, Giunti A, and Baldini N

Subjects
Aged, Angiogenic Proteins biosynthesis, Angiogenic Proteins genetics, Animals, Bone Neoplasms metabolism, Carcinoma, Renal Cell metabolism, Carrier Proteins biosynthesis, Carrier Proteins genetics, Cattle, Chemotaxis, Endothelium, Vascular cytology, Endothelium, Vascular drug effects, Humans, Interleukin-6 biosynthesis, Interleukin-6 genetics, Kidney Neoplasms metabolism, Male, Membrane Glycoproteins biosynthesis, Membrane Glycoproteins genetics, Protein Biosynthesis, Proteins genetics, Proto-Oncogene Proteins c-met, RANK Ligand, RNA, Messenger biosynthesis, RNA, Messenger genetics, Receptor Activator of Nuclear Factor-kappa B, Reverse Transcriptase Polymerase Chain Reaction, Transforming Growth Factor beta biosynthesis, Transforming Growth Factor beta genetics, Bone Neoplasms secondary, Carcinoma, Renal Cell secondary, Cell Line, Tumor, Kidney Neoplasms pathology, Proto-Oncogene Proteins, Receptors, Growth Factor
Abstract

Background: The use of cell lines isolated from metastases should enable the assessment of peculiar aspects of bone resorbing cytokine expression, as well as angiogenetic activity of renal carcinoma bone metastases., Materials and Methods: A cell line (CRBM-1990) was isolated from a renal cell carcinoma bone metastasis and compared with the ACHN and Caki-1 established lines. The expression of osteolytic cytokine and angiogenetic growth factors mRNAs, as well as the effect on migration and proliferation of a bovine bone cell line (BBE) were determined., Results: There were no significant differences between the three lines in IL-6, TGF-beta, VEGF-A, VEGF-B, VEGF-C and FGF-2 mRNAs expression. VEGF-D, PIGF, or RANK-L-specific mRNA were not expressed. CRBM-1990-, Caki-1- and ACHN-conditioned media significantly stimulated the migration and proliferation of BBE., Conclusion: CRBM-1990 expressed IL-6-specific mRNA, but not RANK-L, expressed angiogenetic growth factors and induced migration and proliferation of bone endothelial cells at a non-significantly different level when compared with Caki-1 and ACHN.

Published
2004

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