{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T06:31:58Z","timestamp":1781245918880,"version":"3.54.1"},"reference-count":62,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,4,28]],"date-time":"2020-04-28T00:00:00Z","timestamp":1588032000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003074","name":"Agencia Nacional de Promoci\u00f3n Cient\u00edfica y Tecnol\u00f3gica","doi-asserted-by":"publisher","award":["PICT 01798\u20102018"],"award-info":[{"award-number":["PICT 01798\u20102018"]}],"id":[{"id":"10.13039\/501100003074","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Previous work by our group has shown the pro\u2010differentiating effects of apotransferrin (aTf) on oligodendroglial cells in vivo and in vitro. Further studies showed the remyelinating effect of aTf in animal demyelination models such as hypoxia\/ischemia, where the intranasal administration of human aTf provided brain neuroprotection and reduced white matter damage, neuronal loss, and astrogliosis in different brain regions. These data led us to search for a less invasive and controlled technique to deliver aTf to the CNS. To such end, we isolated extracellular vesicles (EVs) from human and mouse plasma and different neuron and glia conditioned media and characterized them based on their quality, quantity, identity, and structural integrity by western blot, dynamic light scattering, and scanning electron microscopy. All sources yielded highly pure vesicles whose size and structures were in keeping with previous literary evidence. Given that, remarkably, EVs from all sources analyzed contained Tf receptor 1 (TfR1) in their composition, we employed two passive cargo\u2010loading strategies which rendered successful EV loading with aTf, specifically through binding to TfR1. These results unveil EVs as potential nanovehicles of aTf to be delivered into the CNS parenchyma, and pave the way for further studies into their possible clinical application in the treatment of demyelinating diseases.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc15019-fig-0006-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.15019","type":"journal-article","created":{"date-parts":[[2020,4,5]],"date-time":"2020-04-05T08:06:07Z","timestamp":1586073967000},"page":"327-338","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Extracellular vesicles containing the transferrin receptor as nanocarriers of apotransferrin"],"prefix":"10.1111","volume":"155","author":[{"given":"Vanesa S.","family":"Mattera","sequence":"first","affiliation":[{"name":"CONICET. Instituto de Qu\u00edmica y Fisicoqu\u00edmica Biol\u00f3gicas (IQUIFIB) Universidad de Buenos Aires Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pehu\u00e9n","family":"Pereyra Gerber","sequence":"additional","affiliation":[{"name":"Facultad de Farmacia y Bioqu\u00edmica Departamento de Qu\u00edmica Biol\u00f3gica. Buenos Aires Universidad de Buenos Aires Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romina","family":"Glisoni","sequence":"additional","affiliation":[{"name":"Facultad de Farmacia y Bioqu\u00edmica Departamento de Tecnolog\u00eda Farmac\u00e9utica Universidad de Buenos Aires Buenos Aires Argentina"},{"name":"Instituto de Nanobiotecnolog\u00eda (NANOBIOTEC) Universidad de Buenos Aires. CONICET Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matias","family":"Ostrowski","sequence":"additional","affiliation":[{"name":"Facultad de Farmacia y Bioqu\u00edmica Departamento de Qu\u00edmica Biol\u00f3gica. Buenos Aires Universidad de Buenos Aires Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra V.","family":"Verstraeten","sequence":"additional","affiliation":[{"name":"CONICET. Instituto de Qu\u00edmica y Fisicoqu\u00edmica Biol\u00f3gicas (IQUIFIB) Universidad de Buenos Aires Buenos Aires Argentina"},{"name":"Instituto de Investigaciones Biom\u00e9dicas en Retrovirus y SIDA Universidad de Buenos Aires. CONICET Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7683-0228","authenticated-orcid":false,"given":"Juana M.","family":"Pasquini","sequence":"additional","affiliation":[{"name":"CONICET. Instituto de Qu\u00edmica y Fisicoqu\u00edmica Biol\u00f3gicas (IQUIFIB) Universidad de Buenos Aires Buenos Aires Argentina"},{"name":"Instituto de Investigaciones Biom\u00e9dicas en Retrovirus y SIDA Universidad de Buenos Aires. CONICET Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge D.","family":"Correale","sequence":"additional","affiliation":[{"name":"FLENI Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,4,28]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2005.12.027"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-009-0051-1"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-014-9054-5"},{"issue":"2663","key":"e_1_2_8_5_1","first-page":"23","article-title":"Effect of transferrin on hypomyelination induced by iron deficiency","volume":"86","author":"Badaracco M. E.","year":"2008","journal-title":"Journal of Neuroscience Research"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2016.00127"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.carbpol.2019.115610"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.3402\/jev.v3.23430"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxh267"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20020434"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.RA118.000644"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejcb.2009.02.001"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.490210210"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2012.131"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1159\/000112116"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4547(19970315)47:6<603::AID-JNR5>3.0.CO;2-H"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22374"},{"key":"e_1_2_8_18_1","first-page":"e00048","article-title":"Apotransferrin\u2010induced recovery after hypoxic\/ischaemic injury on myelination","volume":"19","author":"Guardia Clausi M.","year":"2010","journal-title":"ASN Neurochemistry"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-09-307595"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2015.03.033"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.97.2.329"},{"key":"e_1_2_8_22_1","article-title":"Endocytosis and intracellular processing of transferrin and colloidal gold\u2010transferrin in rat reticulocytes: Demonstration of a pathway for receptor shedding","volume":"35","author":"Harding C.","year":"1984","journal-title":"European Journal of Cell Biology"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep36331"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.3402\/jev.v5.29289"},{"key":"e_1_2_8_25_1","doi-asserted-by":"crossref","unstructured":"Keri K. C. Regner K. R. Dall A. T. &Park F.(2018).Urinary exosomal expression of activator of G protein signaling 3 in polycystic kidney disease. BMC Research Notes 11:359.19.","DOI":"10.1186\/s13104-018-3467-6"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1521230113"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biotechadv.2012.08.008"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0005219"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1703920114"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2017.12"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0075054"},{"key":"e_1_2_8_32_1","first-page":"529","article-title":"Oligodendroglial cell differentiation in rat brain is accelerated by the intracranial injection of apotransferrin","volume":"46","author":"Marta C. B.","year":"2000","journal-title":"Molecular and Cellular Biology"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-018-0250-9"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.85.3.890"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.12.1.575"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.2165\/00126839-200708030-00001"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1159\/000064945"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(83)90040-5"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.101.3.942"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M900381-MCP200"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2013.06.014"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3258-14.2014"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4547(19960715)45:2<161::AID-JNR8>3.0.CO;2-8"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.22348"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2017.07.001"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-28748-5"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0033937"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1800"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.plipres.2017.03.001"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0198820"},{"issue":"146","key":"e_1_2_8_51_1","first-page":"25","article-title":"Characterisation of exosomes derived from human cells by nanoparticle tracking analysis and scanning electron microscopy","volume":"8","author":"Sokolova V.","year":"2011","journal-title":"Colloids and Surfaces B: Biointerfaces"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2012.06.014"},{"key":"e_1_2_8_53_1","first-page":"13","article-title":"MicroRNA signatures of tumor\u2010derived exosomes as diagnostic biomarkers of ovarian cancer","volume":"110","author":"Taylor D. D.","year":"2008","journal-title":"GynecolOncol."},{"issue":"3","key":"e_1_2_8_54_1","first-page":"1","article-title":"Isolation and characterization of exosomes from cell culture supernatants and biological fluids","volume":"30","author":"Th\u00e9ry C.","year":"2006","journal-title":"Current Protocols in Cell Biology"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200140120-00003"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1596"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.112.005983"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1993.tb03188.x"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20101825"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M207550200"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2011.98"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.8.118"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2011.164"}],"container-title":["Journal of Neurochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjnc.15019","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jnc.15019","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jnc.15019","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jnc.15019","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T19:40:54Z","timestamp":1693856454000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jnc.15019"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,28]]},"references-count":62,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2020,11]]}},"alternative-id":["10.1111\/jnc.15019"],"URL":"https:\/\/doi.org\/10.1111\/jnc.15019","archive":["Portico"],"relation":{},"ISSN":["0022-3042","1471-4159"],"issn-type":[{"value":"0022-3042","type":"print"},{"value":"1471-4159","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,28]]},"assertion":[{"value":"2019-10-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-03-25","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-04-28","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}