Recommendations for reproducibility of cerebrospinal fluid extracellular vesicle studies

Sandau, Ursula S.; Magaña, Setty M.; Costa, Júlia; Nolan, John P.; Ikezu, Tsuneya; Vella, Laura J.; Jackson, Hannah K.; Moreira, Lissette Retana; Palacio, Paola Loreto; Hill, Andrew F.; Quinn, Joseph F.; Van Keuren‐Jensen, Kendall R.; McFarland, Trevor J.; Palade, Joanna; Sribnick, Eric A.; Su, Huaqi; Vekrellis, Kostas; Coyle, Beth; Yang, You; Falcón‐Perez, Juan M.; Nieuwland, Rienk; Saugstad, Julie A.

Abstract

Cerebrospinal fluid (CSF) is a clear, transparent fluid derived from blood plasma that protects the brain and spinal cord against mechanical shock, provides buoyancy, clears metabolic waste and transports extracellular components to remote sites in the brain. Given its contact with the brain and the spinal cord, CSF is the most informative biofluid for studies of the central nervous system (CNS). In addition to other components, CSF contains extracellular vesicles (EVs) that carry bioactive cargoes (e.g., lipids, nucleic acids, proteins), and that can have biological functions within and beyond the CNS. Thus, CSF EVs likely serve as both mediators of and contributors to communication in the CNS. Accordingly, their potential as biomarkers for CNS diseases has stimulated much excitement for and attention to CSF EV research. However, studies on CSF EVs present unique challenges relative to EV studies in other biofluids, including the invasive nature of CSF collection, limited CSF volumes and the low numbers of EVs in CSF as compared to plasma. Here, the objectives of the International Society for Extracellular Vesicles CSF Task Force are to promote the reproducibility of CSF EV studies by providing current reporting and best practices, and recommendations and reporting guidelines, for CSF EV studies. To accomplish this, we created and distributed a world‐wide survey to ISEV members to assess methods considered ‘best practices’ for CSF EVs, then performed a detailed literature review for CSF EV publications that was used to curate methods and resources. Based on responses to the survey and curated information from publications, the CSF Task Force herein provides recommendations and reporting guidelines to promote the reproducibility of CSF EV studies in seven domains: (i) CSF Collection, Processing, and Storage; (ii) CSF EV Separation/Concentration; (iii) CSF EV Size and Number Measurements; (iv) CSF EV Protein Studies; (v) CSF EV RNA Studies; (vi) CSF EV Omics Studies and (vii) CSF EV Functional Studies.

Citation

Sandau, U. S., Magaña, S. M., Costa, J., Nolan, J. P., Ikezu, T., Vella, L. J., …International Society for Extracellular Vesicles Cerebrospinal Fluid Task Force. (2024). Recommendations for reproducibility of cerebrospinal fluid extracellular vesicle studies. Journal of Extracellular Vesicles, 13(1), Article 12397. https://doi.org/10.1002/jev2.12397

• Journal Article Type: Article
• Acceptance Date: Nov 21, 2023
• Online Publication Date: Dec 29, 2023
• Publication Date: 2024-01
• Deposit Date: Feb 7, 2024
• Publicly Available Date: Feb 7, 2024
• Journal: Journal of Extracellular Vesicles
• Electronic ISSN: 2001-3078
• Publisher: Taylor & Francis Open Access
• Peer Reviewed: Peer Reviewed
• Volume: 13
• Issue: 1
• Article Number: 12397
• DOI: https://doi.org/10.1002/jev2.12397
• Keywords: cerebrospinal fluid, biomarkers, recommendations and reporting, central nervous system, brain, exosome, extracellular vesicle
• Public URL: https://nottingham-repository.worktribe.com/output/29257260
• Publisher URL: https://isevjournals.onlinelibrary.wiley.com/doi/10.1002/jev2.12397