MIBlood-EV: Minimal information to enhance the quality and reproducibility of blood extracellular vesicle research

Fabrice Lucien^{1

2}, Dakota Gustafson^{3

4

5}, Metka Lenassi⁶, Bo Li^{7

8}, Jacob J Teske¹, Eric Boilard⁹, Katharina Clemm von Hohenberg¹⁰, Juan Manual Falcón-Perez^{11

12}, Alice Gualerzi¹³, Antonia Reale¹⁴, Jennifer C Jones¹⁵, Cecilia Lässer¹⁶, Charlotte Lawson¹⁷, Irina Nazarenko^{18

19}, Lorraine O'Driscoll²⁰, Ryan Pink²¹, Pia R-M Siljander²², Carolina Soekmadji²³, An Hendrix²⁴, Joshua A Welsh²⁵, Kenneth W Witwer²⁵, Rienk Nieuwland⁸

Affiliations

¹ Department of Urology, Mayo Clinic, Rochester, Minnesota, USA.
² Department of Immunology, Mayo Clinic, Rochester, Minnesota, USA.
³ Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, Ontario, Canada.
⁴ Toronto General Hospital Research Institute, Toronto, Ontario, Canada.
⁵ Department of Public Health Sciences, Queen's University, Kingston, Ontario, Canada.
⁶ Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
⁷ Department of Laboratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China.
⁸ Laboratory of Experimental Clinical Chemistry, and Amsterdam Vesicle Center, Amsterdam UMC, location AMC, Amsterdam, Netherlands.
⁹ Centre de Recherche du CHU de Québec - Université Laval, Département de microbiologie et immunologie, Faculté de Médecine de l'Université Laval, Québec, Quebec, Canada.
¹⁰ Translational Lymphoma Research Group, German Cancer Research Center DKFZ, Heidelberg, Germany.
¹¹ Exosomes laboratory and Metabolomics Platform, CIC bioGUNE-BRTA, Derio, Spain.
¹² IKERBASQUE, Basque Foundation for Science, Bilbao, Spain.
¹³ IRCCS Fondazione Don Carlo Gnocchi, Milan, Italy.
¹⁴ Division of Blood Cancers, Monash University - Alfred Health, Melbourne, Victoria, Australia.
¹⁵ Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
¹⁶ Krefting Research Centre, Institute of Medicine at the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
¹⁷ Comparative Biomedical Sciences, Royal Veterinary College, London, UK.
¹⁸ Institute for Infection Prevention and Control, Faculty of Medicine, University of Freiburg, Freiburg, Germany, German Cancer Consortium.
¹⁹ Partner Site Freiburg and German Cancer Research Center, Heidelberg, Germany.
²⁰ School of Pharmacy and Pharmaceutical Sciences & Trinity Biomedical Sciences Institute & Trinity St. James's Cancer Institute, Trinity College Dublin, Dublin, Ireland.
²¹ Faculty Health and Life Sciences, Oxford Brookes University, Oxford, United Kingdom of Great Britain and Northern Ireland.
²² EV-group, Molecular and Integrative Biosciences Research Programme, Faculty of Biological and Environmental Sciences, and Drug Research Program, Faculty of Pharmacy, Division of Pharmaceutical Biosciences, University of Helsinki, Helsinki, Finland.
²³ School of Biomedical Sciences, Faculty of Medicine, University of Queensland, Brisbane, Australia.
²⁴ Laboratory of Experimental Cancer Research, Department of Human Structure and Repair, Ghent University, Ghent, Belgium.
²⁵ School of Medicine, Department of Molecular and Comparative Pathobiology, and Department of Neurology, Johns Hopkins University, Baltimore, Maryland, United States.

PMID: 38063210
PMCID: PMC10704543
DOI: 10.1002/jev2.12385

Meta-Analysis

MIBlood-EV: Minimal information to enhance the quality and reproducibility of blood extracellular vesicle research

Fabrice Lucien et al. J Extracell Vesicles. 2023 Dec.

. 2023 Dec;12(12):e12385.

doi: 10.1002/jev2.12385.

Authors

Affiliations

¹ Department of Urology, Mayo Clinic, Rochester, Minnesota, USA.
² Department of Immunology, Mayo Clinic, Rochester, Minnesota, USA.
³ Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, Ontario, Canada.
⁴ Toronto General Hospital Research Institute, Toronto, Ontario, Canada.
⁵ Department of Public Health Sciences, Queen's University, Kingston, Ontario, Canada.
⁶ Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
⁷ Department of Laboratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China.
⁸ Laboratory of Experimental Clinical Chemistry, and Amsterdam Vesicle Center, Amsterdam UMC, location AMC, Amsterdam, Netherlands.
⁹ Centre de Recherche du CHU de Québec - Université Laval, Département de microbiologie et immunologie, Faculté de Médecine de l'Université Laval, Québec, Quebec, Canada.
¹⁰ Translational Lymphoma Research Group, German Cancer Research Center DKFZ, Heidelberg, Germany.
¹¹ Exosomes laboratory and Metabolomics Platform, CIC bioGUNE-BRTA, Derio, Spain.
¹² IKERBASQUE, Basque Foundation for Science, Bilbao, Spain.
¹³ IRCCS Fondazione Don Carlo Gnocchi, Milan, Italy.
¹⁴ Division of Blood Cancers, Monash University - Alfred Health, Melbourne, Victoria, Australia.
¹⁵ Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
¹⁶ Krefting Research Centre, Institute of Medicine at the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
¹⁷ Comparative Biomedical Sciences, Royal Veterinary College, London, UK.
¹⁸ Institute for Infection Prevention and Control, Faculty of Medicine, University of Freiburg, Freiburg, Germany, German Cancer Consortium.
¹⁹ Partner Site Freiburg and German Cancer Research Center, Heidelberg, Germany.
²⁰ School of Pharmacy and Pharmaceutical Sciences & Trinity Biomedical Sciences Institute & Trinity St. James's Cancer Institute, Trinity College Dublin, Dublin, Ireland.
²¹ Faculty Health and Life Sciences, Oxford Brookes University, Oxford, United Kingdom of Great Britain and Northern Ireland.
²² EV-group, Molecular and Integrative Biosciences Research Programme, Faculty of Biological and Environmental Sciences, and Drug Research Program, Faculty of Pharmacy, Division of Pharmaceutical Biosciences, University of Helsinki, Helsinki, Finland.
²³ School of Biomedical Sciences, Faculty of Medicine, University of Queensland, Brisbane, Australia.
²⁴ Laboratory of Experimental Cancer Research, Department of Human Structure and Repair, Ghent University, Ghent, Belgium.
²⁵ School of Medicine, Department of Molecular and Comparative Pathobiology, and Department of Neurology, Johns Hopkins University, Baltimore, Maryland, United States.

PMID: 38063210
PMCID: PMC10704543
DOI: 10.1002/jev2.12385

Abstract

Blood is the most commonly used body fluid for extracellular vesicle (EV) research. The composition of a blood sample and its derivatives (i.e., plasma and serum) are not only donor-dependent but also influenced by collection and preparation protocols. Since there are hundreds of pre-analytical protocols and over forty variables, the development of standard operating procedures for EV research is very challenging. To improve the reproducibility of blood EV research, the International Society for Extracellular Vesicles (ISEV) Blood EV Task Force proposes standardized reporting of (i) the applied blood collection and preparation protocol and (ii) the quality of the prepared plasma and serum samples. Gathering detailed information will provide insight into the performance of the protocols and more effectively identify potential confounders in the prepared plasma and serum samples. To collect this information, the ISEV Blood EV Task Force created the Minimal Information for Blood EV research (MIBlood-EV), a tool to record and report information about pre-analytical protocols used for plasma and serum preparation as well as assays used to assess the quality of these preparations. This tool does not require modifications of established local pre-analytical protocols and can be easily implemented to enhance existing databases thereby enabling evidence-based optimization of pre-analytical protocols through meta-analysis. Taken together, insight into the quality of prepared plasma and serum samples will (i) improve the quality of biobanks for EV research, (ii) guide the exchange of plasma and serum samples between biobanks and laboratories, (iii) facilitate inter-laboratory comparative EV studies, and (iv) improve the peer review process.

Keywords: biomarker; blood; extracellular vesicles; liquid biopsy; quality control; reproducibility; standardization.

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Conflict of interest statement

J.C.J has collaborative research agreements with Beckman Coulter and Cytek Biosciences. R.P. received consulting fees from MetaGuideX. C.L. has collaborative research agreements with Astra Zeneca (Gothenburg, Sweden). E.B. received research funding from STRM Bio, Mitrix Bio, Veralox and Maresin Pharma. P.S. received funding support from the EV Ecosystem for Theranostic Platforms (Business Finland). K.W.W. has a collaborative research agreement with Ionis Pharmaceuticals; has served as an advisor to Exopharm, NeuroDex, Novadip, and ShiftBio; and performs ad hoc consulting on extracellular vesicles and RNA as Kenneth Witwer Consulting. All authors whose names are listed certify that they have no financial or non‐financial conflicts of interest that would have had influence on the subject matter and materials nor recommendations contained within this manuscript.

Figures

**FIGURE 1**
Proposed roadmap for MIBlood‐EV implementation and utilization.

See this image and copyright information in PMC

References

1. https://www.cdc.gov/ncezid/dvbd/stories/research‐lab‐diagnostics/hemolys...
1. Aatonen, M. T. , Ohman, T. , Nyman, T. A. , Laitinen, S. , Grönholm, M. , & Siljander, P. R. (2014). Isolation and characterization of platelet‐derived extracellular vesicles. Journal of extracellular vesicles, 3, 24692. - PMC - PubMed
1. Arce, J. E. , Welsh, J. A. , Cook, S. , Tigges, J. , Ghiran, I. , Jones, J. C. , Jackson, A. , Roth, M. , & Milosavljevic, A. (2023). The NanoFlow repository. Bioinformatics, 39, btad368. 10.1093/bioinformatics/btad368 - DOI - PMC - PubMed
1. Bekeris, L. G. , Tworek, J. A. , Walsh, M. K. , & Valenstein, P. N. (2005). Trends in blood culture contamination: A College of American Pathologists Q‐Tracks study of 356 institutions. Archives of Pathology & Laboratory Medicine, 129, 1222–1225. 10.5858/2005-129-1222-TIBCCA - DOI - PubMed
1. Bettin, B. , Gasecka, A. , Li, B. , Dhondt, B. , Hendrix, A. , Nieuwland, R. , & van der Pol, E. (2022). Removal of platelets from blood plasma to improve the quality of extracellular vesicle research. Journal of Thrombosis and Haemostasis, 20, 2679–2685. 10.1111/jth.15867 - DOI - PMC - PubMed

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MIBlood-EV: Minimal information to enhance the quality and reproducibility of blood extracellular vesicle research

Affiliations

MIBlood-EV: Minimal information to enhance the quality and reproducibility of blood extracellular vesicle research

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

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Full Text Sources