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1. Antibody-displaying extracellular vesicles for targeted cancer therapy

Author

Wiklander, Oscar P. B., Mamand, Doste R., Mohammad, Dara K., Zheng, Wenyi, Jawad Wiklander, Rim, Sych, Taras, Zickler, Antje M., Liang, Xiuming, Sharma, Heena, Lavado, Andrea, Bost, Jeremy, Roudi, Samantha, Corso, Giulia, Lennaárd, Angus J., Abedi-Valugerdi, Manuchehr, Mäger, Imre, Alici, Evren, Sezgin, Erdinc, Nordin, Joel Z., Gupta, Dhanu, Görgens, André, and EL Andaloussi, Samir

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

Author

Groß, Rüdiger, Reßin, Hanna, von Maltitz, Pascal, Albers, Dan, Schneider, Laura, Bley, Hanna, Hoffmann, Markus, Cortese, Mirko, Gupta, Dhanu, Deniz, Miriam, Choi, Jae-Yeon, Jansen, Jenny, Preußer, Christian, Seehafer, Kai, Pöhlmann, Stefan, Voelker, Dennis R., Goffinet, Christine, Pogge-von Strandmann, Elke, Bunz, Uwe, Bartenschlager, Ralf, El Andaloussi, Samir, Sparrer, Konstantin M. J., Herker, Eva, Becker, Stephan, Kirchhoff, Frank, Münch, Jan, and Müller, Janis A.

Published
2024
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12. A report on the International Society for Cell & Gene Therapy 2022 Scientific Signature Series, “Therapeutic advances with native and engineered human extracellular vesicles”

Author

Toh, Wei Seong, Yarani, Reza, El Andaloussi, Samir, Cho, Byong Seung, Choi, Chulhee, Corteling, Randolph, De Fougerolles, Antonin, Gimona, Mario, Herz, Josephine, Khoury, Maroun, Robbins, Paul D., Williams, Douglas, Weiss, Daniel J., Rohde, Eva, Giebel, Bernd, and Lim, Sai Kiang

Published
2023
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15. Phenotype-Agnostic Molecular Subtyping of Neurodegenerative Disorders: The Cincinnati Cohort Biomarker Program (CCBP).

Author

Sturchio, Andrea, Marsili, Luca, Vizcarra, Joaquin A, Dwivedi, Alok K, Kauffman, Marcelo A, Duker, Andrew P, Lu, Peixin, Pauciulo, Michael W, Wissel, Benjamin D, Hill, Emily J, Stecher, Benjamin, Keeling, Elizabeth G, Vagal, Achala S, Wang, Lily, Haslam, David B, Robson, Matthew J, Tanner, Caroline M, Hagey, Daniel W, El Andaloussi, Samir, Ezzat, Kariem, Fleming, Ronan MT, Lu, Long J, Little, Max A, and Espay, Alberto J

Subjects
Alzheimer’s disease, Parkinson’s disease, bioassay, biomarkers, cohort, drug repurposing, neurodegeneration, Parkinson's disease, Alzheimer's disease, Biochemistry and Cell Biology, Neurosciences, Cognitive Sciences
Abstract

Ongoing biomarker development programs have been designed to identify serologic or imaging signatures of clinico-pathologic entities, assuming distinct biological boundaries between them. Identified putative biomarkers have exhibited large variability and inconsistency between cohorts, and remain inadequate for selecting suitable recipients for potential disease-modifying interventions. We launched the Cincinnati Cohort Biomarker Program (CCBP) as a population-based, phenotype-agnostic longitudinal study. While patients affected by a wide range of neurodegenerative disorders will be deeply phenotyped using clinical, imaging, and mobile health technologies, analyses will not be anchored on phenotypic clusters but on bioassays of to-be-repurposed medications as well as on genomics, transcriptomics, proteomics, metabolomics, epigenomics, microbiomics, and pharmacogenomics analyses blinded to phenotypic data. Unique features of this cohort study include (1) a reverse biology-to-phenotype direction of biomarker development in which clinical, imaging, and mobile health technologies are subordinate to biological signals of interest; (2) hypothesis free, causally- and data driven-based analyses; (3) inclusive recruitment of patients with neurodegenerative disorders beyond clinical criteria-meeting patients with Parkinson's and Alzheimer's diseases, and (4) a large number of longitudinally followed participants. The parallel development of serum bioassays will be aimed at linking biologically suitable subjects to already available drugs with repurposing potential in future proof-of-concept adaptive clinical trials. Although many challenges are anticipated, including the unclear pathogenic relevance of identifiable biological signals and the possibility that some signals of importance may not yet be measurable with current technologies, this cohort study abandons the anchoring role of clinico-pathologic criteria in favor of biomarker-driven disease subtyping to facilitate future biosubtype-specific disease-modifying therapeutic efforts.

Published
2020

17. mRNA-LNP vaccines tuned for systemic immunization induce strong antitumor immunity by engaging splenic immune cells

Author

Bevers, Sanne, Kooijmans, Sander A.A., Van de Velde, Elien, Evers, Martijn J.W., Seghers, Sofie, Gitz-Francois, Jerney J.J.M., van Kronenburg, Nicky C.H., Fens, Marcel H.A.M., Mastrobattista, Enrico, Hassler, Lucie, Sork, Helena, Lehto, Taavi, Ahmed, Kariem E., El Andaloussi, Samir, Fiedler, Katja, Breckpot, Karine, Maes, Michael, Van Hoorick, Diane, Bastogne, Thierry, Schiffelers, Raymond M., and De Koker, Stefaan

Published
2022
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20. Novel endosomolytic compounds enable highly potent delivery of antisense oligonucleotides

Author

Bost, Jeremy P., Ojansivu, Miina, Munson, Michael J., Wesén, Emelie, Gallud, Audrey, Gupta, Dhanu, Gustafsson, Oskar, Saher, Osama, Rädler, Julia, Higgins, Stuart G., Lehto, Taavi, Holme, Margaret N., Dahlén, Anders, Engkvist, Ola, Strömstedt, Per-Erik, Andersson, Shalini, Edvard Smith, C. I., Stevens, Molly M., Esbjörner, Elin K., Collén, Anna, and El Andaloussi, Samir

Published
2022
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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, 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, and Frelet-Barrand, Annie

Subjects
ectosomes, exosomes, extracellular vesicles, guidelines, microparticles, microvesicles, minimal information requirements, reproducibility, rigor, standardization, 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

23. Amelioration of systemic inflammation via the display of two different decoy protein receptors on extracellular vesicles

Author

Gupta, Dhanu, Wiklander, Oscar P. B., Görgens, André, Conceição, Mariana, Corso, Giulia, Liang, Xiuming, Seow, Yiqi, Balusu, Sriram, Feldin, Ulrika, Bostancioglu, Beklem, Jawad, Rim, Mamand, Doste R., Lee, Yi Xin Fiona, Hean, Justin, Mäger, Imre, Roberts, Thomas C., Gustafsson, Manuela, Mohammad, Dara K., Sork, Helena, Backlund, Alexandra, Lundin, Per, de Fougerolles, Antonin, Smith, C. I. Edvard, Wood, Matthew J. A., Vandenbroucke, Roosmarijn E., Nordin, Joel Z., and El-Andaloussi, Samir

Published
2021
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24. Novel Endogenous Engineering Platform for Robust Loading and Delivery of Functional mRNA by Extracellular Vesicles.

Author

Zickler, Antje M., Liang, Xiuming, Gupta, Dhanu, Mamand, Doste R., De Luca, Mariacristina, Corso, Giulia, Errichelli, Lorenzo, Hean, Justin, Sen, Titash, Elsharkasy, Omnia M., Kamei, Noriyasu, Niu, Zheyu, Zhou, Guannan, Zhou, Houze, Roudi, Samantha, Wiklander, Oscar P. B., Görgens, André, Nordin, Joel Z., Castilla‐Llorente, Virginia, and EL Andaloussi, Samir

Subjects
VESICULAR stomatitis, EXTRACELLULAR vesicles, NUCLEIC acids, BIOENGINEERING, IMMUNE response
Abstract

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

Published
2024
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27. A modular strategy for extracellular vesicle-mediated CRISPR-Cas9 delivery through aptamer-based loading and UV-activated cargo release

Author

Elsharkasy, Omnia M., primary, Hegeman, Charlotte V., additional, Lansweers, Ivana, additional, Cotugno, Olaf L., additional, de Groot, Ingmar Y., additional, de Wit, Zoe E.N.M.J., additional, Liang, Xiuming, additional, Garcia-Guerra, Antonio, additional, Moorman, Niels J.A., additional, Lefferts, Julliet, additional, de Voogt, Willemijn S., additional, Gitz-Francois, Jerney J., additional, van Wesel, Annet C.W., additional, El Andaloussi, Samir, additional, Schiffelers, Raymond M., additional, Kooijmans, Sander A.A., additional, Mastrobattista, Enrico, additional, Vader, Pieter, additional, and de Jong, Olivier G., additional

Published
2024
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28. Snorkel-tag Based Affinity Chromatography for Recombinant Extracellular Vesicle Purification

Author

Bobbili, Madhusudhan Reddy, primary, Gorgens, Andre, additional, Yan, Yan, additional, Vogt, Stefan, additional, Gupta, Dhanu, additional, Corso, Giulia, additional, Barbaria, Samir, additional, Patrioli, Carolina, additional, Weilner, Sylvia, additional, Pultar, Marianne, additional, Jacak, Jaroslaw, additional, Hackl, Matthias, additional, Schosserer, Markus, additional, Grillari, Regina, additional, Kjems, Jorgen, additional, EL Andaloussi, Samir, additional, and Grillari, Johannes, additional

Published
2024
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29. Exosomes are vehicles for the stress-regulated secretion of histones

Author

Singh, Birendra, primary, Sundbom, Marcus Fredriksson, additional, Muthukrishnan, Uma, additional, Natarajan, Balasubramanian, additional, Stransky, Stephanie, additional, Görgens, André, additional, Nordin, Joel Z., additional, Wiklander, Oscar P. B., additional, Sandblad, Linda, additional, Sidoli, Simone, additional, EL Andaloussi, Samir, additional, Haney, Michael, additional, and Gilthorpe, Jonathan D., additional

Published
2024
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30. Mesenchymal stem cell-based therapy for ischemic stroke

Author

Anderson, Johnathon D, Pham, Missy T, Contreras, Zelenia, Hoon, Madeline, Fink, Kyle D, Johansson, Henrik J, Rossignol, Julien, Dunbar, Gary L, Showalter, Megan, Fiehn, Oliver, Bramlett, Charles S, Bardini, Renee L, Bauer, Gerhard, Fury, Brian, Hendrix, Kyle J, Chedin, Frederic, EL-Andaloussi, Samir, Hwang, Billianna, Mulligan, Michael S, Lehtiö, Janne, and Nolta, Jan A

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

© 2016 The Author(s). Ischemic stroke represents a major, worldwide health burden with increasing incidence. Patients affected by ischemic strokes currently have few clinically approved treatment options available. Most currently approved treatments for ischemic stroke have narrow therapeutic windows, severely limiting the number of patients able to be treated. Mesenchymal stem cells represent a promising novel treatment for ischemic stroke. Numerous studies have demonstrated that mesenchymal stem cells functionally improve outcomes in rodent models of ischemic stroke. Recent studies have also shown that exosomes secreted by mesenchymal stem cells mediate much of this effect. In the present review, we summarize the current literature on the use of mesenchymal stem cells to treat ischemic stroke. Further studies investigating the mechanisms underlying mesenchymal stem cells tissue healing effects are warranted and would be of benefit to the field.

Published
2016

31. Comprehensive Proteomic Analysis of Mesenchymal Stem Cell Exosomes Reveals Modulation of Angiogenesis via Nuclear Factor-KappaB Signaling.

Author

Anderson, Johnathon D, Johansson, Henrik J, Graham, Calvin S, Vesterlund, Mattias, Pham, Missy T, Bramlett, Charles S, Montgomery, Elizabeth N, Mellema, Matt S, Bardini, Renee L, Contreras, Zelenia, Hoon, Madeline, Bauer, Gerhard, Fink, Kyle D, Fury, Brian, Hendrix, Kyle J, Chedin, Frederic, El-Andaloussi, Samir, Hwang, Billie, Mulligan, Michael S, Lehtiö, Janne, and Nolta, Jan A

Subjects
Bone Marrow Cells, Mesenchymal Stem Cells, Humans, NF-kappa B, Proteome, Paracrine Communication, Signal Transduction, Gene Expression Regulation, Developmental, Neovascularization, Physiologic, Male, Exosomes, Young Adult, High-resolution isoelectric focusing, Liquid chromatography tandem mass spectrometry, Mesenchymal stem cells, Nuclear factor kappaB, Peripheral arterial disease, Proteomics, Gene Expression Regulation, Developmental, Neovascularization, Physiologic, Regenerative Medicine, Stem Cell Research - Nonembryonic - Human, Biotechnology, Stem Cell Research - Nonembryonic - Non-Human, Transplantation, Stem Cell Research, 5.2 Cellular and gene therapies, Mesenchymal Stromal Cells, Immunology, Biological Sciences, Technology, Medical and Health Sciences
Abstract

Mesenchymal stem cells (MSC) are known to facilitate healing of ischemic tissue related diseases through proangiogenic secretory proteins. Recent studies further show that MSC derived exosomes function as paracrine effectors of angiogenesis, however, the identity of which components of the exosome proteome responsible for this effect remains elusive. To address this we used high-resolution isoelectric focusing coupled liquid chromatography tandem mass spectrometry, an unbiased high throughput proteomics approach to comprehensively characterize the proteinaceous contents of MSCs and MSC derived exosomes. We probed the proteome of MSCs and MSC derived exosomes from cells cultured under expansion conditions and under ischemic tissue simulated conditions to elucidate key angiogenic paracrine effectors present and potentially differentially expressed in these conditions. In total, 6,342 proteins were identified in MSCs and 1,927 proteins in MSC derived exosomes, representing to our knowledge the first time these proteomes have been probed comprehensively. Multilayered analyses identified several putative paracrine effectors of angiogenesis present in MSC exosomes and increased in expression in MSCs exposed to ischemic tissue-simulated conditions; these include platelet derived growth factor, epidermal growth factor, fibroblast growth factor, and most notably nuclear factor-kappaB (NFkB) signaling pathway proteins. NFkB signaling was identified as a key mediator of MSC exosome induced angiogenesis in endothelial cells by functional in vitro validation using a specific inhibitor. Collectively, the results of our proteomic analysis show that MSC derived exosomes contain a robust profile of angiogenic paracrine effectors, which have potential for the treatment of ischemic tissue-related diseases.

Published
2016

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

Author

Nguyen, Vivian V.T., Welsh, Joshua A., Tertel, Tobias, Choo, Andre, van de Wakker, Simonides I., Defourny, Kyra A.Y., Giebel, Bernd, Vader, Pieter, Padmanabhan, Jayanthi, Lim, Sai Kiang, Nolte-'t Hoen, Esther N.M., Verhaar, Marianne C., Bostancioglu, R. Beklem, Zickler, Antje M., Hong, Jia Mei, Jones, Jennifer C., EL Andaloussi, Samir, van Balkom, Bas W.M., Görgens, André, Nguyen, Vivian V.T., Welsh, Joshua A., Tertel, Tobias, Choo, Andre, van de Wakker, Simonides I., Defourny, Kyra A.Y., Giebel, Bernd, Vader, Pieter, Padmanabhan, Jayanthi, Lim, Sai Kiang, Nolte-'t Hoen, Esther N.M., Verhaar, Marianne C., Bostancioglu, R. Beklem, Zickler, Antje M., Hong, Jia Mei, Jones, Jennifer C., EL Andaloussi, Samir, van Balkom, Bas W.M., and Görgens, André

Abstract

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

Published
2024

34. Size matters: Functional differences of small extracellular vesicle subpopulations in cardiac repair responses

Author

van de Wakker, Simonides Immanuel, Bauzá-Martinez, Julia, Ríos Arceo, Carla, Manjikian, Herak, Snijders Blok, Christian Jamie Bernard, Roefs, Marieke Theodora, Willms, Eduard, Maas, Renee Goverdina Catharina, Pronker, Matti Feije, de Jong, Olivier Gerrit, Wu, Wei, Görgens, André, El Andaloussi, Samir, Sluijter, Joost Petrus Gerardus, Vader, Pieter, van de Wakker, Simonides Immanuel, Bauzá-Martinez, Julia, Ríos Arceo, Carla, Manjikian, Herak, Snijders Blok, Christian Jamie Bernard, Roefs, Marieke Theodora, Willms, Eduard, Maas, Renee Goverdina Catharina, Pronker, Matti Feije, de Jong, Olivier Gerrit, Wu, Wei, Görgens, André, El Andaloussi, Samir, Sluijter, Joost Petrus Gerardus, and Vader, Pieter

Abstract

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

Published
2024

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

Author

Cardiologie, CDL Staf Research, CDL Cluster Onderzoek en Onderwijs, Circulatory Health, Zorgeenheid Vaatchirurgie Medisch, UMC Utrecht Holding, Nefro Vasculaire Geneeskunde, Regenerative Medicine and Stem Cells, MS Nefrologie, Nguyen, Vivian V.T., Welsh, Joshua A., Tertel, Tobias, Choo, Andre, van de Wakker, Simonides I., Defourny, Kyra A.Y., Giebel, Bernd, Vader, Pieter, Padmanabhan, Jayanthi, Lim, Sai Kiang, Nolte-'t Hoen, Esther N.M., Verhaar, Marianne C., Bostancioglu, R. Beklem, Zickler, Antje M., Hong, Jia Mei, Jones, Jennifer C., EL Andaloussi, Samir, van Balkom, Bas W.M., Görgens, André, Cardiologie, CDL Staf Research, CDL Cluster Onderzoek en Onderwijs, Circulatory Health, Zorgeenheid Vaatchirurgie Medisch, UMC Utrecht Holding, Nefro Vasculaire Geneeskunde, Regenerative Medicine and Stem Cells, MS Nefrologie, Nguyen, Vivian V.T., Welsh, Joshua A., Tertel, Tobias, Choo, Andre, van de Wakker, Simonides I., Defourny, Kyra A.Y., Giebel, Bernd, Vader, Pieter, Padmanabhan, Jayanthi, Lim, Sai Kiang, Nolte-'t Hoen, Esther N.M., Verhaar, Marianne C., Bostancioglu, R. Beklem, Zickler, Antje M., Hong, Jia Mei, Jones, Jennifer C., EL Andaloussi, Samir, van Balkom, Bas W.M., and Görgens, André

Published
2024

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

Author

Mamand, Doste R., Bazaz, Safa, Mohammad, Dara K., Liang, Xiuming, Pavlova, Svetlana, Mim, Carsten, Gabrielsson, Susanne, Nordin, Joel Z., Wiklander, Oscar P. B., Abedi-Valugerdi, Manuchehr, EL-Andaloussi, Samir, Mamand, Doste R., Bazaz, Safa, Mohammad, Dara K., Liang, Xiuming, Pavlova, Svetlana, Mim, Carsten, Gabrielsson, Susanne, Nordin, Joel Z., Wiklander, Oscar P. B., Abedi-Valugerdi, Manuchehr, and EL-Andaloussi, Samir

Abstract

Haematopoiesis dysregulation with the presence of immature myeloid and erythroid immunosuppressive cells are key characteristics of the immune escape phase of tumour development. Here, the role of in vitro generated B16F10 tumour cell-derived extracellular vesicles (tEVs) as indirect cellular communicators, participating in tumour-induced dysregulation of haematopoiesis, was explored. The isolated tEVs displayed features of small EVs with a size range of 100-200 nm, expressed the common EV markers CD63, CD9, and Alix, and had a spherical shape with a lipid bilayer membrane. Proteomic profiling revealed significant levels of angiogenic factors, particularly vascular endothelial growth factor (VEGF), osteopontin, and tissue factor, associated with the tEVs. Systemic administration of these tEVs in syngeneic mice induced splenomegaly and disrupted haematopoiesis, leading to extramedullary haematopoiesis, expansion of splenic immature erythroid progenitors, reduced bone marrow cellularity, medullary expansion of granulocytic myeloid suppressor cells, and the development of anaemia. These effects closely mirrored those observed in tumour-bearing mice and were not seen after heat inactivating the tEVs. In vitro studies demonstrated that tEVs independently induced the expansion of bone marrow granulocytic myeloid suppressor cells and B cells while reducing the frequency of cells in the erythropoietic lineage. These effects of tEVs were significantly abrogated by the blockade of VEGF or heat inactivation. Our findings underscore the important role of tEVs in dysregulating haematopoiesis during the immune escape phase of cancer immunoediting, suggesting their potential as targets for addressing immune evasion and reinstating normal hematopoietic processes., QC 20240715

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

Author

Afd Biomol.Mass Spect. and Proteomics, Sub Biomol.Mass Spectrometry & Proteom., Afd Pharmaceutics, Sub General Pharmaceutics, van de Wakker, Simonides Immanuel, Bauzá-Martinez, Julia, Ríos Arceo, Carla, Manjikian, Herak, Snijders Blok, Christian Jamie Bernard, Roefs, Marieke Theodora, Willms, Eduard, Maas, Renee Goverdina Catharina, Pronker, Matti Feije, de Jong, Olivier Gerrit, Wu, Wei, Görgens, André, El Andaloussi, Samir, Sluijter, Joost Petrus Gerardus, Vader, Pieter, Afd Biomol.Mass Spect. and Proteomics, Sub Biomol.Mass Spectrometry & Proteom., Afd Pharmaceutics, Sub General Pharmaceutics, van de Wakker, Simonides Immanuel, Bauzá-Martinez, Julia, Ríos Arceo, Carla, Manjikian, Herak, Snijders Blok, Christian Jamie Bernard, Roefs, Marieke Theodora, Willms, Eduard, Maas, Renee Goverdina Catharina, Pronker, Matti Feije, de Jong, Olivier Gerrit, Wu, Wei, Görgens, André, El Andaloussi, Samir, Sluijter, Joost Petrus Gerardus, and Vader, Pieter

Published
2024

39. Author Correction: GAPDH controls extracellular vesicle biogenesis and enhances the therapeutic potential of EV mediated siRNA delivery to the brain

Author

Dar, Ghulam Hassan, Mendes, Cláudia C., Kuan, Wei-Li, Speciale, Alfina A., Conceição, Mariana, Görgens, André, Uliyakina, Inna, Lobo, Miguel J., Lim, Wooi F., EL Andaloussi, Samir, Mäger, Imre, Roberts, Thomas C., Barker, Roger A., Goberdhan, Deborah C. I., Wilson, Clive, and Wood, Matthew J. A.

Published
2021
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41. Size matters: Functional differences of small extracellular vesicle subpopulations in cardiac repair responses

Author

van de Wakker, Simonides Immanuel, primary, Bauzá‐Martinez, Julia, additional, Ríos Arceo, Carla, additional, Manjikian, Herak, additional, Snijders Blok, Christian Jamie Bernard, additional, Roefs, Marieke Theodora, additional, Willms, Eduard, additional, Maas, Renee Goverdina Catharina, additional, Pronker, Matti Feije, additional, de Jong, Olivier Gerrit, additional, Wu, Wei, additional, Görgens, André, additional, El Andaloussi, Samir, additional, Sluijter, Joost Petrus Gerardus, additional, and Vader, Pieter, additional

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

Author

Nguyen, Vivian V. T., Welsh, Joshua A., Tertel, Tobias, Choo, Andre, van de Wakker, Simonides I., Defourny, Kyra A. Y., Giebel, Bernd, Vader, Pieter, Padmanabhan, Jayanthi, Lim, Sai Kiang, Nolte‐'t Hoen, Esther N. M., Verhaar, Marianne C., Bostancioglu, R. Beklem, Zickler, Antje M., Hong, Jia Mei, Jones, Jennifer C., EL Andaloussi, Samir, van Balkom, Bas W. M., and Görgens, André

Subjects
EXTRACELLULAR vesicles, STROMAL cells, MANUFACTURED products, HIERARCHICAL clustering (Cluster analysis), CD19 antigen, LABORATORIES
Abstract

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

Published
2024
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45. Engineering of extracellular vesicles for efficient intracellular delivery of multimodal therapeutics including genome editors

Author

Liang, Xiuming, primary, Gupta, Dhanu, additional, Xie, Junhua, additional, Wonterghem, Elien, additional, Hoecke, Lien, additional, Hean, Justin, additional, Niu, Zheyu, additional, Wiklander, Oscar, additional, Zheng, Wenyi, additional, Wiklander, Rim, additional, He, Rui, additional, Mammad, Doste, additional, Bost, Jeremy, additional, Zhou, Guannan, additional, Zhou, Houze, additional, Roudi, Samantha, additional, Zickler, Antje, additional, Gorgens, Andre, additional, Hagey, Daniel, additional, de Jong, Olivier G, additional, Uy, Aileen, additional, Zong, Yuanyuan, additional, Mager, Imre, additional, Perez, Carla, additional, Roberts, Thomas, additional, Vader, Pieter, additional, Fougerolles, Antonin, additional, Wood, Matthew, additional, Vandenbroucke, Roosmarijn, additional, Nordin, Joel, additional, and El-Andaloussi, Samir, additional

Published
2023
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47. Role of EVs as promotors for activation of leukemia-derived dendritic cell (DCleu)-mediated antileukemic immune response against AML-blasts

Author

Lin, Li, primary, Görgens, André, additional, Mussack, Veronika, additional, Pepeldjiyska, Elena, additional, Hartz, Anne, additional, Aslan, Hazal, additional, Rackl, Elias, additional, Rank, Andreas, additional, Schmohl, Jörg, additional, Krämer, Doris, additional, El-Andaloussi, Samir, additional, Pfaffl, Michael, additional, and schmetzer, helga, additional

Published
2023
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48. The cellular response to extracellular vesicles is dependent on their cell source and dose

Author

Hagey, Daniel W., primary, Ojansivu, Miina, additional, Bostancioglu, Beklem R., additional, Saher, Osama, additional, Bost, Jeremy P., additional, Gustafsson, Manuela O., additional, Gramignoli, Roberto, additional, Svahn, Mathias, additional, Gupta, Dhanu, additional, Stevens, Molly M., additional, Görgens, André, additional, and EL Andaloussi, Samir, additional

Published
2023
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