{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T14:36:04Z","timestamp":1785335764339,"version":"3.55.0"},"reference-count":29,"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":707,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,11,27]],"date-time":"2019-11-27T00:00:00Z","timestamp":1574812800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,11,27]],"date-time":"2019-11-27T00:00:00Z","timestamp":1574812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>We previously reported on the immediate safety and neonatal outcomes of six premature infants with severe bronchopulmonary dysplasia (BPD) who were administered human amnion epithelial cells (hAECs). One infant died in the neonatal period due to unrelated causes. In this study, we aimed to assess the long-term safety and follow-up outcomes of the five surviving infants until 2\u2009years corrected age (CA). hAECs were administered intravenously at a dose of 1 \u00d7\u2009106 cells per kilogram after 36\u2009weeks postconceptional age in infants with established BPD. Study follow-up consisted of assessment of any adverse events, growth, and respiratory, cardiac, and neurodevelopmental outcomes over four time points (6, 12, 18, and 24\u2009months CA). Investigations included chest x-rays, cranial and abdominal ultrasounds, and echocardiograms at regular intervals as well as a magnetic resonance imaging (MRI) brain at 2\u2009years CA. All five infants were alive at 2\u2009years CA. Median time to wean off oxygen was 24 (10-36) months. Two infants had pulmonary hypertension, which resolved by 2\u2009years of age. Four infants were rehospitalized briefly for viral or bacterial infections during the 2\u2009years. MRI brain findings included normal (n = 1), and mild to moderate white matter loss (n = 2). Neurodisabilities diagnosed included hemiplegic cerebral palsy (n = 1), global developmental delay (n = 3), and severe hearing loss (n = 3). No evidence of tumor formation was noted on physical examinations or on any imaging. There were no long-term adverse events observed that could be attributed to hAEC administration. We observed long-term effects of extreme prematurity and severe BPD in the cohort.<\/jats:p>\n               <jats:sec>\n                  <jats:title\/>\n                  <jats:p>Significance statement The long-term safety results of this trial are an important addition to the literature to inform the scientific and clinical community about the impacts of this cell therapy.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1002\/sctm.19-0251","type":"journal-article","created":{"date-parts":[[2019,11,27]],"date-time":"2019-11-27T11:38:23Z","timestamp":1574854703000},"page":"289-294","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Two-year outcomes of infants enrolled in the first-in-human study of amnion cells for bronchopulmonary dysplasia"],"prefix":"10.1093","volume":"9","author":[{"given":"Atul","family":"Malhotra","sequence":"first","affiliation":[{"name":"1 Monash Newborn, Monash Children's Hospital, Clayton, Victoria, Australia"},{"name":"2 The Ritchie Centre Hudson Institute of Medical Research, Monash University, Clayton, Victoria, Australia"},{"name":"3 Department of Paediatrics Monash University, Clayton, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Lim","sequence":"additional","affiliation":[{"name":"2 The Ritchie Centre Hudson Institute of Medical Research, Monash University, Clayton, Victoria, Australia"},{"name":"4 Department of Obstetrics and Gynaecology Monash University, Clayton, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne C.","family":"Mockler","sequence":"additional","affiliation":[{"name":"4 Department of Obstetrics and Gynaecology Monash University, Clayton, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Euan M.","family":"Wallace","sequence":"additional","affiliation":[{"name":"2 The Ritchie Centre Hudson Institute of Medical Research, Monash University, Clayton, Victoria, Australia"},{"name":"4 Department of Obstetrics and Gynaecology Monash University, Clayton, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,11,27]]},"reference":[{"key":"2022022809193629900_sct312633-bib-0001","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1164\/ajrccm.163.7.2011060","article-title":"Bronchopulmonary dysplasia","volume":"163","author":"Jobe","year":"2001","journal-title":"Am J Respir Crit Care Med"},{"key":"2022022809193629900_sct312633-bib-0002","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.jpeds.2018.01.043","article-title":"Bronchopulmonary dysplasia: executive summary of a workshop","volume":"197","author":"Higgins","year":"2018","journal-title":"J Pediatr"},{"key":"2022022809193629900_sct312633-bib-0003","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1056\/NEJMoa1700827","article-title":"Ventilation in extremely preterm infants and respiratory function at 8\u2009years","volume":"377","author":"Doyle","year":"2017","journal-title":"N Engl J Med"},{"key":"2022022809193629900_sct312633-bib-0004","doi-asserted-by":"crossref","first-page":"1601","DOI":"10.1056\/NEJMoa1700827","article-title":"Ventilation in preterm infants and lung function at 8\u2009years","volume":"377","author":"Doyle","year":"2017","journal-title":"N Engl J Med"},{"key":"2022022809193629900_sct312633-bib-0005","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1053\/j.semperi.2018.09.013","article-title":"An update on pulmonary and neurodevelopmental outcomes of bronchopulmonary dysplasia","volume":"42","author":"Cheong","year":"2018","journal-title":"Semin Perinatol"},{"key":"2022022809193629900_sct312633-bib-0006","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1097\/MOP.0000000000000095","article-title":"Disrupted lung development and bronchopulmonary dysplasia: opportunities for lung repair and regeneration","volume":"26","author":"Baker","year":"2014","journal-title":"Curr Opin Pediatr"},{"key":"2022022809193629900_sct312633-bib-0007","doi-asserted-by":"crossref","first-page":"156.e126","DOI":"10.1016\/j.ajog.2011.03.054","article-title":"Human amnion epithelial cells as a treatment for inflammation-induced fetal lung injury in sheep","volume":"205","author":"Vosdoganes","year":"2011","journal-title":"Am J Obstet Gynecol"},{"key":"2022022809193629900_sct312633-bib-0008","doi-asserted-by":"crossref","first-page":"448.e448","DOI":"10.1016\/j.ajog.2012.02.038","article-title":"Human amnion epithelial cells reduce ventilation-induced preterm lung injury in fetal sheep","volume":"206","author":"Hodges","year":"2012","journal-title":"Am J Obstet Gynecol"},{"key":"2022022809193629900_sct312633-bib-0009","article-title":"Stem cell therapy for preventing neonatal diseases in the 21st century: current understanding and challenges","author":"Nitkin","year":"2019","journal-title":"Pediatr Res"},{"key":"2022022809193629900_sct312633-bib-0010","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1542\/peds.2011-2576","article-title":"Cell therapy: a novel treatment approach for bronchopulmonary dysplasia","volume":"130","author":"Vosdoganes","year":"2012","journal-title":"Pediatrics"},{"key":"2022022809193629900_sct312633-bib-0011","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1007\/s00441-016-2517-4","article-title":"Cell-based therapies for neonatal lung disease","volume":"367","author":"O'Reilly","year":"2017","journal-title":"Cell Tissue Res"},{"key":"2022022809193629900_sct312633-bib-0012","doi-asserted-by":"crossref","first-page":"1614","DOI":"10.1016\/j.jcyt.2014.06.004","article-title":"Cell-based therapies for the preterm infant","volume":"16","author":"Zhu","year":"2014","journal-title":"Cytotherapy"},{"key":"2022022809193629900_sct312633-bib-0013","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1161\/STROKEAHA.117.019136","article-title":"Acute or delayed systemic administration of human amnion epithelial cells improves outcomes in experimental stroke","volume":"49","author":"Evans","year":"2018","journal-title":"Stroke"},{"key":"2022022809193629900_sct312633-bib-0014","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1002\/sctm.17-0185","article-title":"Amnion epithelial cell-derived exosomes restrict lung injury and enhance endogenous lung repair","volume":"7","author":"Tan","year":"2018","journal-title":"Stem Cells Translational Medicine"},{"key":"2022022809193629900_sct312633-bib-0015","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1186\/s13287-017-0689-9","article-title":"Human amnion cells reverse acute and chronic pulmonary damage in experimental neonatal lung injury","volume":"8","author":"Zhu","year":"2017","journal-title":"Stem Cell Res Ther"},{"key":"2022022809193629900_sct312633-bib-0016","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1002\/sctm.18-0079","article-title":"First-in-human administration of allogeneic amnion cells in premature infants with bronchopulmonary dysplasia: a safety study","volume":"7","author":"Lim","year":"2018","journal-title":"Stem Cells Translational Medicine"},{"key":"2022022809193629900_sct312633-bib-0017","author":"Murphy","year":"2010"},{"key":"2022022809193629900_sct312633-bib-0018","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.jpeds.2017.05.078","article-title":"Rehospitalization through childhood and adolescence: association with neonatal morbidities in infants of very low birth weight","volume":"188","author":"Kuint","year":"2017","journal-title":"J Pediatr"},{"key":"2022022809193629900_sct312633-bib-0019","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1164\/rccm.201412-2142PP","article-title":"Understanding the short- and long-term respiratory outcomes of prematurity and bronchopulmonary dysplasia","volume":"192","author":"Islam","year":"2015","journal-title":"Am J Respir Crit Care Med"},{"key":"2022022809193629900_sct312633-bib-0020","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.jpeds.2017.10.042","article-title":"Impact of prolonged mechanical ventilation in very low birth weight infants: results from a national cohort study","volume":"194","author":"Choi","year":"2018","journal-title":"J Pediatr"},{"key":"2022022809193629900_sct312633-bib-0021","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1002\/jmv.24962","article-title":"Predictors of prolonged length of hospital stay or readmissions for acute viral lower respiratory tract infections among infants with a history of bronchopulmonary dysplasia","volume":"90","author":"Rodriguez-Martinez","year":"2018","journal-title":"J Med Virol"},{"key":"2022022809193629900_sct312633-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":"2022022809193629900_sct312633-bib-0023","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.jpeds.2019.02.029","article-title":"Safety of intratracheal administration of human umbilical cord blood derived mesenchymal stromal cells in extremely low birth weight preterm infants","volume":"210","author":"Powell","year":"2019","journal-title":"J Pediatr"},{"key":"2022022809193629900_sct312633-bib-0024","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":"2022022809193629900_sct312633-bib-0025","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0047559","article-title":"Safety of cell therapy with mesenchymal stromal cells (SafeCell): a systematic review and meta-analysis of clinical trials","volume":"7","author":"Lalu","year":"2012","journal-title":"PLoS One"},{"key":"2022022809193629900_sct312633-bib-0026","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2018-026265","article-title":"Human amnion cells for the prevention of bronchopulmonary dysplasia: a protocol for a phase I dose escalation study","volume":"9","author":"Baker","year":"2019","journal-title":"BMJ Open"},{"key":"2022022809193629900_sct312633-bib-0027","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1016\/j.jpeds.2013.11.036","article-title":"Feasibility of autologous cord blood cells for infants with hypoxic-ischemic encephalopathy","volume":"164","author":"Cotten","year":"2014","journal-title":"J Pediatr"},{"key":"2022022809193629900_sct312633-bib-0028","doi-asserted-by":"crossref","first-page":"2071","DOI":"10.1002\/sctm.17-0102","article-title":"Effect of autologous cord blood infusion on motor function and brain connectivity in young children with cerebral palsy: a randomized, placebo-controlled trial","volume":"6","author":"Sun","year":"2017","journal-title":"Stem Cells Translational Medicine"},{"key":"2022022809193629900_sct312633-bib-0029","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1002\/sctm.16-0474","article-title":"Autologous cord blood infusions are safe and feasible in young children with autism spectrum disorder: results of a single-center phase I open-label trial","volume":"6","author":"Dawson","year":"2017","journal-title":"Stem Cells Translational Medicine"}],"container-title":["Stem Cells Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/sctm.19-0251","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/sctm.19-0251","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/stcltm\/article-pdf\/9\/3\/289\/42628911\/stcltm_9_3_289.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/stcltm\/article-pdf\/9\/3\/289\/42628911\/stcltm_9_3_289.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,28]],"date-time":"2022-02-28T09:21:32Z","timestamp":1646040092000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/stcltm\/article\/9\/3\/289\/6407105"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,27]]},"references-count":29,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2019,11,27]]},"published-print":{"date-parts":[[2020,3,1]]}},"URL":"https:\/\/doi.org\/10.1002\/sctm.19-0251","relation":{},"ISSN":["2157-6564","2157-6580"],"issn-type":[{"value":"2157-6564","type":"print"},{"value":"2157-6580","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,3,1]]},"published":{"date-parts":[[2019,11,27]]},"assertion":[{"value":"2019-08-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-10-29","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-11-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}