{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T01:16:27Z","timestamp":1773796587640,"version":"3.50.1"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2024,4,15]],"date-time":"2024-04-15T00:00:00Z","timestamp":1713139200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,6,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Placenta-derived human amniotic epithelial cells (hAEC) exhibit anti-inflammatory and anti-fibrotic effects in cirrhosis models. We conducted a first-in-human phase I clinical trial to assess the safety and tolerability of hAEC in adults with compensated cirrhosis. We examined increasing and repeated doses of hAEC in 9 patients in 3 cohorts. Cohort 1 patients received 0.5\u2005\u00d7\u2005106\/kg hAEC in one IV infusion. Cohort 2 patients received 1\u2005\u00d7\u2005106\/kg hAEC in one IV infusion. The patients in cohort 3 received 1\u2005\u00d7\u2005106\/kg hAEC on days 0 and 28. Here, we report follow-up to post-infusion day 56 (D56), during which no serious adverse events occurred. Six patients experienced no study-related adverse events, while 3 patients reported mild (grade 1) headaches that were possibly infusion-related. A transient decrease in serum platelet count occurred in all patients, which returned to baseline screening values by day 5. FIB-4 values to assess fibrosis were significantly lower at D56. Although not statistically significant, serum AST levels and liver stiffness measurements at D56 were lower than those at baseline. The hepatic venous pressure gradient, a measure of portal hypertension, declined in 4 patients, did not change in 3 patients, and increased in 2 patients. In conclusion, intravenous infusion of allogeneic hAEC in patients with compensated cirrhosis at the doses used in this study was safe and well tolerated, with no difference observed between 1 and 2 doses. Decreased hepatic inflammation, liver stiffness, and portal hypertension support larger studies aimed at identifying patients who may benefit from this therapy.<\/jats:p>\n               <jats:p>Clinical Trial registration: The trial was prospectively entered on the Australian Clinical Trials Registry (ANZCTR12616000437460).<\/jats:p>","DOI":"10.1093\/stcltm\/szae023","type":"journal-article","created":{"date-parts":[[2024,4,15]],"date-time":"2024-04-15T10:48:31Z","timestamp":1713178111000},"page":"522-531","source":"Crossref","is-referenced-by-count":8,"title":["Human Amniotic Epithelial Cell Transplantation is Safe and Well Tolerated in Patients with Compensated Cirrhosis: A First-in-Human Trial"],"prefix":"10.1093","volume":"13","author":[{"given":"Rebecca","family":"Lim","sequence":"first","affiliation":[{"name":"The Ritchie Centre, Hudson Institute of Medical Research , 27-31 Wright Street, Clayton, Melbourne 3168 , Australia"},{"name":"Department of Obstetrics and Gynecology, Monash University , 246 Clayton Road, Clayton, Melbourne 3168 , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Hodge","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Eastern Health , 5 Arnold Street, Box Hill, Melbourne 3128, \u00a0 Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sherryne","family":"Warner","sequence":"additional","affiliation":[{"name":"School of Clinical Sciences, Monash University , 246 Clayton Road, Clayton, Melbourne 3168 , Australia"},{"name":"The John Goldman Centre for Cellular Therapy, Hammersmith Hospital , Ducane Road, London W12 OHS, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory T","family":"Moore","sequence":"additional","affiliation":[{"name":"School of Clinical Sciences, Monash University , 246 Clayton Road, Clayton, Melbourne 3168 , Australia"},{"name":"The John Goldman Centre for Cellular Therapy, Hammersmith Hospital , Ducane Road, London W12 OHS, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeanne","family":"Correia","sequence":"additional","affiliation":[{"name":"The John Goldman Centre for Cellular Therapy, Hammersmith Hospital , Ducane Road, London W12 OHS, United Kingdom"},{"name":"The Ritchie Centre, Hudson Institute of Medical Research , 27-31 Wright Street, Clayton, Melbourne 3168 , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mirja","family":"Krause","sequence":"additional","affiliation":[{"name":"The Ritchie Centre, Hudson Institute of Medical Research , 27-31 Wright Street, Clayton, Melbourne 3168 , Australia"},{"name":"Department of Obstetrics and Gynecology, Monash University , 246 Clayton Road, Clayton, Melbourne 3168 , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hannah","family":"McDonald","sequence":"additional","affiliation":[{"name":"The Ritchie Centre, Hudson Institute of Medical Research , 27-31 Wright Street, Clayton, Melbourne 3168 , Australia"},{"name":"Department of Gastroenterology, Monash Health , 246 Clayton Raod, Clayton, Melbourne 3168 , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siow T","family":"Chan","sequence":"additional","affiliation":[{"name":"The Ritchie Centre, Hudson Institute of Medical Research , 27-31 Wright Street, Clayton, Melbourne 3168 , Australia"},{"name":"Department of Obstetrics and Gynecology, Monash University , 246 Clayton Road, Clayton, Melbourne 3168 , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mihiri","family":"Goonetilleke","sequence":"additional","affiliation":[{"name":"The Ritchie Centre, Hudson Institute of Medical Research , 27-31 Wright Street, Clayton, Melbourne 3168 , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stuart M","family":"Lyon","sequence":"additional","affiliation":[{"name":"Diagnostic Imaging Department, Monash Health , 246 Clayton Road, Clayton, Melbourne 3168 , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7829-0974","authenticated-orcid":false,"given":"William","family":"Sievert","sequence":"additional","affiliation":[{"name":"School of Clinical Sciences, Monash University , 246 Clayton Road, Clayton, Melbourne 3168 , Australia"},{"name":"The John Goldman Centre for Cellular Therapy, Hammersmith Hospital , Ducane Road, London W12 OHS, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,6,10]]},"reference":[{"issue":"1","key":"2024061106303278000_CIT0001","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.jhep.2018.09.014","article-title":"Burden of liver diseases in the world","volume":"70","author":"Asrani","year":"2019","journal-title":"J Hepatol"},{"issue":"9865","key":"2024061106303278000_CIT0002","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1016\/S0140-6736(12)61425-1","article-title":"Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study","volume":"381","author":"Marcellin","year":"2013","journal-title":"Lancet"},{"key":"2024061106303278000_CIT0003","first-page":"577","article-title":"Stem cells derived from human fetal membranes display multilineage differentiation potential","volume-title":"Biol Reprod","author":"Ilancheran","year":"2007"},{"key":"2024061106303278000_CIT0004","first-page":"1340","article-title":"Human amnion-derived cells as a reliable source of stem cells","volume-title":"Curr Mol Med","author":"Saito","year":"2012"},{"issue":"9","key":"2024061106303278000_CIT0005","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.3727\/096368910X504496","article-title":"Transplantation of human amnion epithelial cells reduces hepatic fibrosis in immunocompetent CCl4-treated mice","volume":"19","author":"Manuelpillai","year":"2010","journal-title":"Cell Transplant"},{"key":"2024061106303278000_CIT0006","first-page":"e38631","article-title":"hAEC transplantation induces markers of alternative macrophage activation and reduces established hepatic fibrosis","volume-title":"PLoS One","author":"Manuelpillai","year":"2012"},{"issue":"8","key":"2024061106303278000_CIT0007","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1016\/j.jcyt.2014.01.005","article-title":"Soluble factors derived from human amniotic epithelial cells suppress collagen production in human hepatic stellate cells","volume":"16","author":"Hodge","year":"2014","journal-title":"Cytotherapy"},{"key":"2024061106303278000_CIT0008","first-page":"1441","article-title":"Human amnion epithelial cells and their soluble factors reduce liver fibrosis in murine non-alcoholic steatohepatitis","volume-title":"J Gastroenterol 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study","volume":"12","author":"Ka","year":"2023","journal-title":"Stem Cells Transl Med"},{"key":"2024061106303278000_CIT0016","first-page":"204","article-title":"The assessment of mesenchymal stem cells therapy in acute on chronic liver failure and chronic liver disease: a systematic review and meta-analysis of randomised controlled clinical trials","volume-title":"Stem Cell Res Ther","author":"Liu","year":"2022"},{"key":"2024061106303278000_CIT0017","first-page":"1047907","article-title":"MSCs can be a double-edged sword in tumorigenesis","volume-title":"Front Oncol","author":"Zhang","year":"2022"},{"key":"2024061106303278000_CIT0018","first-page":"e6657","article-title":"Fibrogenic potential of human multipotent mesenchymal stromal cells in injured liver","volume-title":"PLoS One","author":"Baertschiger","year":"2009"},{"key":"2024061106303278000_CIT0019","first-page":"166","article-title":"Clinical outcomes of the transplantation of stem cells from various human tissue sources in the management of liver cirrhosis: a systematic review and meta-analysis","volume-title":"Curr Stem Cell Res Ther","author":"Qi","year":"2015"},{"issue":"3","key":"2024061106303278000_CIT0020","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1111\/j.1478-3231.2010.02424.x","article-title":"Bone marrow mononuclear cell therapy for patients with cirrhosis: a phase 1 study","volume":"31","author":"Couto","year":"2011","journal-title":"Liver Int"},{"issue":"1_suppl","key":"2024061106303278000_CIT0021","doi-asserted-by":"crossref","first-page":"S105","DOI":"10.3727\/000000006783982395","article-title":"Hepatocyte transplantation: clinical experience and potential for future use","volume":"15","author":"Strom","year":"2006","journal-title":"Cell Transplant"},{"key":"2024061106303278000_CIT0022","first-page":"1261","article-title":"Hepatocyte cell therapy in liver disease","volume-title":"Exp Rev Gastroenterol 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(I-ACT)","volume":"17","author":"Phan","year":"2023","journal-title":"Front Neurosci"}],"container-title":["Stem Cells Translational 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