{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T22:10:36Z","timestamp":1792879836888,"version":"4.5.0"},"reference-count":60,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,5,6]],"date-time":"2022-05-06T00:00:00Z","timestamp":1651795200000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["2016\u201002854"],"award-info":[{"award-number":["2016\u201002854"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002794","name":"Cancerfonden","doi-asserted-by":"publisher","award":["CAN2017\/739"],"award-info":[{"award-number":["CAN2017\/739"]}],"id":[{"id":"10.13039\/501100002794","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003793","name":"Hj\u00e4rt-Lungfonden","doi-asserted-by":"publisher","award":["2018\u20100569"],"award-info":[{"award-number":["2018\u20100569"]}],"id":[{"id":"10.13039\/501100003793","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Extracellular Vesicle"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:bold>Background<\/jats:bold>\n                    : The ability to isolate extracellular vesicles (EVs) from blood is vital in the development of EVs as disease biomarkers. Both serum and plasma can be used, but few studies have compared these sources in terms of the type of EVs that are obtained. The aim of this study was to determine the presence of different subpopulations of EVs in plasma and serum.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Method<\/jats:bold>\n                    : Blood was collected from healthy subjects, and plasma and serum were isolated in parallel. ACD or EDTA tubes were used for the collection of plasma, while serum was obtained in clot activator tubes. EVs were isolated utilising a combination of density cushion and SEC, a combination of density cushion and gradient or by a bead antibody capturing system (anti\u2010CD63, anti\u2010CD9 and anti\u2010CD81 beads). The subpopulations of EVs were analysed by NTA, Western blot, SP\u2010IRIS, conventional and nano flow cytometry, magnetic bead ELISA and mass spectrometry. Additionally, different isolation protocols for plasma were compared to determine the contribution of residual platelets in the analysis.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results<\/jats:bold>\n                    : This study shows that a higher number of CD9\n                    <jats:sup>+<\/jats:sup>\n                    EVs were present in EDTA\u2010plasma compared to ACD\u2010plasma and to serum, and the presence of CD41a on these EVs suggests that they were released from platelets. Furthermore, only a very small number of EVs in blood were double\u2010positive for CD63 and CD81. The CD63\n                    <jats:sup>+<\/jats:sup>\n                    EVs were enriched in serum, while CD81\n                    <jats:sup>+<\/jats:sup>\n                    vesicles were the rarest subpopulation in both plasma and serum. Additionally, EDTA\u2010plasma contained more residual platelets than ACD\u2010plasma and serum, and two centrifugation steps were crucial to reduce the number of platelets in plasma prior to EV isolation.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusion<\/jats:bold>\n                    : These results show that human blood contains multiple subpopulations of EVs that carry different tetraspanins. Blood sampling methods, including the use of anti\u2010coagulants and choice of centrifugation protocols, can affect EV analyses and should always be reported in detail.\n                  <\/jats:p>","DOI":"10.1002\/jev2.12213","type":"journal-article","created":{"date-parts":[[2022,5,7]],"date-time":"2022-05-07T02:36:17Z","timestamp":1651890977000},"source":"Crossref","is-referenced-by-count":211,"title":["Tetraspanins distinguish separate extracellular vesicle subpopulations in human serum and plasma \u2013 Contributions of platelet extracellular vesicles in plasma samples"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1499-6876","authenticated-orcid":false,"given":"Nasibeh","family":"Karimi","sequence":"first","affiliation":[{"name":"Krefting Research Centre Department of Internal Medicine and Clinical Nutrition Institute of Medicine Sahlgrenska Academy University of Gothenburg  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Razieh","family":"Dalirfardouei","sequence":"additional","affiliation":[{"name":"Krefting Research Centre Department of Internal Medicine and Clinical Nutrition Institute of Medicine Sahlgrenska Academy University of Gothenburg  Gothenburg Sweden"},{"name":"Endometrium and Endometriosis Research Center Hamadan University of Medical Sciences  Hamadan Iran"},{"name":"Faculty of Medicine Department of Medical Biotechnology Mashhad University of Medical Sciences  Mashhad Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom\u00e1s","family":"Dias","sequence":"additional","affiliation":[{"name":"Mursla Ltd.  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"L\u00f6tvall","sequence":"additional","affiliation":[{"name":"Krefting Research Centre Department of Internal Medicine and Clinical Nutrition Institute of Medicine Sahlgrenska Academy University of Gothenburg  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1279-1746","authenticated-orcid":false,"given":"Cecilia","family":"L\u00e4sser","sequence":"additional","affiliation":[{"name":"Krefting Research Centre Department of Internal Medicine and Clinical Nutrition Institute of Medicine Sahlgrenska Academy University of Gothenburg  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,5,6]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-020-01402-3"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/20013078.2019.1596016"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2016.08.007"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.3402\/jev.v1i0.18397"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.3402\/jev.v3.23430"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/09537104.2016.1268255"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1026437522882"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1080\/20013078.2019.1647027"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4185"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.117.309417"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1080\/20013078.2020.1722433"},{"issue":"1","key":"e_1_2_7_13_1","first-page":"D1145","article-title":"The ProteomeXchange consortium in 2020: Enabling \u2018big data\u2019 approaches in proteomics","volume":"48","author":"Deutsch E. W.","year":"2020","journal-title":"Nucleic Acids Research"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1080\/20013078.2020.1736935"},{"key":"e_1_2_7_15_1","article-title":"An electro\u2010optical bead\u2010nanochip technology for the ultrasensitive and multi\u2010dimensional detection of small extracellular vesicles and their markers","author":"Dias T.","journal-title":"bioRxiv"},{"key":"e_1_2_7_16_1","doi-asserted-by":"crossref","unstructured":"Fordjour F. K. Daaboul G. G. &Gould S. J.(2019)A shared pathway of exosome biogenesis operates at plasma and endosome membranes. bioRxiv.https:\/\/doi.org\/10.1101\/545228","DOI":"10.1101\/545228"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.3402\/jev.v5.32945"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2013.11.010"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V94.11.3791"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkn923"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.211"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1080\/20013078.2019.1635420"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-018-2773-4"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/1479-5876-9-86"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.3402\/jev.v5.29975"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21155539"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1521230113"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2011.04610.x"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1517\/14712598.2015.977250"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/1479-5876-9-9"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.0c09873"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2012.11.039"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-7652-2_7"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1327.1999.00467.x"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V97.12.3755"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2016.00288"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-24384-2"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-021-00987-1"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2014.06.007"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0188921"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0236439"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1106"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20081126"},{"key":"e_1_2_7_44_1","first-page":"1","article-title":"Platelet removal by single\u2010step centrifugation","volume":"32","author":"Rikkert L. G.","year":"2020","journal-title":"Platelets"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.201800155"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.12669\/pjms.293.3497"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.117.311767"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1080\/20013078.2019.1582237"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2021.05.041"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1800"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-10360-4"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1080\/20013078.2018.1535750"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2016.0479"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2009.03613.x"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-019-0236-5"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1002\/adbi.201900310"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201703206"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V88.3.907.907"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.3402\/jev.v5.31209"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.3402\/jev.v2i0.20360"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-020-00258-9"}],"container-title":["Journal of Extracellular Vesicles"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jev2.12213","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jev2.12213","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/isevjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jev2.12213","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T16:30:16Z","timestamp":1760632216000},"score":1,"resource":{"primary":{"URL":"https:\/\/isevjournals.onlinelibrary.wiley.com\/doi\/10.1002\/jev2.12213"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5]]},"references-count":60,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2022,5]]}},"alternative-id":["10.1002\/jev2.12213"],"URL":"https:\/\/doi.org\/10.1002\/jev2.12213","archive":["Portico"],"relation":{},"ISSN":["2001-3078","2001-3078"],"issn-type":[{"value":"2001-3078","type":"print"},{"value":"2001-3078","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5]]},"article-number":"e12213"}}