Liquid Biopsy in Organ Damage: small extracellular vesicle chip-based assessment of polytrauma

Bingduo Wang; Aliona Wöhler; Johannes Greven; Rebekka J S Salzmann; Cindy M Keller; Tobias Tertel; Qun Zhao; Ümit Mert; Klemens Horst; Ludmila Lupu; Markus Huber-Lang; Martijn van Griensven; Tom Erik Mollnes; Sebastian Schaaf; Robert Schwab; Christian P Strassburg; Ingo G H Schmidt-Wolf; Bernd Giebel; Frank Hildebrand; Veronika Lukacs-Kornek; Arnulf G Willms; Miroslaw T Kornek

doi:10.3389/fimmu.2023.1279496

Liquid Biopsy in Organ Damage: small extracellular vesicle chip-based assessment of polytrauma

Front Immunol. 2023 Nov 15:14:1279496. doi: 10.3389/fimmu.2023.1279496. eCollection 2023.

Authors

Bingduo Wang¹, Aliona Wöhler², Johannes Greven³, Rebekka J S Salzmann¹, Cindy M Keller¹, Tobias Tertel⁴, Qun Zhao³, Ümit Mert³, Klemens Horst³, Ludmila Lupu⁵, Markus Huber-Lang⁵, Martijn van Griensven⁶, Tom Erik Mollnes^{7

8

9}, Sebastian Schaaf², Robert Schwab², Christian P Strassburg¹, Ingo G H Schmidt-Wolf¹⁰, Bernd Giebel⁴, Frank Hildebrand³, Veronika Lukacs-Kornek^#¹¹, Arnulf G Willms^#^{11

12}, Miroslaw T Kornek^#^{1

2}

Affiliations

¹ Department of Internal Medicine I, University Hospital Bonn of the Rheinische Friedrich-Wilhelms-University, Bonn, Germany.
² Department of General, Visceral and Thoracic Surgery, German Armed Forces Central Hospital, Koblenz, Germany.
³ Department of Orthopaedics, Trauma and Reconstructive Surgery, University Hospital Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen, Aachen, Germany.
⁴ Institute for Transfusion Medicine, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
⁵ Institute of Clinical and Experimental Trauma Immunology, University Hospital Ulm, Ulm, Germany.
⁶ Department of Cell Biology-Inspired Tissue Engineering, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, Netherlands.
⁷ Research Laboratory, Nordland Hospital Bodø, Bodø, Norway.
⁸ Department of Immunology, Oslo University Hospital, and University of Oslo, Oslo, Norway.
⁹ Center of Molecular Inflammation Research, Norwegian University of Science and Technology, Trondheim, Norway.
¹⁰ Department of Integrated Oncology, Center for Integrated Oncology, University Hospital Bonn of the Rheinische Friedrich-Wilhelms-University, Bonn, Germany.
¹¹ Institute of Molecular Medicine and Experimental Immunology, University Hospital Bonn of the Rheinische Friedrich-Wilhelms-University, Bonn, Germany.
¹² Department of General and Visceral Surgery, German Armed Forces Hospital, Hamburg, Germany.

^# Contributed equally.

Abstract

Background: Despite major advances in medicine, blood-borne biomarkers are urgently needed to support decision-making, including polytrauma. Here, we assessed serum-derived extracellular vesicles (EVs) as potential markers of decision-making in polytrauma.

Objective: Our Liquid Biopsy in Organ Damage (LiBOD) study aimed to differentiate polytrauma with organ injury from polytrauma without organ injury. We analysed of blood-borne small EVs at the individual level using a combination of immunocapture and high-resolution imaging.

Methods: To this end, we isolated, purified, and characterized small EVs according to the latest Minimal Information for Studies of Extracellular Vesicles (MISEV) guidelines from human blood collected within 24 h post-trauma and validated our results using a porcine polytrauma model.

Results: We found that small EVs derived from monocytes CD14⁺ and CD14⁺CD61⁺ were significantly elevated in polytrauma with organ damage. To be precise, our findings revealed that CD9⁺CD14⁺ and CD14⁺CD61⁺ small EVs exhibited superior performance compared to CD9⁺CD61⁺ small EVs in accurately indicating polytrauma with organ damage, reaching a sensitivity and a specificity of 0.81% and 0.97%, respectively. The results in humans were confirmed in an independent porcine model of polytrauma.

Conclusion: These findings suggest that these specific types of small EVs may serve as valuable, non-invasive, and objective biomarkers for assessing and monitoring the severity of polytrauma and associated organ damage.

Keywords: biomarker; exosomes; extracellular vesicles; liquid biopsy; monocytes; trauma; triage.

Copyright © 2023 Wang, Wöhler, Greven, Salzmann, Keller, Tertel, Zhao, Mert, Horst, Lupu, Huber-Lang, van Griensven, Mollnes, Schaaf, Schwab, Strassburg, Schmidt-Wolf, Giebel, Hildebrand, Lukacs-Kornek, Willms and Kornek.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Biomarkers
Extracellular Vesicles* / pathology
Humans
Liquid Biopsy
Monocytes
Multiple Trauma* / pathology
Swine

Substances

Biomarkers

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. Studies were supported by the German Armed Forces (Bundeswehr, project number 31K1-S-10 2023) to AW, SS, RS, AGW, and MTK and the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) to MTK (DFG project number 410853455). VL-K is funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy (EXC 2151 – 390873048) and DFG Project numbers 411345524 and 432325352.