{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T09:51:11Z","timestamp":1790934671983,"version":"4.1.0"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2021,11,3]],"date-time":"2021-11-03T00:00:00Z","timestamp":1635897600000},"content-version":"vor","delay-in-days":323,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2020,12,15]],"date-time":"2020-12-15T00:00:00Z","timestamp":1607990400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2020,12,15]],"date-time":"2020-12-15T00:00:00Z","timestamp":1607990400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"name":"SMC-Ottogi Research Fund","award":["SMX1200831"],"award-info":[{"award-number":["SMX1200831"]}]},{"name":"ICT & Future Planning\/the Ministry of Education, Science and Technology","award":["2020R1A2C2010645"],"award-info":[{"award-number":["2020R1A2C2010645"]}]},{"name":"ICT & Future Planning\/the Ministry of Education, Science and Technology","award":["2017R1A2B2011383"],"award-info":[{"award-number":["2017R1A2B2011383"]}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministry of Health & Welfare, Republic of Korea","award":["HI14C3484"],"award-info":[{"award-number":["HI14C3484"]}]},{"DOI":"10.13039\/501100003710","name":"Korea Health Technology R&D Project through the Korea Health Industry Development Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Brain-derived neurotropic factor (BDNF), which is secreted by mesenchymal stem cells (MSCs), protects against severe intraventricular hemorrhage (IVH)-induced brain injuries. Although the paracrine protective effects of MSCs are mediated primarily by extracellular vesicles (EVs), the therapeutic efficacy of MSC-derived EVs and the role of the BDNF in the EVs have not been studied. This study aimed to determine whether MSC-derived EVs attenuate severe IVH-induced brain injuries, and if so, whether this protection is mediated by BDNF transfer. We compared the therapeutic efficacy of MSCs, MSC-derived EVs with or without BDNF knockdown, and fibroblast-derived EVs in vitro in rat cortical neuronal cells challenged with thrombin and in vivo in newborn rats by injecting 200\u2009\u03bcL of blood at postnatal day (P) 4 and transplanting 1\u2009\u00d7\u2009105 MSCs or 20\u2009\u03bcg of EVs at P6. The MSCs and MSC-derived EVs, but not the EVs derived from BDNF-knockdown MSCs or fibroblasts, significantly attenuated in vitro thrombin-induced neuronal cell death and in vivo severe IVH-induced brain injuries such as increased neuronal cell death, astrogliosis, and inflammatory responses; reduced myelin basic protein and neurogenesis; led to progression of posthemorrhagic hydrocephalus; and impaired behavioral test performance. Our data indicate that MSC-derived EVs are as effective as parental MSCs in attenuating severe IVH-induced brain injuries, and this neuroprotection is primarily mediated by BDNF transfer via EVs.<\/jats:p>","DOI":"10.1002\/sctm.20-0301","type":"journal-article","created":{"date-parts":[[2020,12,15]],"date-time":"2020-12-15T12:17:24Z","timestamp":1608034644000},"page":"374-384","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":74,"title":["Brain-derived neurotropic factor mediates neuroprotection of mesenchymal stem cell-derived extracellular vesicles against severe intraventricular hemorrhage in newborn rats"],"prefix":"10.1093","volume":"10","author":[{"given":"So Yoon","family":"Ahn","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Samsung Medical Center Sungkyunkwan University School of Medicine, Seoul, South Korea"},{"name":"Stem Cell and Regenerative Medicine Institute, Samsung Medical Center, Seoul, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong Kyung","family":"Sung","sequence":"additional","affiliation":[{"name":"Stem Cell and Regenerative Medicine Institute, Samsung Medical Center, Seoul, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young Eun","family":"Kim","sequence":"additional","affiliation":[{"name":"Stem Cell and Regenerative Medicine Institute, Samsung Medical Center, Seoul, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sein","family":"Sung","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Samsung Medical Center Sungkyunkwan University School of Medicine, Seoul, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun Sil","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Samsung Medical Center Sungkyunkwan University School of Medicine, Seoul, South Korea"},{"name":"Stem Cell and Regenerative Medicine Institute, Samsung Medical Center, Seoul, South Korea"},{"name":"Department of Health Sciences and Technology SAIHST, Sungkyunkwan University, Seoul, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Won Soon","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Samsung Medical Center Sungkyunkwan University School of Medicine, Seoul, South Korea"},{"name":"Stem Cell and Regenerative Medicine Institute, Samsung Medical Center, Seoul, South Korea"},{"name":"Department of Health Sciences and Technology SAIHST, Sungkyunkwan University, Seoul, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,12,15]]},"reference":[{"key":"2022022810502960000_sct312872-bib-0001","doi-asserted-by":"crossref","first-page":"251","DOI":"10.3345\/kjp.2014.57.6.251","article-title":"Mesenchymal stem cells transplantation for neuroprotection in preterm infants with severe intraventricular hemorrhage","volume":"57","author":"Ahn","year":"2014","journal-title":"Korean J Pediatr"},{"key":"2022022810502960000_sct312872-bib-0002","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/S0022-3476(78)80282-0","article-title":"Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm","volume":"92","author":"Papile","year":"1978","journal-title":"J Pediatr"},{"key":"2022022810502960000_sct312872-bib-0003","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1542\/peds.105.6.1216","article-title":"Neurodevelopmental and functional outcomes of extremely low birth weight infants in the National Institute of Child Health and Human Development Neonatal Research Network, 1993-1994","volume":"105","author":"Vohr","year":"2000","journal-title":"Pediatrics"},{"key":"2022022810502960000_sct312872-bib-0004","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/S0140-6736(97)12390-X","article-title":"International randomised controlled trial of acetazolamide and furosemide in posthaemorrhagic ventricular dilatation in infancy. 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