{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T09:47:14Z","timestamp":1790156834895,"version":"4.0.1"},"reference-count":42,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2015,5,26]],"date-time":"2015-05-26T00:00:00Z","timestamp":1432598400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"},{"start":{"date-parts":[[2015,5,26]],"date-time":"2015-05-26T00:00:00Z","timestamp":1432598400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"European Union INNOVALIV, FP7-HEALTH-2011","award":["278152"],"award-info":[{"award-number":["278152"]}]},{"name":"Generalitat Valenciana-Conselleria de Educaci\u00f3n","award":["GV2014\/116"],"award-info":[{"award-number":["GV2014\/116"]}]},{"name":"Instituto de Salud Carlos III\u201d from the Spanish Ministry of Economy and Competitiveness","award":["CD11\/00007"],"award-info":[{"award-number":["CD11\/00007"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver Transpl"],"published-print":{"date-parts":[[2015,6]]},"abstract":"<jats:p>Crigler\u2010Najjar type 1 disease is a rare inherited metabolic disease characterized by high levels of unconjugated bilirubin due to the complete absence of hepatic uridine diphosphoglucuronate\u2013glucuronosyltransferase activity. Hepatocyte transplantation (HT) has been proposed as an alternative treatment for Crigler\u2010Najjar syndrome, but it is still limited by the quality and the low engraftment and repopulation ability of the cells used. Because of their attachment capability and expression of adhesion molecules as well as the higher proportion of hepatic progenitor cells, neonatal hepatocytes may have an advantage over adult cells. Adult or neonatal hepatocytes were transplanted into Gunn rats, a model for Crigler\u2010Najjar disease. Engraftment and repopulation were studied and compared by immunofluorescence (IF). Additionally, the serum bilirubin levels, the presence of bilirubin conjugates in rat serum, and the expression of uridine diphosphate glucuronosyltransferase 1 family polypeptide A1 (UGT1A1) in rat liver samples were also analyzed. Here we show that neonatal HT results in long\u2010term correction in Gunn rats. In comparison with adult cells, neonatal cells showed better engraftment and repopulation capability 3 days and 6 months after transplantation, respectively. Bilirubinemia decreased in the transplanted animals during the whole experimental follow\u2010up (6 months). Bilirubin conjugates were also present in the serum of the transplanted animals. Western blots and IF confirmed the presence and expression of UGT1A1 in the liver. This work is the first to demonstrate the advantage of using neonatal hepatocytes for the treatment of Crigler\u2010Najjar in vivo. <jats:italic toggle=\"yes\">Liver Transpl 21:801\u2010811, 2015<\/jats:italic>. \u00a9 2015 AASLD.<\/jats:p>","DOI":"10.1002\/lt.24121","type":"journal-article","created":{"date-parts":[[2015,3,30]],"date-time":"2015-03-30T07:19:13Z","timestamp":1427699953000},"page":"801-811","source":"Crossref","is-referenced-by-count":16,"title":["Human neonatal hepatocyte transplantation induces long\u2010term rescue of unconjugated hyperbilirubinemia in the Gunn rat"],"prefix":"10.1097","volume":"21","author":[{"given":"Laia","family":"Tolosa","sequence":"first","affiliation":[{"name":"Unidad de Hepatolog\u00eda Experimental,Instituto de Investigaci\u00f3n Sanitaria La Fe,Valencia,Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"L\u00f3pez","sequence":"additional","affiliation":[{"name":"Unidad de Hepatolog\u00eda Experimental,Instituto de Investigaci\u00f3n Sanitaria La Fe,Valencia,Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugenia","family":"Pareja","sequence":"additional","affiliation":[{"name":"Unidad de Cirug\u00eda Hepatobiliopancre\u00e1tica y Transplante Hep\u00e1tico,Hospital La Fe,Valencia,Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Teresa","family":"Donato","sequence":"additional","affiliation":[{"name":"Unidad de Hepatolog\u00eda Experimental,Instituto de Investigaci\u00f3n Sanitaria La Fe,Valencia,Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas,Fondo de Investigaciones Sanitarias,Barcelona,Spain"},{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular, Facultad de Medicina,Universidad de Valencia,Valencia,Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Myara","sequence":"additional","affiliation":[{"name":"Service de Biologie,Groupe Hospitalier Saint Joseph,Paris,France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuan Huy","family":"Nguyen","sequence":"additional","affiliation":[{"name":"INSERM Unit\u00e9s Mixtes de Recherche en Sant\u00e9 1064,Centre Hospitalier Universitaire H\u00f4tel Dieu,Nantes,France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Vicente","family":"Castell","sequence":"additional","affiliation":[{"name":"Unidad de Hepatolog\u00eda Experimental,Instituto de Investigaci\u00f3n Sanitaria La Fe,Valencia,Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas,Fondo de Investigaciones Sanitarias,Barcelona,Spain"},{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular, Facultad de Medicina,Universidad de Valencia,Valencia,Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Jos\u00e9","family":"G\u00f3mez\u2010Lech\u00f3n","sequence":"additional","affiliation":[{"name":"Unidad de Hepatolog\u00eda Experimental,Instituto de Investigaci\u00f3n Sanitaria La Fe,Valencia,Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas,Fondo de Investigaciones Sanitarias,Barcelona,Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2015,5,26]]},"reference":[{"key":"lt24121-bib-0001-20240115","doi-asserted-by":"crossref","first-page":"151","DOI":"10.3727\/000000005783983250","article-title":"Isolated hepatocyte transplantation for Crigler\u2010Najjar syndrome type 1","volume":"14","year":"2005","journal-title":"Cell 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Transplant"},{"key":"lt24121-bib-0009-20240115","doi-asserted-by":"crossref","first-page":"2267","DOI":"10.3727\/096368912X637505","article-title":"Clinical outcome of hepatocyte transplantation in four pediatric patients with inherited metabolic diseases","volume":"21","year":"2012","journal-title":"Cell Transplant"},{"key":"lt24121-bib-0010-20240115","first-page":"1","article-title":"Hepatocyte cryopreservation: is it time to change the strategy?","volume":"16","year":"2010","journal-title":"World J Gastroenterol"},{"key":"lt24121-bib-0011-20240115","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1097\/TP.0b013e31821aba37","article-title":"Influence of platelet lysate on the recovery and metabolic performance of cryopreserved human hepatocytes upon thawing","volume":"91","year":"2011","journal-title":"Transplantation"},{"key":"lt24121-bib-0012-20240115","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.3727\/096368913X669743","article-title":"Neonatal livers: a 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Animal model: hereditary nonhemolytic unconjugated hyperbilirubinemia in Gunn rats","volume":"69","year":"1972","journal-title":"Am J Pathol"},{"key":"lt24121-bib-0018-20240115","first-page":"149","article-title":"Gunn rat: a model for inherited deficiency of bilirubin glucuronidation","volume":"37","year":"1993","journal-title":"Adv Vet Sci Comp Med"},{"key":"lt24121-bib-0019-20240115","doi-asserted-by":"crossref","first-page":"21","DOI":"10.3727\/096368909X474267","article-title":"Functional characterization of hepatocytes for cell transplantation: customized cell preparation for each receptor","volume":"19","year":"2010","journal-title":"Cell Transplant"},{"key":"lt24121-bib-0020-20240115","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1016\/j.ymthe.2005.06.482","article-title":"Therapeutic lentivirus\u2010mediated neonatal in vivo gene therapy in hyperbilirubinemic Gunn rats","volume":"12","year":"2005","journal-title":"Mol 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Studies on the control of cytokinesis in vivo","volume":"74","year":"1972","journal-title":"Exp Cell Res"},{"key":"lt24121-bib-0037-20240115","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.clinre.2011.05.011","article-title":"Polyploidy and liver proliferation","volume":"36","year":"2012","journal-title":"Clin Res Hepatol Gastroenterol"},{"key":"lt24121-bib-0038-20240115","doi-asserted-by":"crossref","first-page":"657","DOI":"10.3109\/14653249.2012.663526","article-title":"Fetal liver\u2010derived mesenchymal stromal cells augment engraftment of transplanted hepatocytes","volume":"14","year":"2012","journal-title":"Cytotherapy"},{"key":"lt24121-bib-0039-20240115","first-page":"65","article-title":"Liver engraftment and repopulation by in vitro expanded adult derived human liver stem cells in a child with ornithine carbamoyltransferase deficiency","volume":"13","year":"2014","journal-title":"JIMD Rep"},{"key":"lt24121-bib-0040-20240115","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1111\/j.1365-2184.2005.00338.x","article-title":"Hepatic proliferation in Gunn rats transplanted with hepatocytes: effect of retrorsine and tri\u2010iodothyronine","volume":"38","year":"2005","journal-title":"Cell Prolif"},{"key":"lt24121-bib-0041-20240115","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1136\/gut.2007.127969","article-title":"Liver repopulation with bone marrow derived cells improves the metabolic disorder in the Gunn rat","volume":"56","year":"2007","journal-title":"Gut"},{"key":"lt24121-bib-0042-20240115","doi-asserted-by":"crossref","first-page":"10,553","DOI":"10.3748\/wjg.v20.i30.10553","article-title":"Human liver stem\/progenitor cells decrease serum bilirubin in hyperbilirubinemic Gunn rat","volume":"20","year":"2014","journal-title":"World J Gastroenterol"}],"container-title":["Liver Transplantation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Flt.24121","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Flt.24121","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/01445473-201506000-00011","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,15]],"date-time":"2024-01-15T01:07:53Z","timestamp":1705280873000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/01445473-201506000-00011"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,5,26]]},"references-count":42,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2015]]}},"URL":"https:\/\/doi.org\/10.1002\/lt.24121","relation":{},"ISSN":["1527-6465","1527-6473"],"issn-type":[{"value":"1527-6465","type":"print"},{"value":"1527-6473","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,5,26]]}}}