{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T18:41:07Z","timestamp":1771008067168,"version":"3.50.1"},"reference-count":42,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2019,5,20]],"date-time":"2019-05-20T00:00:00Z","timestamp":1558310400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Korea Health Technology R&amp;D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health &amp; Welfare, Republic of Korea","award":["HI16C1061"],"award-info":[{"award-number":["HI16C1061"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>We investigated whether thrombin preconditioning of human Wharton\u2019s jelly\u2013derived mesenchymal stem cells (MSCs) improves paracrine potency and thus the therapeutic efficacy of na\u00efve MSCs against severe hypoxic ischemic encephalopathy (HIE). Thrombin preconditioning significantly enhances the neuroprotective anti-oxidative, anti-apoptotic, and anti-cytotoxic effects of na\u00efve MSCs against oxygen\u2013glucose deprivation (OGD) of cortical neurons in vitro. Severe HIE was induced in vivo using unilateral carotid artery ligation and hypoxia for 2 h and confirmed using brain magnetic resonance imaging (MRI) involving &gt;40% of ipsilateral hemisphere at postnatal day (P) 7 in newborn rats. Delayed intraventricular transplantation of 1 \u00d7 105 thrombin preconditioned but not na\u00efve MSCs at 24 h after hypothermia significantly enhanced observed anti-inflammatory, anti-astroglial, and anti-apoptotic effects and the ensuing brain infarction; behavioral tests, such as cylinder rearing and negative geotaxis tests, were conducted at P42. In summary, thrombin preconditioning of human Wharton\u2019s jelly-derived MSCs significantly boosted the neuroprotective effects of na\u00efve MSCs against OGD in vitro by enhancing their anti-oxidative, anti-apoptotic, and anti-cytotoxic effects, and significantly attenuated the severe HIE-induced brain infarction and improved behavioral function tests in vivo by maximizing their paracrine anti-inflammatory, anti-astroglial, and anti-apoptotic effects.<\/jats:p>","DOI":"10.3390\/ijms20102477","type":"journal-article","created":{"date-parts":[[2019,5,20]],"date-time":"2019-05-20T11:05:07Z","timestamp":1558350307000},"page":"2477","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Thrombin Preconditioning Enhances Therapeutic Efficacy of Human Wharton\u2019s Jelly\u2013Derived Mesenchymal Stem Cells in Severe Neonatal Hypoxic Ischemic Encephalopathy"],"prefix":"10.3390","volume":"20","author":[{"given":"Young Eun","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Se In","family":"Sung","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yun Sil","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea"},{"name":"Stem Cell and Regenerative Medicine Institute, Samsung Medical Center, Seoul 06351, Korea"},{"name":"Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul 06351, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"So Yoon","family":"Ahn","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong Kyung","family":"Sung","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea"},{"name":"Stem Cell and Regenerative Medicine Institute, Samsung Medical Center, Seoul 06351, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Won Soon","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea"},{"name":"Stem Cell and Regenerative Medicine Institute, Samsung Medical Center, Seoul 06351, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,5,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/S0387-7604(96)00561-X","article-title":"Hypoxic and ischemic disorders of infants and children. 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