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dc.contributor.authorWelton, Joanne Louise
dc.contributor.authorLoveless, Samantha
dc.contributor.authorStone, Timothy
dc.contributor.authorvon Ruhland, Chris
dc.contributor.authorRobertson, Neil
dc.contributor.authorClayton, Aled
dc.date.accessioned2018-02-26T14:50:50Z
dc.date.available2018-02-26T14:50:50Z
dc.date.issued2017-09-03
dc.identifier.citationWelton, J.L., Loveless, S., Stone, T., von Ruhland, C., Robertson, N.P. and Clayton, A. (2017) 'Cerebrospinal fluid extracellular vesicle enrichment for protein biomarker discovery in neurological disease; multiple sclerosis', Journal of Extracellular Vesicles, 6(1), p.1369805.en_US
dc.identifier.issn2001-3078
dc.identifier.urihttp://hdl.handle.net/10369/9303
dc.descriptionThis short communication was published in Journal of Extracellular Vesicles on 03 September 2017 available open access at https://doi.org/10.1080/20013078.2017.1369805en_US
dc.description.abstractThe discovery of disease biomarkers, along with the use of “liquid biopsies” as a minimally invasive source of biomarkers, continues to be of great interest. In inflammatory diseases of the central nervous system (CNS), cerebrospinal fluid (CSF) is the most obvious biofluid source. Extracellular vesicles (EVs) are also present in CSF and are thought to be potential “biomarker treasure chests”. However, isolating these CSF-derived EVs remains challenging. This small-scale pilot study developed and tested a protocol to enrich for CSF-EVs, both in relapsing remitting multiple sclerosis (RRMS) CSF and controls. These were subsequently compared, using an aptamer based proteomics array, SOMAscan™. EVs were enriched from RRMS patient (n = 4) and non-demyelinating control (idiopathic intracranial hypertension (IIH) (n = 3)) CSF using precipitation and mini size-exclusion chromatography (SEC). EV-enriched fractions were selected using pre-defined EV characteristics, including increased levels of tetraspanins. EVs and paired CSF were analysed by SOMAscan™, providing relative abundance data for 1128 proteins. CSF-EVs were characterised, revealing exosome-like features: rich in tetraspanins CD9 and CD81, size ~100 nm, and exosome-like morphology by TEM. Sufficient quantities of, SOMAscan™ compatible, EV material was obtained from 5 ml CSF for proteomics analysis. Overall, 348 and 580 proteins were identified in CSF-EVs and CSF, respectively, of which 50 were found to be significantly (t-test) and exclusively enriched in RRMS CSF-EVs. Selected proteins, Plasma kallikrein and Apolipoprotein-E4, were further validated by western blot and appeared increased in CSF-EVs compared to CSF. Functional enrichment analysis of the 50 enriched proteins revealed strong associations with biological processes relating to MS pathology and also extracellular regions, consistent with EV enrichment. This pilot study demonstrates practicality for EV enrichment in CSF derived from patients with MS and controls, allowing detailed analysis of protein profiles that may offer opportunities to identify novel biomarkers and therapeutic approaches in CNS inflammatory diseasesen_US
dc.description.sponsorshipMultiple Sclerosis Society [Grant reference 13].en_US
dc.language.isoenen_US
dc.publisherTaylor & Francisen_US
dc.relation.ispartofseriesJournal of Extracellular Vesicles;
dc.subjectextracellular vesiclesen_US
dc.subjectmultiple sclerosisen_US
dc.subjectcerebrospinal fluiden_US
dc.subjectsize exclusion chromatographyen_US
dc.subjectproteomicsen_US
dc.subjectbiomarkersen_US
dc.titleCerebrospinal fluid extracellular vesicle enrichment for protein biomarker discovery in neurological disease; multiple sclerosisen_US
dc.typeArticleen_US
dc.identifier.doihttps://doi.org/10.1080/20013078.2017.1369805
dcterms.dateAccepted2017-08-15
rioxxterms.funderCardiff Metropolitan Universityen_US
rioxxterms.identifier.projectCardiff Metropolian (Internal)en_US
rioxxterms.versionVoRen_US
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by-nc/3.0/en_US
rioxxterms.licenseref.startdate2018-02-26
rioxxterms.funder.project37baf166-7129-4cd4-b6a1-507454d1372een_US


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