{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T19:16:27Z","timestamp":1791400587138,"version":"4.3.3"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2021,12,7]],"date-time":"2021-12-07T00:00:00Z","timestamp":1638835200000},"content-version":"vor","delay-in-days":1204,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Samsung Medical Center","award":["GFO2170091"],"award-info":[{"award-number":["GFO2170091"]}]},{"name":"Korean Healthcare Technology R&D Project, Ministry for Health, Welfare and Family Affairs, Republic of Korea","award":["HR14C0008"],"award-info":[{"award-number":["HR14C0008"]}]},{"name":"Korean Healthcare Technology R&D Project, Ministry for Health, Welfare and Family Affairs, Republic of Korea","award":["HI14C1596"],"award-info":[{"award-number":["HI14C1596"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>We previously demonstrated that transplanting mesenchymal stem cells (MSCs) improved recovery from brain injury induced by severe intraventricular hemorrhage (IVH) in newborn rats. To assess the safety and feasibility of MSCs in preterm infants with severe IVH, we performed a phase I dose-escalation clinical trial. The first three patients received a low dose of MSCs (5 \u00d7 106 cells\/kg), and the next six received a high dose (1 \u00d7 107 cells\/kg). We assessed adverse outcomes, including mortality and the progress of posthemorrhagic hydrocephalus. Intraventricular transplantation of MSCs was performed in nine premature infants with mean gestational age of 26.1 \u00b1 0.7 weeks and birth weight of 808 \u00b1 85 g at 11.6 \u00b1 0.9 postnatal days. Treatment with MSCs was well tolerated, and no patients showed serious adverse effects or dose-limiting toxicities attributable to MSC transplantation. There was no mortality in IVH patients receiving MSCs. Infants who underwent shunt surgery showed a higher level of interleukin (IL)-6 in cerebrospinal fluid (CSF) obtained before MSC transplantation in comparison with infants who did not receive a shunt. Levels of IL-6 and tumor necrosis factor-\u03b1 in initially obtained CSF correlated significantly with baseline ventricular index. Intraventricular transplantation of allogeneic human UCB-derived MSCs into preterm infants with severe IVH is safe and feasible, and warrants a larger, and controlled, phase II study.<\/jats:p>","DOI":"10.1002\/sctm.17-0219","type":"journal-article","created":{"date-parts":[[2018,8,22]],"date-time":"2018-08-22T16:17:30Z","timestamp":1534954650000},"page":"847-856","source":"Crossref","is-referenced-by-count":151,"title":["Mesenchymal Stem Cells for Severe Intraventricular Hemorrhage in Preterm Infants: Phase I Dose-Escalation Clinical Trial"],"prefix":"10.1093","volume":"7","author":[{"given":"So Yoon","family":"Ahn","sequence":"first","affiliation":[{"name":"a Department of Pediatrics, Samsung Medical Center Sungkyunkwan University School of Medicine, Seoul, South Korea"},{"name":"b Stem Cell and Regenerative Medicine Institute Samsung Medical Center, Seoul, South Korea"},{"name":"c Department of Health Sciences and Technology SAIHST, Sungkyunkwan University, Seoul, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun Sil","family":"Chang","sequence":"additional","affiliation":[{"name":"a Department of Pediatrics, Samsung Medical Center Sungkyunkwan University School of Medicine, Seoul, South Korea"},{"name":"b Stem Cell and Regenerative Medicine Institute Samsung Medical Center, Seoul, South Korea"},{"name":"c Department of Health Sciences and Technology SAIHST, Sungkyunkwan University, Seoul, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Se In","family":"Sung","sequence":"additional","affiliation":[{"name":"a Department of Pediatrics, Samsung Medical Center Sungkyunkwan University School of Medicine, Seoul, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Won Soon","family":"Park","sequence":"additional","affiliation":[{"name":"a Department of Pediatrics, Samsung Medical Center Sungkyunkwan University School of Medicine, Seoul, South Korea"},{"name":"b Stem Cell and Regenerative Medicine Institute Samsung Medical Center, Seoul, South Korea"},{"name":"c Department of Health Sciences and Technology SAIHST, Sungkyunkwan University, Seoul, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,8,21]]},"reference":[{"key":"2022022809090132200_sct312351-bib-0001","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1067\/mob.2001.117355","article-title":"Perinatal factors associated with severe intracranial hemorrhage","volume":"185","author":"Thorp","year":"2001","journal-title":"Am J Obstet Gynecol"},{"key":"2022022809090132200_sct312351-bib-0002","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1001\/jamapediatrics.2013.866","article-title":"Neurodevelopmental outcomes of extremely low-gestational-age neonates with low-grade periventricular-intraventricular hemorrhage","volume":"167","author":"Payne","year":"2013","journal-title":"JAMA Pediatr"},{"key":"2022022809090132200_sct312351-bib-0003","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1038\/pr.2017.46","article-title":"Neonatal outcomes of moderately preterm infants compared to extremely preterm infants","volume":"82","author":"Walsh","year":"2017","journal-title":"Pediatr Res"},{"key":"2022022809090132200_sct312351-bib-0004","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1542\/peds.2009-2959","article-title":"Neonatal outcomes of extremely preterm infants from the NICHD neonatal research network","volume":"126","author":"Stoll","year":"2010","journal-title":"Pediatrics"},{"key":"2022022809090132200_sct312351-bib-0005","doi-asserted-by":"crossref","first-page":"F37","DOI":"10.1136\/fn.87.1.F37","article-title":"Posthaemorrhagic ventricular dilatation in the premature infant: Natural history and predictors of outcome","volume":"87","author":"Murphy","year":"2002","journal-title":"Arch Dis Child Fetal Neonatal Ed"},{"key":"2022022809090132200_sct312351-bib-0006","article-title":"Treatment thresholds for intervention in posthaemorrhagic ventricular dilation: A randomised controlled trial","author":"Vries","year":"2018","journal-title":"Arch Dis Child Fetal Neonatal Ed"},{"key":"2022022809090132200_sct312351-bib-0007","doi-asserted-by":"crossref","first-page":"e0132919","DOI":"10.1371\/journal.pone.0132919","article-title":"Optimal route for mesenchymal stem cells transplantation after severe intraventricular hemorrhage in newborn rats","volume":"10","author":"Ahn","year":"2015","journal-title":"PLoS One"},{"key":"2022022809090132200_sct312351-bib-0008","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","volume":"352","author":"International PHVD Drug Trial Group","year":"1998","journal-title":"Lancet"},{"key":"2022022809090132200_sct312351-bib-0009","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1542\/peds.108.3.597","article-title":"Randomized, controlled trial of acetazolamide and furosemide in posthemorrhagic ventricular dilation in infancy: Follow-up at 1 year","volume":"108","author":"Kennedy","year":"2001","journal-title":"Pediatrics"},{"key":"2022022809090132200_sct312351-bib-0010","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1017\/S0012162299001644","article-title":"Relation of cranial ultrasound abnormalities in low-birthweight infants to motor or cognitive performance at ages 2, 6, and 9 years","volume":"41","author":"Pinto-Martin","year":"1999","journal-title":"Dev Med Child Neurol"},{"key":"2022022809090132200_sct312351-bib-0011","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1016\/j.jcyt.2015.03.008","article-title":"Cell type-dependent variation in paracrine potency determines therapeutic efficacy against neonatal hyperoxic lung injury","volume":"17","author":"Ahn","year":"2015","journal-title":"Cytotherapy"},{"key":"2022022809090132200_sct312351-bib-0012","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.3727\/096368911X565038a","article-title":"Intratracheal transplantation of human umbilical cord blood-derived mesenchymal stem cells dose-dependently attenuates hyperoxia-induced lung injury in neonatal rats","volume":"20","author":"Chang","year":"2011","journal-title":"Cell Transplant"},{"key":"2022022809090132200_sct312351-bib-0013","doi-asserted-by":"crossref","first-page":"869","DOI":"10.3727\/096368909X471189","article-title":"Human umbilical cord blood-derived mesenchymal stem cells attenuate hyperoxia-induced lung injury in neonatal rats","volume":"18","author":"Chang","year":"2009","journal-title":"Cell Transplant"},{"key":"2022022809090132200_sct312351-bib-0014","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1165\/rcmb.2013-0385OC","article-title":"Critical role of VEGF secreted by mesenchymal stem cells in hyperoxic lung injury","volume":"51","author":"Chang","year":"2014","journal-title":"Am J Respir Cell Mol Biol"},{"key":"2022022809090132200_sct312351-bib-0015","doi-asserted-by":"crossref","first-page":"e0120893","DOI":"10.1371\/journal.pone.0120893","article-title":"Hypothermia augments neuroprotective activity of mesenchymal stem cells for neonatal hypoxic-ischemic encephalopathy","volume":"10","author":"Park","year":"2015","journal-title":"PLoS One"},{"key":"2022022809090132200_sct312351-bib-0016","doi-asserted-by":"crossref","first-page":"1846","DOI":"10.1056\/NEJM200006223422501","article-title":"Graft-versus-host disease in children who have received a cord-blood or bone marrow transplant from an HLA-identical sibling. Eurocord and International Bone Marrow Transplant Registry Working Committee on Alternative Donor and Stem Cell Sources","volume":"342","author":"Rocha","year":"2000","journal-title":"N Engl J Med"},{"key":"2022022809090132200_sct312351-bib-0017","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1080\/14653240410005041","article-title":"Mesenchymal stem\/progenitor cells developed in cultures from UC blood","volume":"6","author":"Yang","year":"2004","journal-title":"Cytotherapy"},{"key":"2022022809090132200_sct312351-bib-0018","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1634\/stemcells.2005-0342","article-title":"Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue","volume":"24","author":"Kern","year":"2006","journal-title":"Stem Cells"},{"key":"2022022809090132200_sct312351-bib-0019","doi-asserted-by":"crossref","first-page":"17986","DOI":"10.3390\/ijms140917986","article-title":"Comparative analysis of human mesenchymal stem cells from bone marrow, adipose tissue, and umbilical cord blood as sources of cell therapy","volume":"14","author":"Jin","year":"2013","journal-title":"Int J Mol Sci"},{"issue":"1","key":"2022022809090132200_sct312351-bib-0020","doi-asserted-by":"crossref","first-page":"145","DOI":"10.3727\/096368916X692861","article-title":"Pivotal role of brain derived neurotrophic factor secreted by mesenchymal stem cells in severe intraventricular hemorrhage in the newborn rats","volume":"26","author":"Ahn","year":"2016","journal-title":"Cell Transplant"},{"key":"2022022809090132200_sct312351-bib-0021","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1161\/STROKEAHA.112.679092","article-title":"Mesenchymal stem cells prevent hydrocephalus after severe intraventricular hemorrhage","volume":"44","author":"Ahn","year":"2013","journal-title":"Stroke"},{"key":"2022022809090132200_sct312351-bib-0022","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1016\/j.jpeds.2013.12.011","article-title":"Mesenchymal stem cells for bronchopulmonary dysplasia: Phase 1 dose-escalation clinical trial","volume":"164","author":"Chang","year":"2014","journal-title":"J Pediatr"},{"key":"2022022809090132200_sct312351-bib-0023","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.jpeds.2017.02.061","article-title":"Two-year follow-up outcomes of premature infants enrolled in the phase I trial of mesenchymal stem cells transplantation for bronchopulmonary dysplasia","volume":"185","author":"Ahn","year":"2017","journal-title":"J Pediatr"},{"key":"2022022809090132200_sct312351-bib-0024","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":"2022022809090132200_sct312351-bib-0025","doi-asserted-by":"crossref","first-page":"781","DOI":"10.7326\/0003-4819-141-10-200411160-00009","article-title":"Better reporting of harms in randomized trials: An extension of the CONSORT statement","volume":"141","author":"Ioannidis","year":"2004","journal-title":"Ann Intern Med"},{"key":"2022022809090132200_sct312351-bib-0026","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1148\/radiol.11110334","article-title":"New reference values for the neonatal cerebral ventricles","volume":"262","author":"Brouwer","year":"2012","journal-title":"Radiology"},{"key":"2022022809090132200_sct312351-bib-0027","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1159\/000477175","article-title":"Cerebrospinal Fluid Biomarkers of Pediatric Hydrocephalus","volume":"52","author":"Limbrick","year":"2017","journal-title":"Pediatr Neurosurg"},{"key":"2022022809090132200_sct312351-bib-0028","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1203\/00006450-199911000-00014","article-title":"Transforming growth factor-beta1: A possible signal molecule for posthemorrhagic hydrocephalus?","volume":"46","author":"Whitelaw","year":"1999","journal-title":"Pediatr Res"},{"key":"2022022809090132200_sct312351-bib-0029","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1007\/s00381-002-0567-2","article-title":"Vascular endothelial growth factor and erythropoietin concentrations in cerebrospinal fluid of children with hydrocephalus","volume":"18","author":"Koehne","year":"2002","journal-title":"Childs Nerv Syst"},{"key":"2022022809090132200_sct312351-bib-0030","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.ijdevneu.2017.10.001","article-title":"A preliminary evaluation of glial cell line-derived neurotrophic factor (GDNF) levels in cerebrospinal fluid across various gestational ages and clinical conditions of the neonate","volume":"65","author":"Rajkumar","year":"2017","journal-title":"Int J Dev Neurosci"},{"key":"2022022809090132200_sct312351-bib-0031","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/s12987-017-0083-0","article-title":"Chemokine and cytokine levels in the lumbar cerebrospinal fluid of preterm infants with post-hemorrhagic hydrocephalus","volume":"14","author":"Habiyaremye","year":"2017","journal-title":"Fluids Barriers CNS"},{"key":"2022022809090132200_sct312351-bib-0032","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1203\/pdr.0b013e31805341f1","article-title":"Interleukin-1beta, interleukin-18, and interferon-gamma expression in the cerebrospinal fluid of premature infants with posthemorrhagic hydrocephalus\u2013Markers of white matter damage","volume":"61","author":"Schmitz","year":"2007","journal-title":"Pediatr Res"},{"key":"2022022809090132200_sct312351-bib-0033","doi-asserted-by":"crossref","first-page":"F90","DOI":"10.1136\/fn.84.2.F90","article-title":"Brain specific proteins in posthaemorrhagic ventricular dilatation","volume":"84","author":"Whitelaw","year":"2001","journal-title":"Arch Dis Child Fetal Neonatal Ed"},{"key":"2022022809090132200_sct312351-bib-0034","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1227\/NEU.0000000000001415","article-title":"Lumbar cerebrospinal fluid biomarkers of posthemorrhagic hydrocephalus of prematurity: Amyloid precursor protein, soluble amyloid precursor protein alpha, and l1 cell adhesion molecule","volume":"80","author":"Morales","year":"2017","journal-title":"Neurosurgery"},{"key":"2022022809090132200_sct312351-bib-0035","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000323498","article-title":"Biomarkers in neonatal posthemorrhagic hydrocephalus","volume":"101","author":"Merhar","year":"2012","journal-title":"Neonatology"},{"key":"2022022809090132200_sct312351-bib-0036","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1080\/14653240310003611","article-title":"Immunomodulatory effects of fetal and adult mesenchymal stem cells","volume":"5","author":"Le Blanc","year":"2003","journal-title":"Cytotherapy"},{"key":"2022022809090132200_sct312351-bib-0037","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1186\/scrt442","article-title":"Protein synthesis and secretion in human mesenchymal cells derived from bone marrow, adipose tissue and Wharton's jelly","volume":"5","author":"Amable","year":"2014","journal-title":"Stem Cell Res Ther"},{"key":"2022022809090132200_sct312351-bib-0038","doi-asserted-by":"crossref","first-page":"416","DOI":"10.3349\/ymj.2013.54.2.416","article-title":"Long-term (postnatal day 70) outcome and safety of intratracheal transplantation of human umbilical cord blood-derived mesenchymal stem cells in neonatal hyperoxic lung injury","volume":"54","author":"Ahn","year":"2013","journal-title":"Yonsei Med J"},{"key":"2022022809090132200_sct312351-bib-0039","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.3727\/096368915X689640","article-title":"Optimal Timing of Mesenchymal Stem Cell Therapy for Neonatal Intraventricular Hemorrhage","volume":"25","author":"Park","year":"2016","journal-title":"Cell Transplant"},{"key":"2022022809090132200_sct312351-bib-0040","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1097\/01376517-199710000-00002","article-title":"Intraventricular hemorrhage and long-term outcome in the premature infant","volume":"29","author":"Wildrick","year":"1997","journal-title":"J Neurosci Nurs"},{"key":"2022022809090132200_sct312351-bib-0041","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1038\/pr.2012.152","article-title":"Long-term reparative effects of mesenchymal stem cell therapy following neonatal hyperoxia-induced lung injury","volume":"73","author":"Sutsko","year":"2013","journal-title":"Pediatr Res"},{"key":"2022022809090132200_sct312351-bib-0042","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1136\/thoraxjnl-2012-202323","article-title":"Short-term, long-term and paracrine effect of human umbilical cord-derived stem cells in lung injury prevention and repair in experimental bronchopulmonary dysplasia","volume":"68","author":"Pierro","year":"2013","journal-title":"Thorax"},{"key":"2022022809090132200_sct312351-bib-0043","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1016\/j.jcyt.2017.08.004","article-title":"Umbilical cord mesenchymal stromal cell transplantations: A systemic analysis of clinical trials","volume":"19","author":"Can","year":"2017","journal-title":"Cytotherapy"},{"key":"2022022809090132200_sct312351-bib-0044","doi-asserted-by":"crossref","first-page":"F229","DOI":"10.1136\/adc.2010.190173","article-title":"Management of posthaemorrhagic ventricular dilatation","volume":"97","author":"Whitelaw","year":"2012","journal-title":"Arch Dis Child Fetal Neonatal Ed"},{"key":"2022022809090132200_sct312351-bib-0045","doi-asserted-by":"crossref","first-page":"e852","DOI":"10.1542\/peds.2009-1960","article-title":"Randomized trial of drainage, irrigation and fibrinolytic therapy for premature infants with posthemorrhagic ventricular dilatation: Developmental outcome at 2 years","volume":"125","author":"Whitelaw","year":"2010","journal-title":"Pediatrics"}],"container-title":["Stem Cells Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fsctm.17-0219","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/stcltm\/article-pdf\/7\/12\/847\/42625441\/stcltm_7_12_847.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/stcltm\/article-pdf\/7\/12\/847\/42625441\/stcltm_7_12_847.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,28]],"date-time":"2022-02-28T09:09:42Z","timestamp":1646039382000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/stcltm\/article\/7\/12\/847\/6449269"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,8,21]]},"references-count":45,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2018,8,21]]},"published-print":{"date-parts":[[2018,12,1]]}},"URL":"https:\/\/doi.org\/10.1002\/sctm.17-0219","relation":{},"ISSN":["2157-6564","2157-6580"],"issn-type":[{"value":"2157-6564","type":"print"},{"value":"2157-6580","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2018,12,1]]},"published":{"date-parts":[[2018,8,21]]}}}