{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T12:33:57Z","timestamp":1790253237915,"version":"4.1.0"},"reference-count":32,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,4,18]],"date-time":"2022-04-18T00:00:00Z","timestamp":1650240000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Korea Health Technology R&amp;D Project through the Korea Health Industry Development Institute","award":["HI14C3484"],"award-info":[{"award-number":["HI14C3484"]}]},{"name":"Medinno Inc","award":["PHX0203851"],"award-info":[{"award-number":["PHX0203851"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Severe intraventricular hemorrhage (IVH) remains a major cause of high mortality and morbidity in extremely preterm infants. Mesenchymal stem cell (MSC) transplantation is a possible therapeutic option, and development of therapeutics with enhanced efficacy is necessary. This study investigated whether thrombin preconditioning improves the therapeutic efficacy of human Wharton\u2019s jelly-derived MSC transplantation for severe neonatal IVH, using a rat model. Severe neonatal IVH was induced by injecting 150 \u03bcL blood into each lateral ventricle on postnatal day (P) 4 in Sprague-Dawley rats. After 2 days (P6), na\u00efve MSCs or thrombin-preconditioned MSCs (1 \u00d7 105\/10 \u03bcL) were transplanted intraventricularly. After behavioral tests, brain tissues and cerebrospinal fluid of P35 rats were obtained for histological and biochemical analyses, respectively. Thrombin-preconditioned MSC transplantation significantly reduced IVH-induced ventricular dilatation on in vivo magnetic resonance imaging, which was coincident with attenuations of reactive gliosis, cell death, and the number of activated microglia and levels of inflammatory cytokines after IVH induction, compared to na\u00efve MSC transplantation. In the behavioral tests, the sensorimotor and memory functions significantly improved after transplantation of thrombin-preconditioned MSCs, compared to na\u00efve MSCs. Overall, thrombin preconditioning significantly improves the therapeutic potential and more effectively attenuates brain injury, including progressive ventricular dilatation, gliosis, cell death, inflammation, and neurobehavioral functional impairment, in newborn rats with induced severe IVH than does na\u00efve MSC transplantation.<\/jats:p>","DOI":"10.3390\/ijms23084447","type":"journal-article","created":{"date-parts":[[2022,4,18]],"date-time":"2022-04-18T22:04:02Z","timestamp":1650319442000},"page":"4447","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Thrombin Preconditioning Improves the Therapeutic Efficacy of Mesenchymal Stem Cells in Severe Intraventricular Hemorrhage Induced Neonatal Rats"],"prefix":"10.3390","volume":"23","author":[{"given":"So Yeon","family":"Jung","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea"},{"name":"Department of Anatomy & Cell Biology, Sungkyunkwan University School of Medicine, Suwon 16419, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young Eun","family":"Kim","sequence":"additional","affiliation":[{"name":"Samsung Medical Center, Cell and Gene Therapy Institute, Seoul 06351, Korea"},{"name":"Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul 06351, 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 06351, Korea"},{"name":"Samsung Medical Center, Cell and Gene Therapy Institute, Seoul 06351, Korea"},{"name":"Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul 06351, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"So Yoon","family":"Ahn","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong Kyung","family":"Sung","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Se In","family":"Sung","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2750-405X","authenticated-orcid":false,"given":"Kyeung Min","family":"Joo","sequence":"additional","affiliation":[{"name":"Department of Anatomy & Cell Biology, Sungkyunkwan University School of Medicine, Suwon 16419, Korea"},{"name":"Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul 06351, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seong Gi","family":"Kim","sequence":"additional","affiliation":[{"name":"Center for Neuroscience Imaging Research (CNIR), Institute for Basic Science (IBS), Suwon 16419, Korea"},{"name":"Department of Biomedical Engineering, Sungkyunkwan University, Suwon 16419, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9201-2938","authenticated-orcid":false,"given":"Yun Sil","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea"},{"name":"Samsung Medical Center, Cell and Gene Therapy Institute, Seoul 06351, Korea"},{"name":"Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul 06351, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.clp.2013.09.007","article-title":"Pathogenesis and prevention of intraventricular hemorrhage","volume":"41","author":"Ballabh","year":"2014","journal-title":"Clin. 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