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33 results on '"Corso, Giulia"'

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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2. 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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3. Snorkel‐tag based affinity chromatography for recombinant extracellular vesicle purification.

Author

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

Subjects
TRANSMEMBRANE domains, TARGETED drug delivery, EXTRACELLULAR vesicles, AFFINITY chromatography, ELECTRIC vehicle industry
Abstract

Extracellular vesicles (EVs) are lipid nanoparticles and play an important role in cell‐cell communications, making them potential therapeutic agents and allowing to engineer for targeted drug delivery. The expanding applications of EVs in next generation medicine is still limited by existing tools for scaling standardized EV production, single EV tracing and analytics, and thus provide only a snapshot of tissue‐specific EV cargo information. Here, we present the Snorkel‐tag, for which we have genetically fused the EV surface marker protein CD81, to a series of tags with an additional transmembrane domain to be displayed on the EV surface, resembling a snorkel. This system enables the affinity purification of EVs from complex matrices in a non‐destructive form while maintaining EV characteristics in terms of surface protein profiles, associated miRNA patterns and uptake into a model cell line. Therefore, we consider the Snorkel‐tag to be a widely applicable tool in EV research, allowing for efficient preparation of EV standards and reference materials, or dissecting EVs with different surface markers when fusing to other tetraspanins in vitro or in vivo. [ABSTRACT FROM AUTHOR]

Published
2024
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4. 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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5. 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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8. Novel endogenous engineering platform for robust loading and delivery of functional mRNA by extracellular vesicles

Author

Zickler, Antje Maria, primary, Liang, Xiuming, additional, de Luca, Mariacristina, additional, Gupta, Dhanu, additional, Corso, Giulia, additional, Errichelli, Lorenzo, additional, Hean, Justin, additional, Kamei, Noriyasu, additional, Niu, Zheyu, additional, Zhou, Guannan, additional, Roudi, Samantha, additional, Nordin, Joel, additional, Castilla-Llorente, Virginia, additional, and EL Andaloussi, Samir, additional

Published
2023
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10. Identification of storage conditions stabilizing extracellular vesicles preparations

Author

Experimentele Afd. Cardiologie 2, Cardiologie, CDL Cluster Onderzoek en Onderwijs, Circulatory Health, Görgens, André, Corso, Giulia, Hagey, Daniel W., Jawad Wiklander, Rim, Gustafsson, Manuela O., Felldin, Ulrika, Lee, Yi, Bostancioglu, R. Beklem, Sork, Helena, Liang, Xiuming, Zheng, Wenyi, Mohammad, Dara K., van de Wakker, Simonides I., Vader, Pieter, Zickler, Antje M., Mamand, Doste R., Ma, Li, Holme, Margaret N., Stevens, Molly M., Wiklander, Oscar P.B., EL Andaloussi, Samir, Experimentele Afd. Cardiologie 2, Cardiologie, CDL Cluster Onderzoek en Onderwijs, Circulatory Health, Görgens, André, Corso, Giulia, Hagey, Daniel W., Jawad Wiklander, Rim, Gustafsson, Manuela O., Felldin, Ulrika, Lee, Yi, Bostancioglu, R. Beklem, Sork, Helena, Liang, Xiuming, Zheng, Wenyi, Mohammad, Dara K., van de Wakker, Simonides I., Vader, Pieter, Zickler, Antje M., Mamand, Doste R., Ma, Li, Holme, Margaret N., Stevens, Molly M., Wiklander, Oscar P.B., and EL Andaloussi, Samir

Published
2022

11. Identification of storage conditions stabilizing extracellular vesicles preparations

Author

Görgens, André, primary, Corso, Giulia, additional, Hagey, Daniel W., additional, Jawad Wiklander, Rim, additional, Gustafsson, Manuela O., additional, Felldin, Ulrika, additional, Lee, Yi, additional, Bostancioglu, R. Beklem, additional, Sork, Helena, additional, Liang, Xiuming, additional, Zheng, Wenyi, additional, Mohammad, Dara K., additional, van de Wakker, Simonides I., additional, Vader, Pieter, additional, Zickler, Antje M., additional, Mamand, Doste R., additional, Ma, Li, additional, Holme, Margaret N., additional, Stevens, Molly M., additional, Wiklander, Oscar P. B., additional, and EL Andaloussi, Samir, additional

Published
2022
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12. Extracellular vesicles engineered to bind albumin demonstrate extended circulation time and lymph node accumulation in mouse models

Author

Liang, Xiuming, primary, Niu, Zheyu, additional, Galli, Valentina, additional, Howe, Nathalie, additional, Zhao, Ying, additional, Wiklander, Oscar P. B., additional, Zheng, Wenyi, additional, Wiklander, Rim Jawad, additional, Corso, Giulia, additional, Davies, Christopher, additional, Hean, Justin, additional, Kyriakopoulou, Eleni, additional, Mamand, Doste R., additional, Amin, Risul, additional, Nordin, Joel Z., additional, Gupta, Dhanu, additional, and Andaloussi, Samir EL, additional

Published
2022
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13. Growth Media Conditions Influence the Secretion Route and Release Levels of Engineered Extracellular Vesicles

Author

Bost, Jeremy P., primary, Saher, Osama, additional, Hagey, Daniel, additional, Mamand, Doste R., additional, Liang, Xiuming, additional, Zheng, Wenyi, additional, Corso, Giulia, additional, Gustafsson, Oskar, additional, Görgens, André, additional, Smith, CI Edvard, additional, Zain, Rula, additional, El Andaloussi, Samir, additional, and Gupta, Dhanu, additional

Published
2021
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14. Profiling of Extracellular Small RNAs Highlights a Strong Bias towards Non-Vesicular Secretion

Author

Sork, Helena, Conceicao, Mariana, Corso, Giulia, Nordin, Joel, Lee, Yi Xin Fiona, Krjutskov, Kaarel, Orzechowski Westholm, Jakub, Vader, Pieter, Pauwels, Marie, Vandenbroucke, Roosmarijn E., Wood, Matthew J. A., EL Andaloussi, Samir, Mager, Imre, Sork, Helena, Conceicao, Mariana, Corso, Giulia, Nordin, Joel, Lee, Yi Xin Fiona, Krjutskov, Kaarel, Orzechowski Westholm, Jakub, Vader, Pieter, Pauwels, Marie, Vandenbroucke, Roosmarijn E., Wood, Matthew J. A., EL Andaloussi, Samir, and Mager, Imre

Abstract

The extracellular environment consists of a plethora of molecules, including extracellular miRNA that can be secreted in association with extracellular vesicles (EVs) or soluble protein complexes (non-EVs). Yet, interest in therapeutic short RNA carriers lies mainly in EVs, the vehicles conveying the great majority of the biological activity. Here, by overexpressing miRNA and shRNA sequences in parent cells and using size exclusion liquid chromatography (SEC) to separate the secretome into EV and non-EV fractions, we saw that >98% of overexpressed miRNA was secreted within the non-EV fraction. Furthermore, small RNA sequencing studies of native miRNA transcripts revealed that although the abundance of miRNAs in EVs, non-EVs and parent cells correlated well (R-2 = 0.69-0.87), quantitatively an outstanding 96.2-99.9% of total miRNA was secreted in the non-EV fraction. Nevertheless, though EVs contained only a fraction of secreted miRNAs, these molecules were stable at 37 degrees C in a serum-containing environment, indicating that if sufficient miRNA loading is achieved, EVs can remain delivery-competent for a prolonged period of time. This study suggests that the passive endogenous EV loading strategy might be a relatively wasteful way of loading miRNA to EVs, and active miRNA loading approaches are needed for developing advanced EV miRNA therapies in the future.

Published
2021
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15. Profiling of Extracellular Small RNAs Highlights a Strong Bias towards Non-Vesicular Secretion

Author

Centraal Diagnostisch Laboratorium, CDL Nanomedicine, Circulatory Health, Sork, Helena, Conceicao, Mariana, Corso, Giulia, Nordin, Joel, Lee, Yi Xin Fiona, Krjutskov, Kaarel, Orzechowski Westholm, Jakub, Vader, Pieter, Pauwels, Marie, Vandenbroucke, Roosmarijn E., Wood, Matthew Ja, El Andaloussi, Samir, Mäger, Imre, Centraal Diagnostisch Laboratorium, CDL Nanomedicine, Circulatory Health, Sork, Helena, Conceicao, Mariana, Corso, Giulia, Nordin, Joel, Lee, Yi Xin Fiona, Krjutskov, Kaarel, Orzechowski Westholm, Jakub, Vader, Pieter, Pauwels, Marie, Vandenbroucke, Roosmarijn E., Wood, Matthew Ja, El Andaloussi, Samir, and Mäger, Imre

Published
2021

16. Profiling of Extracellular Small RNAs Highlights a Strong Bias towards Non-Vesicular Secretion

Author

Sork, Helena, primary, Conceicao, Mariana, additional, Corso, Giulia, additional, Nordin, Joel, additional, Lee, Yi Xin Fiona, additional, Krjutskov, Kaarel, additional, Orzechowski Westholm, Jakub, additional, Vader, Pieter, additional, Pauwels, Marie, additional, Vandenbroucke, Roosmarijn E., additional, Wood, Matthew JA, additional, EL Andaloussi, Samir, additional, and Mäger, Imre, additional

Published
2021
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17. Quantification of extracellular vesicles in vitro and in vivo using sensitive bioluminescence imaging

Author

Gupta, Dhanu, Liang, Xiuming, Pavlova, Svetlana, Wiklander, Oscar P.B, Corso, Giulia, Zhao, Ying, Saher, Osama, Bost, Jeremy, Zickler, Antje M., Piffko, Andras, Maire, Cecile L., Ricklefs, Franz L., Gustafsson, Oskar, Llorente, Virginia Castilla, Gustafsson, Manuela O., Bostancioglu, R. Beklem, Mamand, Doste R, Hagey, Daniel W., Görgens, André, Nordin, Joel Z., and EL Andaloussi, Samir

Subjects
nanotechnology, evs subpopulation, lcsh:Cytology, drug delivery, Medizin, exosomes, lcsh:QH573-671, extracellular vesicles, biodistribution, bioluminescence, evs labelling, microvesicles, pharmacokinetics
Abstract

Extracellular vesicles (EVs) are naturally occurring nano-sized carriers that are secreted by cells and facilitate cell-to-cell communication by their unique ability to transfer biologically active cargo. Despite the pronounced increase in our understanding of EVs over the last decade, from disease pathophysiology to therapeutic drug delivery, improved molecular tools to track their therapeutic delivery are still needed. Unfortunately, the present catalogue of tools utilised for EV labelling lacks sensitivity or are not sufficiently specific. Here, we have explored the bioluminescent labelling of EVs using different luciferase enzymes tethered to CD63 to achieve a highly sensitive system for in vitro and in vivo tracking of EVs. Using tetraspanin fusions to either NanoLuc or ThermoLuc permits performing highly sensitive in vivo quantification of EVs or real-time imaging, respectively, at low cost and in a semi-high throughput manner. We find that the in vivo distribution pattern of EVs is determined by the route of injection, but that different EV subpopulations display differences in biodistribution patterns. By applying this technology for real-time non-invasive in vivo imaging of EVs, we show that their distribution to different internal organs occurs just minutes after administration. CA extern

Published
2020

18. Profiling of extracellular small RNAs highlights a strong bias towards non-vesicular secretion

Author

Sork, Helena, primary, Conceicao, Mariana, additional, Corso, Giulia, additional, Nordin, Joel, additional, Lee, Yi Xin Fiona, additional, Krjutskov, Kaarel, additional, Westholm, Jakub Orzechowski, additional, Vader, Pieter, additional, Pauwels, Marie, additional, Vandenbroucke, Roosmarijn, additional, Wood, Matthew JA, additional, Andaloussi, Samir EL, additional, and Mäger, Imre, additional

Published
2020
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19. Quantification of extracellular vesicles in vitro and in vivo using sensitive bioluminescence imaging

Author

Gupta, Dhanu, primary, Liang, Xiuming, additional, Pavlova, Svetlana, additional, Wiklander, Oscar P.B, additional, Corso, Giulia, additional, Zhao, Ying, additional, Saher, Osama, additional, Bost, Jeremy, additional, Zickler, Antje M., additional, Piffko, Andras, additional, Maire, Cecile L., additional, Ricklefs, Franz L., additional, Gustafsson, Oskar, additional, Llorente, Virginia Castilla, additional, Gustafsson, Manuela O., additional, Bostancioglu, R. Beklem, additional, Mamand, Doste R, additional, Hagey, Daniel W., additional, Görgens, André, additional, Nordin, Joel Z., additional, and EL Andaloussi, Samir, additional

Published
2020
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20. Engineering of extracellular vesicles for display of protein biotherapeutics

Author

Gupta, Dhanu, primary, Wiklander, Oscar P.B, additional, Görgens, André, additional, Conceição, Mariana, additional, Corso, Giulia, additional, Liang, Xiuming, additional, Seow, Yiqi, additional, Balsu, Sriram, additional, Felldin, Ulrika, additional, Bostancioglu, Beklem, additional, Fiona Lee, Yi Xin, additional, Hean, Justin, additional, Mäger, Imre, additional, Roberts, Thomas C., additional, Gustafsson, Manuela, additional, Mohammad, Dara K, additional, Sork, Helena, additional, Bäcklund, Alexandra, additional, Edvard Smith, C.I., additional, Wood, Matthew J.A., additional, Vandenbroucke, Roosmarijn, additional, Nordin, Joel Z., additional, and Andaloussi, Samir EL, additional

Published
2020
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22. Journal of Extracellular Vesicles / Systematic characterization of extracellular vesicle sorting domains and quantification at the single molecule single vesicle level by fluorescence correlation spectroscopy and single particle imaging

Author

Corso, Giulia, Heusermann, Wolf, Trojer, Dominic, Görgens, André, Steib, Emmanuelle, Voshol, Johannes, Graff, Alexandra, Genoud, Christel, Lee, Yi, Hean, Justin, Nordin, Joel Z., Wiklander, Oscar P.B., El Andaloussi, Samir, and Meisner-Kober, Nicole

Abstract

Extracellular vesicles (EV) convey biological information by transmitting macromolecules between cells and tissues and are of great promise as pharmaceutical nanocarriers, and as therapeutic per se. Strategies for customizing the EV surface and cargo are being developed to enable their tracking, visualization, loading with pharmaceutical agents and decoration of the surface with tissue targeting ligands. While much progress has been made in the engineering of EVs, an exhaustive comparative analysis of the most commonly exploited EV-associated proteins, as well as a quantification at the molecular level are lacking. Here, we selected 12 EV-related proteins based on MS-proteomics data for comparative quantification of their EV engineering potential. All proteins were expressed with fluorescent protein (FP) tags in EV-producing cells; both parent cells as well as the recovered vesicles were characterized biochemically and biophysically. Using Fluorescence Correlation Spectroscopy (FCS) we quantified the number of FP-tagged molecules per vesicle. We observed different loading efficiencies and specificities for the different proteins into EVs. For the candidates showing the highest loading efficiency in terms of engineering, the molecular levels in the vesicles did not exceed ca 4060 fluorescent proteins per vesicle upon transient overexpression in the cells. Some of the GFPtagged EV reporters showed quenched fluorescence and were either non-vesicular, despite copurification with EVs, or comprised a significant fraction of truncated GFP. The co-expression of each target protein with CD63 was further quantified by widefield and confocal imaging of single vesicles after double transfection of parent cells. In summary, we provide a quantitative comparison for the most commonly used sorting proteins for bioengineering of EVs and introduce a set of biophysical techniques for straightforward quantitative and qualitative characterization of fluorescent EVs to link single vesicle analysis with single molecule quantification. (VLID)4486110

Published
2019
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23. Purification, profiling and bioengineering of extracellular vesicles

Author

Corso, Giulia and Corso, Giulia

Abstract

The nano-sized membrane enclosed extracellular vesicles (EVs) transfer macromolecular information in the form of proteins, nucleic acids and lipids across cells. They are important mediators of cell-to-cell communication, but their relatively small size makes EV isolation and down-stream analysis challenging. In this thesis, we ventured through some of the current challenges in the EV field touching upon purification, small RNA and protein content profiling and ultimately characterization of engineered vesicles at the molecular level. The isolation of EVs from the complex fluid they are surrounded by, represents the first hindrance in studying these vesicles. Ideally, the purification method should preserve the integrity and natural properties of the EVs and simultaneously deplete the vesicular portion from unwanted components. In Paper I, we describe a novel liquid chromatography technique for EV purification, that combines size separation with bind elution (BE-SEC) entrapping molecules smaller than 700 kDa within the matrix core. The BE-SEC isolation method yields high particles recovery in a reproducible and time-efficient way, without neither affecting the EVs natural surface protein signature nor their physicochemical properties. By adding a prior tangential flow filtration step, the BE-SEC could be scaled-up and the EV preparation further depleted from unwanted non-vesicular proteins and RNAs. Secondly, therapeutically engineered EVs are promising delivery vehicles and linking the administered vesicular dose to the molecular cargo concentration is of extreme relevance to achieve a desired response. Therefore, analytical methods focused on single vesicles quantification rather than ‘bulk’ analysis and improved bioengineered vesicles are of utmost importance for therapeutic applications. In Paper II, we extensively characterize a set of fluorescently labelled EV-associated proteins, employing several qualitative and quantitative methods. Using Fluorescence Corre

Published
2019

24. Systematic characterization of extracellular vesicle sorting domains and quantification at the single molecule – single vesicle level by fluorescence correlation spectroscopy and single particle imaging

Author

Corso, Giulia, primary, Heusermann, Wolf, additional, Trojer, Dominic, additional, Görgens, André, additional, Steib, Emmanuelle, additional, Voshol, Johannes, additional, Graff, Alexandra, additional, Genoud, Christel, additional, Lee, Yi, additional, Hean, Justin, additional, Nordin, Joel Z., additional, Wiklander, Oscar P.B., additional, El Andaloussi, Samir, additional, and Meisner-Kober, Nicole, additional

Published
2019
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25. Systematic Methodological Evaluation of a Multiplex Bead-Based Flow Cytometry Assay for Detection of Extracellular Vesicle Surface Signatures

Author

Wiklander, Oscar P. B., primary, Bostancioglu, R. Beklem, additional, Welsh, Joshua A., additional, Zickler, Antje M., additional, Murke, Florian, additional, Corso, Giulia, additional, Felldin, Ulrika, additional, Hagey, Daniel W., additional, Evertsson, Björn, additional, Liang, Xiu-Ming, additional, Gustafsson, Manuela O., additional, Mohammad, Dara K., additional, Wiek, Constanze, additional, Hanenberg, Helmut, additional, Bremer, Michel, additional, Gupta, Dhanu, additional, Björnstedt, Mikael, additional, Giebel, Bernd, additional, Nordin, Joel Z., additional, Jones, Jennifer C., additional, EL Andaloussi, Samir, additional, and Görgens, André, additional

Published
2018
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28. Lipid-based Transfection Reagents Exhibit Cryo-induced Increase in Transfection Efficiency

Author

CDL Nanomedicine, Circulatory Health, CDL Staf Research, Sork, Helena, Nordin, Joel Z, Turunen, Janne J, Wiklander, Oscar Pb, Bestas, Burcu, Zaghloul, Eman M, Margus, Helerin, Padari, Kärt, Duru, Adil D, Corso, Giulia, Bost, Jeremy, Vader, Pieter, Pooga, Margus, Smith, Ci Edvard, Wood, Matthew Ja, Schiffelers, Raymond M, Hällbrink, Mattias, Andaloussi, Samir El, CDL Nanomedicine, Circulatory Health, CDL Staf Research, Sork, Helena, Nordin, Joel Z, Turunen, Janne J, Wiklander, Oscar Pb, Bestas, Burcu, Zaghloul, Eman M, Margus, Helerin, Padari, Kärt, Duru, Adil D, Corso, Giulia, Bost, Jeremy, Vader, Pieter, Pooga, Margus, Smith, Ci Edvard, Wood, Matthew Ja, Schiffelers, Raymond M, Hällbrink, Mattias, and Andaloussi, Samir El

Published
2016

29. Extracellular vesicle in vivo biodistribution is determined by cell source, route of administration and targeting

Author

Wiklander, Oscar P B, Nordin, Joel Z, O'Loughlin, Aisling, Gustafsson, Ylva, Corso, Giulia, Mäger, Imre, Vader, Pieter, Lee, Yi, Sork, Helena, Seow, Yiqi, Heldring, Nina, Alvarez-Erviti, Lydia, Smith, Ci Edvard, Le Blanc, Katarina, Macchiarini, Paolo, Jungebluth, Philipp, Wood, Matthew J A, Andaloussi, Samir El, Wiklander, Oscar P B, Nordin, Joel Z, O'Loughlin, Aisling, Gustafsson, Ylva, Corso, Giulia, Mäger, Imre, Vader, Pieter, Lee, Yi, Sork, Helena, Seow, Yiqi, Heldring, Nina, Alvarez-Erviti, Lydia, Smith, Ci Edvard, Le Blanc, Katarina, Macchiarini, Paolo, Jungebluth, Philipp, Wood, Matthew J A, and Andaloussi, Samir El

Published
2015

30. Extracellular vesicle in vivo biodistribution is determined by cell source, route of administration and targeting

Author

CDL Nanomedicine, Circulatory Health, Wiklander, Oscar P B, Nordin, Joel Z, O'Loughlin, Aisling, Gustafsson, Ylva, Corso, Giulia, Mäger, Imre, Vader, Pieter, Lee, Yi, Sork, Helena, Seow, Yiqi, Heldring, Nina, Alvarez-Erviti, Lydia, Smith, Ci Edvard, Le Blanc, Katarina, Macchiarini, Paolo, Jungebluth, Philipp, Wood, Matthew J A, Andaloussi, Samir El, CDL Nanomedicine, Circulatory Health, Wiklander, Oscar P B, Nordin, Joel Z, O'Loughlin, Aisling, Gustafsson, Ylva, Corso, Giulia, Mäger, Imre, Vader, Pieter, Lee, Yi, Sork, Helena, Seow, Yiqi, Heldring, Nina, Alvarez-Erviti, Lydia, Smith, Ci Edvard, Le Blanc, Katarina, Macchiarini, Paolo, Jungebluth, Philipp, Wood, Matthew J A, and Andaloussi, Samir El

Published
2015

31. Extracellular vesicle in vivo biodistribution is determined by cell source, route of administration and targeting

Author

Wiklander, Oscar P. B., primary, Nordin, Joel Z., additional, O'Loughlin, Aisling, additional, Gustafsson, Ylva, additional, Corso, Giulia, additional, Mäger, Imre, additional, Vader, Pieter, additional, Lee, Yi, additional, Sork, Helena, additional, Seow, Yiqi, additional, Heldring, Nina, additional, Alvarez‐Erviti, Lydia, additional, Smith, CI Edvard, additional, Le Blanc, Katarina, additional, Macchiarini, Paolo, additional, Jungebluth, Philipp, additional, Wood, Matthew J. A., additional, and Andaloussi, Samir EL, additional

Published
2015
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32. The exosome membrane localization of histones is independent of DNA and upregulated in response to stress

Author

Muthukrishnan, Uma, Natarajan, Balasubramanian, Mäger, Imre, Levén May, Hanna, Jones, Iwan, Corso, Giulia, Nordin, Joel Z., Wiklander, Oscar, Johansson, Henrik J., Lehtiö, Janne, Hällbrink, Mattias, Wood, Matthew J., Sandblad, Linda, Nagaev, Ivan, Baranov, Vladimir, Mincheva-Nilsson, Lucia, Rome, Sophie, Pini, Adrian, Andaloussi, Samir EL, Gilthorpe, Jonathan D., Muthukrishnan, Uma, Natarajan, Balasubramanian, Mäger, Imre, Levén May, Hanna, Jones, Iwan, Corso, Giulia, Nordin, Joel Z., Wiklander, Oscar, Johansson, Henrik J., Lehtiö, Janne, Hällbrink, Mattias, Wood, Matthew J., Sandblad, Linda, Nagaev, Ivan, Baranov, Vladimir, Mincheva-Nilsson, Lucia, Rome, Sophie, Pini, Adrian, Andaloussi, Samir EL, and Gilthorpe, Jonathan D.

Abstract

Extracellular histones contribute to many acute and chronic diseases but also populate the secretomes of healthy cells and biofluids. However, a secretory pathway for histones has not been described. Here we report that core and linker histones localize to multivesicular bodies and are secreted via exosomes. Histones are tightly associated with the exosome membrane, with N-terminal domains exposed, in a DNA-independent manner. Furthermore, rapid upregulation of exosomal histones occurs following heat stress, accompanied by enhanced vesicle secretion and a shift towards a population of smaller vesicles. Proteomic analyses identified the downregulation of endosomal sorting complex required for transport (ESCRT) complex as a possible mechanism underlying increased histone secretion.We show for the first time that membrane-associated histones are actively secreted from intact cells via the multivesicular body/exosomal pathway. We demonstrate a novel pathway for extracellular histone release that may have a role in both health and disease.

33. Tangential Flow Filtration with or Without Subsequent Bind-Elute Size Exclusion Chromatography for Purification of Extracellular Vesicles.

Author

Nordin JZ, Bostancioglu RB, Corso G, and El Andaloussi S

Subjects
Cell Line, Humans, Mesenchymal Stem Cells chemistry, Mesenchymal Stem Cells cytology, Cell Fractionation methods, Chromatography, Gel methods, Extracellular Vesicles chemistry, Filtration methods
Abstract

Extracellular vesicles (EVs) have gained increased attention over the last decade due to their potential as biomarkers and therapeutic entities. However, the characterization and development of EV research has been hampered by the lack of sufficiently effective purification methods. Several concerns have been raised toward the gold standard purification method ultracentrifugation, such as operator-dependent yields, crushing and aggregation of vesicles, poor scalability, and relative lack of purity. Here, we describe, in details, the use of an alternative purification technique: tangential flow filtration with or without subsequent bind-elute size exclusion chromatography that we have previously shown to be reproducible and scalable for purification of EVs.

Published
2019
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