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Your search keyword '"Clayton, Aled"' showing total 19 results
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19 results on '"Clayton, Aled"'

1. Extracellular vesicles derived from umbilical cord mesenchymal stromal cells show enhanced anti-inflammatory properties via upregulation of miRNAs after pro-inflammatory priming.

Author

Hyland M, Mennan C, Davies R, Wilson E, Tonge DP, Clayton A, and Kehoe O

Subjects
Humans, Leukocytes, Mononuclear metabolism, Up-Regulation genetics, Cytokines metabolism, Anti-Inflammatory Agents pharmacology, Umbilical Cord metabolism, MicroRNAs genetics, MicroRNAs metabolism, Extracellular Vesicles metabolism, Mesenchymal Stem Cells metabolism
Abstract

Autoimmune conditions, such as rheumatoid arthritis, are characterised by a loss of immune tolerance, whereby the immune cells attack self-antigens causing pain and inflammation. These conditions can be brought into remission using pharmaceutical treatments, but often have adverse side effects and some patients do not respond favourably to them. Human umbilical cord mesenchymal stromal cells (UCMSCs) present a promising alternative therapeutic due to their innate anti-inflammatory properties which can be strengthened using pro-inflammatory conditions. Their therapeutic mechanism of action has been attributed to paracrine signalling, by which nanosized acellular particles called 'extracellular vesicles' (EVs) are one of the essential components. Therefore, this research analysed the anti-inflammatory properties of UCMSC-EVs 'primed' with pro-inflammatory cytokines and at baseline with no inflammatory cytokines (control). Both control and primed EVs were co-cultured with un-pooled peripheral blood mononuclear cells (PBMCs; n = 6) from healthy donors. Neither control nor primed EVs exerted a pro-inflammatory effect on PBMCs. Instead, the primed EVs showed the immunosuppressive potential by increasing the expression of the anti-inflammatory protein FoxP3 in PBMCs. This may be attributed to the upregulated miRNAs identified in primed EVs in comparison to control EVs (miR-139-5p, miR-140-5p, miR-214-5p). These findings aid in understanding how UCMSC-EVs mediate immunosuppression and support their potential use in treating autoimmune conditions., (© 2023. The Author(s).)

Published
2023
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2. Dual-Wave Acoustofluidic Centrifuge for Ultrafast Concentration of Nanoparticles and Extracellular Vesicles.

Author

Dumčius P, Mikhaylov R, Zhang X, Bareford M, Stringer M, Errington R, Sun C, Gonzalez E, Krukovski T, Falcon-Perez JM, Liang D, Fu YQ, Clayton A, and Yang X

Subjects
Male, Humans, Cryoelectron Microscopy, Cell Line, Extracellular Vesicles metabolism, Prostatic Neoplasms, Nanospheres
Abstract

Extracellular vesicles (EVs) are secreted nanostructures that play various roles in critical cancer processes. They operate as an intercellular communication system, transferring complex sets of biomolecules from cell to cell. The concentration of EVs is difficult to decipher, and there is an unmet technological need for improved (faster, simpler, and gentler) approaches to isolate EVs from complex matrices. Herein, an acoustofluidic concentration of extracellular vesicles (ACEV) is presented, based on a thin-film printed circuit board with interdigital electrodes mounted on a piezoelectric substrate. An angle of 120° is identified between the electrodes and the reference flat of the piezoelectric substrate for simultaneous generation of Rayleigh and shear horizontal waves. The dual waves create a complex acoustic field in a droplet, resulting in effective concentration of nanoparticles and EVs. The ACEV is able to concentrate 20 nm nanospheres within 105 s and four EV dilutions derived from the human prostate cancer (Du145) cell line in approximately 30 s. Cryo-electron microscopy confirmed the preservation of EV integrity. The ACEV device holds great potential to revolutionize investigations of EVs. Its faster, simpler, and gentler approach to EV isolation and concentration can save time and effort in phenotypic and functional studies of EVs., (© 2023 The Authors. Small published by Wiley-VCH GmbH.)

Published
2023
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3. Oral Progenitor Cell Line-Derived Small Extracellular Vesicles as a Treatment for Preferential Wound Healing Outcome.

Author

Knight R, Board-Davies E, Brown H, Clayton A, Davis T, Karatas B, Burston J, Tabi Z, Falcon-Perez JM, Paisey S, and Stephens P

Subjects
Cell Proliferation, Cicatrix metabolism, Humans, Stem Cells, Extracellular Vesicles metabolism, Mesenchymal Stem Cells
Abstract

Scar formation during wound repair can be devastating for affected individuals. Our group previously documented the therapeutic potential of novel progenitor cell populations from the non-scarring buccal mucosa. These Oral Mucosa Lamina Propria-Progenitor Cells (OMLP-PCs) are multipotent, immunosuppressive, and antibacterial. Small extracellular vesicles (sEVs) may play important roles in stem cell-mediated repair in varied settings; hence, we investigated sEVs from this source for wound repair. We created an hTERT immortalized OMLP-PC line (OMLP-PCL) and confirmed retention of morphology, lineage plasticity, surface markers, and functional properties. sEVs isolated from OMLP-PCL were analyzed by nanoparticle tracking analysis, Cryo-EM and flow cytometry. Compared to bone marrow-derived mesenchymal stromal cells (BM-MSC) sEVs, OMLP-PCL sEVs were more potent at driving wound healing functions, including cell proliferation and wound repopulation and downregulated myofibroblast formation. A reduced scarring potential was further demonstrated in a preclinical in vivo model. Manipulation of OMLP-PCL sEVs may provide novel options for non-scarring wound healing in clinical settings., (© The Author(s) 2022. Published by Oxford University Press.)

Published
2022
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4. Challenges and directions in studying cell-cell communication by extracellular vesicles.

Author

van Niel G, Carter DRF, Clayton A, Lambert DW, Raposo G, and Vader P

Subjects
Biological Transport, Biomarkers metabolism, Cell Communication, Drug Delivery Systems, Extracellular Vesicles metabolism
Abstract

Extracellular vesicles (EVs) are increasingly recognized as important mediators of intercellular communication. They have important roles in numerous physiological and pathological processes, and show considerable promise as novel biomarkers of disease, as therapeutic agents and as drug delivery vehicles. Intriguingly, however, understanding of the cellular and molecular mechanisms that govern the many observed functions of EVs remains far from comprehensive, at least partly due to technical challenges in working with these small messengers. Here, we highlight areas of consensus as well as contentious issues in our understanding of the intracellular and intercellular journey of EVs: from biogenesis, release and dynamics in the extracellular space, to interaction with and uptake by recipient cells. We define knowledge gaps, identify key questions and challenges, and make recommendations on how to address these., (© 2022. Springer Nature Limited.)

Published
2022
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5. The role of bacterial extracellular vesicles in chronic wound infections: Current knowledge and future challenges.

Author

Brown HL, Clayton A, and Stephens P

Subjects
Biofilms, Humans, Pseudomonas aeruginosa, Reproducibility of Results, Wound Healing, Extracellular Vesicles, Pseudomonas Infections, Wound Infection
Abstract

Chronic wounds are a significant global problem with an increasing economic and patient welfare impact. How wounds move from an acute to chronic, non-healing, state is not well understood although it is likely that it is driven by a poorly regulated local inflammatory state. Opportunistic pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa are well known to stimulate a pro-inflammatory response and so their presence may further drive chronicity. Studies have demonstrated that host cell extracellular vesicles (hEVs), in particular exosomes, have multiple roles in both increasing and decreasing chronicity within wounds; however, the role of bacterial extracellular vesicles (bEVs) is still poorly understood. The aim of this review is to evaluate bEV biogenesis and function within chronic wound relevant bacterial species to determine what, if any, role bEVs may have in driving wound chronicity. We determine that bEVs drive chronicity by both increasing persistence of key pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa and stimulating a pro-inflammatory response by the host. Data also suggest that both bEVs and hEVs show therapeutic promise, providing vaccine candidates, decoy targets for bacterial toxins or modulating the bacterial species within chronic wound biofilms. Caution should, however, be used when interpreting findings to date as the bEV field is still in its infancy and as such lacks consistency in bEV isolation and characterization. It is of primary importance that this is addressed, allowing meaningful conclusions to be drawn and increasing reproducibility within the field., (© 2021 The Authors. Wound Repair and Regeneration published by Wiley Periodicals LLC on behalf of The Wound Healing Society.)

Published
2021
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6. Stroma-derived extracellular vesicle mRNA signatures inform histological nature of prostate cancer.

Author

Shephard AP, Giles P, Mbengue M, Alraies A, Spary LK, Kynaston H, Gurney MJ, Falcón-Pérez JM, Royo F, Tabi Z, Parthimos D, Errington RJ, Clayton A, and Webber JP

Subjects
Humans, Male, Biomarkers, Tumor metabolism, Extracellular Vesicles metabolism, Prostatic Neoplasms genetics, RNA, Messenger genetics
Abstract

Histological assessment of prostate cancer is the key diagnostic test and can predict disease outcome. This is however an invasive procedure that carries associated risks, hence non-invasive assays to support the diagnostic pathway are much needed. A key feature of disease progression, and subsequent poor prognosis, is the presence of an altered stroma. Here we explored the utility of prostate stromal cell-derived vesicles as indicators of an altered tumour environment. We compared vesicles from six donor-matched pairs of adjacent-normal versus disease-associated primary stromal cultures. We identified 19 differentially expressed transcripts that discriminate disease from normal stromal extracellular vesicles (EVs). EVs isolated from patient serum were investigated for these putative disease-discriminating mRNA. A set of transcripts including Caveolin-1 (CAV1), TMP2, THBS1, and CTGF were found to be successful in discriminating clinically insignificant (Gleason = 6) disease from clinically significant (Gleason > 8) prostate cancer. Furthermore, correlation between transcript expression and progression-free survival suggests that levels of these mRNA may predict disease outcome. Informed by a machine learning approach, combining measures of the five most informative EV-associated mRNAs with PSA was shown to significantly improve assay sensitivity and specificity. An in-silico model was produced, showcasing the superiority of this multi-modal liquid biopsy compared to needle biopsy for predicting disease progression. This proof of concept highlights the utility of serum EV analytics as a companion diagnostic test with prognostic utility, which may obviate the need for biopsy., (© 2021 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles.)

Published
2021
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7. Urinary extracellular vesicles: A position paper by the Urine Task Force of the International Society for Extracellular Vesicles.

Author

Erdbrügger U, Blijdorp CJ, Bijnsdorp IV, Borràs FE, Burger D, Bussolati B, Byrd JB, Clayton A, Dear JW, Falcón-Pérez JM, Grange C, Hill AF, Holthöfer H, Hoorn EJ, Jenster G, Jimenez CR, Junker K, Klein J, Knepper MA, Koritzinsky EH, Luther JM, Lenassi M, Leivo J, Mertens I, Musante L, Oeyen E, Puhka M, van Royen ME, Sánchez C, Soekmadji C, Thongboonkerd V, van Steijn V, Verhaegh G, Webber JP, Witwer K, Yuen PST, Zheng L, Llorente A, and Martens-Uzunova ES

Subjects
Advisory Committees, Body Fluids metabolism, Extracellular Vesicles genetics, Extracellular Vesicles metabolism, Humans, Kidney, Reference Standards, Reproducibility of Results, Societies, Urine, Biomarkers urine, Extracellular Vesicles physiology, Urinary Tract pathology
Abstract

Urine is commonly used for clinical diagnosis and biomedical research. The discovery of extracellular vesicles (EV) in urine opened a new fast-growing scientific field. In the last decade urinary extracellular vesicles (uEVs) were shown to mirror molecular processes as well as physiological and pathological conditions in kidney, urothelial and prostate tissue. Therefore, several methods to isolate and characterize uEVs have been developed. However, methodological aspects of EV separation and analysis, including normalization of results, need further optimization and standardization to foster scientific advances in uEV research and a subsequent successful translation into clinical practice. This position paper is written by the Urine Task Force of the Rigor and Standardization Subcommittee of ISEV consisting of nephrologists, urologists, cardiologists and biologists with active experience in uEV research. Our aim is to present the state of the art and identify challenges and gaps in current uEV-based analyses for clinical applications. Finally, recommendations for improved rigor, reproducibility and interoperability in uEV research are provided in order to facilitate advances in the field., (© 2021 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles.)

Published
2021
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8. Pro-Inflammatory Priming of Umbilical Cord Mesenchymal Stromal Cells Alters the Protein Cargo of Their Extracellular Vesicles.

Author

Hyland M, Mennan C, Wilson E, Clayton A, and Kehoe O

Subjects
Biomarkers metabolism, Cells, Cultured, Cytokines metabolism, Humans, Cell Proliferation physiology, Extracellular Vesicles metabolism, Mesenchymal Stem Cells cytology, Umbilical Cord cytology
Abstract

Umbilical cord mesenchymal stromal cells (UCMSCs) have shown an ability to modulate the immune system through the secretion of paracrine mediators, such as extracellular vesicles (EVs). However, the culture conditions that UCMSCs are grown in can alter their secretome and thereby affect their immunomodulatory potential. UCMSCs are commonly cultured at 21% O 2 in vitro, but recent research is exploring their growth at lower oxygen conditions to emulate circulating oxygen levels in vivo. Additionally, a pro-inflammatory culture environment is known to enhance UCMSC anti-inflammatory potential. Therefore, this paper examined EVs from UCMSCs grown in normal oxygen (21% O 2 ), low oxygen (5% O 2 ) and pro-inflammatory conditions to see the impact of culture conditions on the EV profile. EVs were isolated from UCMSC conditioned media and characterised based on size, morphology and surface marker expression. EV protein cargo was analysed using a proximity-based extension assay. Results showed that EVs had a similar size and morphology. Differences were found in EV protein cargo, with pro-inflammatory primed EVs showing an increase in proteins associated with chemotaxis and angiogenesis. This showed that the UCMSC culture environment could alter the EV protein profile and might have downstream implications for their functions in immunomodulation.

Published
2020
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10. Extracellular vesicles as modulators of the cancer microenvironment.

Author

Webber J, Yeung V, and Clayton A

Subjects
Animals, Extracellular Vesicles pathology, Humans, Mesenchymal Stem Cells metabolism, Neovascularization, Pathologic metabolism, Tumor Escape, Extracellular Vesicles chemistry, Tumor Microenvironment
Abstract

The tumour microenvironment is a highly complex and dynamic tissue. It comprises not only neoplastic cells, but also other resident cells within the milieu such as stroma and vascular cells in addition to a variable cellular infiltrate from the periphery. A host of soluble factors such as growth factors, chemokines, eicosanoids soluble metabolites and extracellular matrix components have been extensively documented as factors which modulate this environment. However, in recent years there has also been growing interests in the potential roles of extracellular vesicles (EV) in many of the processes governing the nature of cancerous tissue. In this brief review, we have assembled evidence describing several distinct functions for extracellular vesicles in modulating the microenvironment with examples that include immune evasion, angiogenesis and stromal activation. Whilst there remains a great deal to be learnt about the interplay between vesicles and the cancerous environment, it is becoming clear that vesicle-mediated communication has a major influence on key aspects of cancer growth and progression. We conclude that the design of future therapeutics should acknowledge the existence and roles of extracellular vesicles, and seriously consider strategies for circumventing their effects in vivo., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Published
2015
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11. 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, Zavec, Apolonija Bedina, 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, Chaudhuri, Amrita Datta, 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, Rubio, Ana Paula Dominguez, Dominici, Massimo, Dourado, Mauricio R, Driedonks, Tom AP, Duarte, Filipe V, Duncan, Heather M, Eichenberger, Ramon M, Ekström, Karin, Andaloussi, Samir EL, Elie‐Caille, Celine, Erdbrügger, Uta, Falcón‐Pérez, Juan M, Fatima, Farah, Fish, Jason E, Flores‐Bellver, Miguel, Försönits, András, and Frelet‐Barrand, Annie

Subjects
Biochemistry and Cell Biology, Biological Sciences, extracellular vesicles, exosomes, ectosomes, microvesicles, minimal information requirements, guidelines, standardization, microparticles, rigor, reproducibility, Biochemistry and cell biology
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

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

Author

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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13. Considerations towards a roadmap for collection, handling and storage of blood extracellular vesicles.

Author

Clayton, Aled, Boilard, Eric, Buzas, Edit I, Cheng, Lesley, Falcón-Perez, Juan Manual, Gardiner, Chris, Gustafson, Dakota, Gualerzi, Alice, Hendrix, An, Hoffman, Andrew, Jones, Jennifer, Lässer, Cecilia, Lawson, Charlotte, Lenassi, Metka, Nazarenko, Irina, O'Driscoll, Lorraine, Pink, Ryan, Siljander, Pia R-M, Soekmadji, Carolina, and Wauben, Marca

Subjects
*BODY fluids, *BLOOD, *HEMORHEOLOGY, *EXTRACELLULAR vesicles, *COMPLEX fluids, *TEAMS in the workplace, *REPRODUCIBLE research
Abstract

There is an increasing interest in exploring clinically relevant information that is present in body fluids, and extracellular vesicles (EVs) are intrinsic components of body fluids ("liquid biopsies"). In this report, we will focus on blood. Blood contains not only EVs but also cells, and non-EV particles including lipoproteins. Due to the high concentration of soluble proteins and lipoproteins, blood, plasma and serum have a high viscosity and density, which hampers the concentration, isolation and detection of EVs. Because most if not all studies on EVs are single-centre studies, their clinical relevance remains limited. Therefore, there is an urgent need to improve standardization and reproducibility of EV research. As a first step, the International Society on Extracellular Vesicles organized a biomarker workshop in Birmingham (UK) in November 2017, and during that workshop several working groups were created to focus on a particular body fluid. This report is the first output of the blood EV work group and is based on responses by work group members to a questionnaire in order to discover the contours of a roadmap. From the answers it is clear that most respondents are in favour of evidence-based research, education, quality control procedures, and physical models to improve our understanding and comparison of concentration, isolation and detection methods. Since blood is such a complex body fluid, we assume that the outcome of the survey may also be valuable for exploring body fluids other than blood. [ABSTRACT FROM AUTHOR]

Published
2019
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14. How pure are your vesicles?

Author

Webber, Jason and Clayton, Aled

Subjects
*VESICLES (Cytology), *PROTEINS, *BIOLOGICAL assay, *NANOPARTICLES, *COLORIMETRY
Abstract

We propose a straightforward method to estimate the purity of vesicle preparations by comparing the ratio of nano-vesicle counts to protein concentration, using tools such as the increasingly available NanoSight platform and a colorimetric protein assay such as the BCA-assay. Such an approach is simple enough to apply to every vesicle preparation within a given laboratory, assisting researchers as a routine quality control step. Also, the approach may aid in comparing/standardising vesicle purity across diverse studies, and may be of particular importance in evaluating vesicular biomarkers. We herein propose some criteria to aid in the definition of pure vesicles. [ABSTRACT FROM AUTHOR]

Published
2013
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15. Prostate Cancer Cell Extracellular Vesicles Increase Mineralisation of Bone Osteoblast Precursor Cells in an In Vitro Model.

Author

Lanning, Ben, Webber, Jason, Uysal-Onganer, Pinar, Jiang, Wen Guo, Clayton, Aled, and Dart, Dafydd Alwyn

Subjects
EXTRACELLULAR vesicles, CANCER cells, PROSTATE cancer, BONE cells, BONE metastasis
Abstract

Simple Summary: Prostate cancer frequently metastasizes to the bone, where it forms primarily osteoblastic lesions. Currently there is no real therapeutic option for this late stage of disease, and understanding prostate cancer-bone interaction and communication is vital. Using a simple in vitro model of os-teoblast differentiation and mineralization, we studied this interaction and observed that prostate cancer cells secreted large quantities of extracellular vesicles containing microRNAs. When ex-posed to the extracellular vesicles, increased osteoblast differentiation and mineralization could be observed, and upon RNA-seq several of these microRNAs were implicated as upstream regulators of the mineralization process. These microRNAs also correlated with poor survival in online analysis of patient datasets. We characterized and validated four genes known to be targeted by microRNA-16, and found that extracellular vesicles could deliver miR-16, and increase minerali-zation. Skeletal metastases are the most common form of secondary tumour associated with prostate cancer (PCa). The aberrant function of bone cells neighbouring these tumours leads to the devel-opment of osteoblastic lesions. Communication between PCa cells and bone cells in bone envi-ronments governs both the formation/development of the associated lesion, and growth of the secondary tumour. Using osteoblasts as a model system, we observed that PCa cells and their conditioned medium could stimulate and increase mineralisation and osteoblasts' differentiation. Secreted factors within PCa-conditioned medium responsible for osteoblastic changes included small extracellular vesicles (sEVs), which were sufficient to drive osteoblastogenesis. Using MiR-seq, we profiled the miRNA content of PCa sEVs, showing that miR-16-5p was highly ex-pressed. MiR-16 was subsequently higher in EV-treated 7F2 cells and a miR-16 mimic could also stimulate mineralisation. Next, using RNA-seq of extracellular vesicle (EV)-treated 7F2 cells, we observed a large degree of gene downregulation and an increased mineralisation. Ingenuity® Pathway Analysis (IPA®) revealed that miR-16-5p (and other miRs) was a likely upstream effec-tor. MiR-16-5p targets in 7F2 cells, possibly involved in osteoblastogenesis, were included for val-idation, namely AXIN2, PLSCR4, ADRB2 and DLL1. We then confirmed the targeting and dow-regulation of these genes by sEV miR-16-5p using luciferase UTR (untranslated region) reporters. Conversely, the overexpression of PLSCR4, ADRB2 and DLL1 lead to decreased osteoblastogene-sis. These results indicate that miR-16 is an inducer of osteoblastogenesis and is transmitted through prostate cancer-derived sEVs. The mechanism is a likely contributor towards the for-mation of osteoblastic lesions in metastatic PCa. [ABSTRACT FROM AUTHOR]

Published
2021
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16. Summary of the ISEV workshop on extracellular vesicles as disease biomarkers, held in Birmingham, UK, during December 2017.

Author

Clayton, Aled, Buschmann, Dominik, Byrd, J. Brian, Carter, David R. F., Cheng, Lesley, Compton, Carolyn, Daaboul, George, Devitt, Andrew, Falcon-Perez, Juan Manuel, Gardiner, Chris, Gustafson, Dakota, Harrison, Paul, Helmbrecht, Clemens, Hendrix, An, Hill, Andrew, Hoffman, Andrew, Jones, Jennifer C., Kalluri, Raghu, Kang, Ji Yoon, and Kirchner, Benedikt

Subjects
*VESICLES (Cytology), *BIOMARKERS, *EXOSOMES
Abstract

This report summarises the presentations and activities of the ISEV Workshop on extracellular vesicle biomarkers held in Birmingham, UK during December 2017. Among the key messages was broad agreement about the importance of biospecimen science. Much greater attention needs to be paid towards the provenance of collected samples. The workshop also highlighted clear gaps in our knowledge about pre-analytical factors that alter extracellular vesicles (EVs). The future utility of certified standards for credentialing of instruments and software, to analyse EV and for tracking the influence of isolation steps on the structure and content of EVs were also discussed. Several example studies were presented, demonstrating the potential utility for EVs in disease diagnosis, prognosis, longitudinal serial testing and stratification of patients. The conclusion of the workshop was that more effort focused on pre-analytical issues and benchmarking of isolation methods is needed to strengthen collaborations and advance more effective biomarkers. [ABSTRACT FROM AUTHOR]

Published
2018
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17. Cerebrospinal fluid extracellular vesicle enrichment for protein biomarker discovery in neurological disease; multiple sclerosis.

Author

Welton, Joanne L., Loveless, Samantha, Stone, Timothy, von Ruhland, Chris, Robertson, Neil P., and Clayton, Aled

Subjects
CEREBROSPINAL fluid, NEUROLOGICAL disorders, VESICLES (Cytology), GEL permeation chromatography, PROTEOMICS, MULTIPLE sclerosis
Abstract

The discovery of disease biomarkers, along with the use of “liquid biopsies” as a minimally invasive source of biomarkers, continues to be of great interest. In inflammatory diseases of the central nervous system (CNS), cerebrospinal fluid (CSF) is the most obvious biofluid source. Extracellular vesicles (EVs) are also present in CSF and are thought to be potential “biomarker treasure chests”. However, isolating these CSF-derived EVs remains challenging. This small-scale pilot study developed and tested a protocol to enrich for CSF-EVs, both in relapsing remitting multiple sclerosis (RRMS) CSF and controls. These were subsequently compared, using an aptamer based proteomics array, SOMAscan™. EVs were enriched from RRMS patient (n = 4) and non-demyelinating control (idiopathic intracranial hypertension (IIH) (n = 3)) CSF using precipitation and mini size-exclusion chromatography (SEC). EV-enriched fractions were selected using pre-defined EV characteristics, including increased levels of tetraspanins. EVs and paired CSF were analysed by SOMAscan™, providing relative abundance data for 1128 proteins. CSF-EVs were characterised, revealing exosome-like features: rich in tetraspanins CD9 and CD81, size ~100 nm, and exosome-like morphology by TEM. Sufficient quantities of, SOMAscan™ compatible, EV material was obtained from 5 ml CSF for proteomics analysis. Overall, 348 and 580 proteins were identified in CSF-EVs and CSF, respectively, of which 50 were found to be significantly (t-test) and exclusively enriched in RRMS CSF-EVs. Selected proteins, Plasma kallikrein and Apolipoprotein-E4, were further validated by western blot and appeared increased in CSF-EVs compared to CSF. Functional enrichment analysis of the 50 enriched proteins revealed strong associations with biological processes relating to MS pathology and also extracellular regions, consistent with EV enrichment. This pilot study demonstrates practicality for EV enrichment in CSF derived from patients with MS and controls, allowing detailed analysis of protein profiles that may offer opportunities to identify novel biomarkers and therapeutic approaches in CNS inflammatory diseases. [ABSTRACT FROM PUBLISHER]

Published
2017
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18. A novel community driven software for functional enrichment analysis of extracellular vesicles data.

Author

Pathan, Mohashin, Keerthikumar, Shivakumar, Chisanga, David, Alessandro, Riccardo, Ang, Ching-Seng, Askenase, Philip, Batagov, Arsen O., Benito-Martin, Alberto, Camussi, Giovanni, Clayton, Aled, Collino, Federica, Di Vizio, Dolores, Falcon-Perez, Juan Manuel, Fonseca, Pedro, Fonseka, Pamali, Fontana, Simona, Gho, Yong Song, Hendrix, An, Hoen, Esther Nolte-'t, and Iraci, Nunzio

Subjects
BIOINFORMATICS software, VESICLES (Cytology), RNA sequencing, PROTEIN expression, METABOLOMICS
Abstract

Bioinformatics tools are imperative for the in depth analysis of heterogeneous high-throughput data. Most of the software tools are developed by specific laboratories or groups or companies wherein they are designed to perform the required analysis for the group. However, such software tools may fail to capture “what the community needs in a tool”. Here, we describe a novel community-driven approach to build a comprehensive functional enrichment analysis tool. Using the existing FunRich tool as a template, we invited researchers to request additional features and/or changes. Remarkably, with the enthusiastic participation of the community, we were able to implement 90% of the requested features. FunRich enables plugin for extracellular vesicles wherein users can download and analyse data from Vesiclepedia database. By involving researchers early through community needs software development, we believe that comprehensive analysis tools can be developed in various scientific disciplines. [ABSTRACT FROM PUBLISHER]

Published
2017
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19. Integration of proteomic and metabolomic analysis reveal distinct metabolic alterations of prostate cancer-associated fibroblasts compared to normal fibroblasts from patient's stroma samples.

Author

Bordanaba-Florit, Guillermo, Royo, Félix, Albóniga, Oihane E., Clayton, Aled, Falcón-Pérez, Juan Manuel, and Webber, Jason

Subjects
*FIBROBLASTS, *METABOLOMICS, *RESPIRATION, *EXTRACELLULAR vesicles, *PROSTATE, *LIPID metabolism
Abstract

The prostate gland is a complex and heterogeneous organ composed of epithelium and stroma. Whilst many studies into prostate cancer focus on epithelium, the stroma is known to play a key role in disease with the emergence of a cancer-associated fibroblasts (CAF) phenotype associated upon disease progression. In this work, we studied the metabolic rewiring of stromal fibroblasts following differentiation to a cancer-associated, myofibroblast-like, phenotype. We determined that CAFs were metabolically more active compared to normal fibroblasts. This corresponded with a heightened lipogenic metabolism, as both reservoir species and building block compounds. Interestingly, lipid metabolism affects mitochondria functioning yet the mechanisms of lipid-mediated functions are unclear. Data showing oxidised fatty acids and glutathione system are elevated in CAFs, compared to normal fibroblasts, strengthens the hypothesis that increased metabolic activity is related to mitochondrial activity. This manuscript describes mechanisms responsible for the altered metabolic flux and shows that prostate cancer-derived extracellular vesicles can increase basal respiration in normal fibroblasts, mirroring that of the disease-like phenotype. This indicates that extracellular vesicles derived from prostate cancer cells may drive an altered oxygen-dependent metabolism associated to mitochondria in CAFs. [Display omitted] • Lipogenic metabolic pathways are more prevalent in CAFs. • Energy producing pathways alternative to glycolysis support CAFs metabolic activity. • Mitochondrial metabolism is altered in fibroblast differentiation towards myofibroblasts. • Extracellular vesicles provoke a higher basal respiration associated to mitochondria in normal fibroblasts. [ABSTRACT FROM AUTHOR]

Published
2024
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