University of Oulu

Vergauwen, G., Tulkens, J., Pinheiro, C., Avila Cobos, F., Dedeyne, S., De Scheerder, M.-A., Vandekerckhove, L., Impens, F., Miinalainen, I., Braems, G., Gevaert, K., Mestdagh, P., Vandesompele, Jo, Denys, H., De Wever, O., & Hendrix, A. (2021). Robust sequential biophysical fractionation of blood plasma to study variations in the biomolecular landscape of systemically circulating extracellular vesicles across clinical conditions. Journal of Extracellular Vesicles, 10, e12122.

Robust sequential biophysical fractionation of blood plasma to study variations in the biomolecular landscape of systemically circulating extracellular vesicles across clinical conditions

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Author: Vergauwen, Glenn1,2,3; Tulkens, Joeri1,2; Pinheiro, Cláudio1,2;
Organizations: 1Department of Human Structure and Repair, Laboratory of Experimental Cancer Research, Ghent University, Ghent, Belgium
2Cancer Research Institute Ghent, Ghent, Belgium
3Department of Gynecology, Ghent University Hospital, Ghent, Belgium
4Department of Biomolecular Medicine, OncoRNALab, Ghent University, Ghent, Belgium
5Department of Internal Medicine and Pediatrics, HIV Cure Research Center, Ghent University Hospital, Ghent, Belgium
6VIB Center for Medical Biotechnology, Ghent, Belgium
7Department of Biomolecular Medicine, Ghent University, Ghent, Belgium
8VIB Proteomics Core, Ghent, Belgium
9Biocenter Oulu, University of Oulu, Oulu, Finland
10Department of Medical Oncology, Ghent University Hospital, Ghent, Belgium
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 9 MB)
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Language: English
Published: Informa, 2021
Publish Date: 2021-11-04


Separating extracellular vesicles (EV) from blood plasma is challenging and complicates their biological understanding and biomarker development. In this study, we fractionate blood plasma by combining size-exclusion chromatography (SEC) and OptiPrep density gradient centrifugation to study clinical context-dependent and time-dependent variations in the biomolecular landscape of systemically circulating EV. Using pooled blood plasma samples from breast cancer patients, we first demonstrate the technical repeatability of blood plasma fractionation. Using serial blood plasma samples from HIV and ovarian cancer patients (n = 10) we next show that EV carry a clinical context-dependent and/or time-dependent protein and small RNA composition, including miRNA and tRNA. In addition, differential analysis of blood plasma fractions provides a catalogue of putative proteins not associated with systemically circulating EV. In conclusion, the implementation of blood plasma fractionation allows to advance the biological understanding and biomarker development of systemically circulating EV.

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Series: Journal of extracellular vesicles
ISSN: 2001-3078
ISSN-E: 2001-3078
ISSN-L: 2001-3078
Volume: 10
Issue: 10
Article number: e12122
DOI: 10.1002/jev2.12122
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
Funding: This work was supported by Concerted Research Actions from Ghent University, the Fund for Scientific Spearheads of Ghent University Hospital, the National Cancer Plan, the Research Foundation-Flanders and Kom op tegen Kanker (Stand up to Cancer) and European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No [722148].
Copyright information: © 2021 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.