{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:08:39Z","timestamp":1792786119505,"version":"4.5.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2023,6,7]],"date-time":"2023-06-07T00:00:00Z","timestamp":1686096000000},"content-version":"vor","delay-in-days":6,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Duke Clinical and Translational Science Institute"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,6,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Hypoxic ischemic encephalopathy (HIE) in neonates causes increased mortality and long-term morbidity in surviving babies. Hypothermia (HT) has improved outcomes, however, mortality remains high with ~half of surviving babies developing neurological impairment in their first years. We previously explored the use of autologous cord blood (CB) to determine if CB cells could lessen long-term damage to the brain. However, the feasibility of CB collection from sick neonates limited the utility of this approach. Allogeneic cord tissue mesenchymal stromal cells (hCT-MSC), cryopreserved and readily available, have been shown to ameliorate brain injury in animal models of HIE. We, therefore, conducted a pilot, phase I, clinical trial to test the safety and describe the preliminary efficacy of hCT-MSC in neonates with HIE.<\/jats:p>\n                  <jats:p>The study treated infants with moderate to severe HIE, treated with HT, with 1 or 2 doses of 2 million cells\/kg\/dose of hCT-MSC given intravenously. The babies were randomized to receive 1 or 2 doses with the first dose during HT and the second dose 2 months later. Babies were followed for survival and development with scoring of Bayley\u2019s at 12 postnatal months.<\/jats:p>\n                  <jats:p>Six neonates with moderate (4) or severe (2) HIE were enrolled. All received 1 dose of hCT-MSC during HT and 2 received a 2nd dose, 2 months later. hCT-MSC infusions were well tolerated although 5\/6 babies developed low titer anti-HLA antibodies by 1 year of age. All babies survived, with average to low-average developmental assessment standard scores for ages between 12 and 17 postnatal months. Further study is warranted.<\/jats:p>","DOI":"10.1093\/stcltm\/szad027","type":"journal-article","created":{"date-parts":[[2023,5,24]],"date-time":"2023-05-24T19:21:15Z","timestamp":1684956075000},"page":"355-364","source":"Crossref","is-referenced-by-count":50,"title":["A Pilot Phase I Trial of Allogeneic Umbilical Cord Tissue-Derived Mesenchymal Stromal Cells in Neonates With Hypoxic-Ischemic Encephalopathy"],"prefix":"10.1093","volume":"12","author":[{"given":"Charles Michael","family":"Cotten","sequence":"first","affiliation":[{"name":"Division of Neonatology, Department of Pediatrics, Duke University School of Medicine , Durham, NC , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberley","family":"Fisher","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Department of Pediatrics, Duke University School of Medicine , Durham, NC , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Malcolm","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Department of Pediatrics, Duke University School of Medicine , Durham, NC , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn E","family":"Gustafson","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Department of Pediatrics, Duke University School of Medicine , Durham, NC , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynn","family":"Cheatham","sequence":"additional","affiliation":[{"name":"Marcus Center for Cellular Cures, Duke University School of Medicine , Durham, NC , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Marion","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Department of Pediatrics, Duke University School of Medicine , Durham, NC , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Greenberg","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Department of Pediatrics, Duke University School of Medicine , Durham, NC , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3370-0703","authenticated-orcid":false,"given":"Joanne","family":"Kurtzberg","sequence":"additional","affiliation":[{"name":"Marcus Center for Cellular Cures, Duke University School of Medicine , Durham, NC , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,6,15]]},"reference":[{"issue":"15","key":"2023061506101986800_CIT0001","doi-asserted-by":"crossref","first-page":"1574","DOI":"10.1056\/NEJMcps050929","article-title":"Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy","volume":"353","author":"Shankaran","year":"2005","journal-title":"N Engl J Med"},{"issue":"14","key":"2023061506101986800_CIT0002","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1056\/NEJMoa0900854","article-title":"Moderate hypothermia to treat perinatal asphyxial encephalopathy","volume":"361","author":"Azzopardi","year":"2009","journal-title":"N Engl J Med"},{"issue":"8","key":"2023061506101986800_CIT0003","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1001\/archpediatrics.2011.43","article-title":"Whole-body hypothermia for term and near-term newborns with hypoxic-ischemic encephalopathy: a randomized controlled trial","volume":"165","author":"Jacobs","year":"2011","journal-title":"Arch Pediatr Adolesc Med"},{"issue":"4","key":"2023061506101986800_CIT0004","doi-asserted-by":"crossref","first-page":"e771","DOI":"10.1542\/peds.2009-2441","article-title":"Systemic hypothermia after neonatal \u00adencephalopathy: outcomes of neo.nEURO.network RCT","volume":"126","author":"Simbruner","year":"2010","journal-title":"Pediatrics"},{"issue":"2","key":"2023061506101986800_CIT0005","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/S1474-4422(15)00347-6","article-title":"Moderate hypothermia within 6 h of birth plus inhaled xenon versus moderate hypothermia alone after birth asphyxia (TOBY-Xe): a proof-of-concept, open-label, randomised controlled trial","volume":"15","author":"Azzopardi","year":"2016","journal-title":"Lancet Neurol"},{"issue":"4","key":"2023061506101986800_CIT0006","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1159\/000486820","article-title":"High-dose erythropoietin for asphyxia and encephalopathy (HEAL): a randomized controlled trial - 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