{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T06:49:29Z","timestamp":1760424569937},"reference-count":22,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2004,7,14]],"date-time":"2004-07-14T00:00:00Z","timestamp":1089763200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Gastro and Hepatol"],"published-print":{"date-parts":[[2004,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>Background and Aim:\u2002<\/jats:bold> The toxic milk (<jats:italic>tx<\/jats:italic>) mouse is a non\u2010fatal animal model for the metabolic liver disorder, Wilson's disease. The <jats:italic>tx<\/jats:italic> mouse has a mutated gene for a copper\u2010transporting protein, causing early copper accumulation in the liver and late accumulation in other tissues. The present study investigated the efficacy of liver cell transplantation (LCT) to correct the <jats:italic>tx<\/jats:italic> mouse phenotype.<\/jats:p><jats:p><jats:bold>Methods:\u2002<\/jats:bold> Congenic hepatocytes were isolated and intrasplenically transplanted into 3\u20134\u2010month\u2010old <jats:italic>tx<\/jats:italic> mice, which were then placed on various copper\u2010loaded diets to examine its influence on repopulation by transplanted cells. The control animals were age\u2010matched untransplanted <jats:italic>tx<\/jats:italic> mice. Liver repopulation was determined by comparisons of restriction fragment length polymorphism ratios (DNA and mRNA), and copper levels were measured by atomic absorption spectroscopy.<\/jats:p><jats:p><jats:bold>Results:\u2002<\/jats:bold> Repopulation in recipient <jats:italic>tx<\/jats:italic> mice was detected in 11 of 25 animals (44%) at 4\u2003months after LCT. Dietary copper loading (whether given before or after LCT, or both) provided no growth advantage for donor cells, with similar repopulation incidences in all copper treatment groups. Overall, liver copper levels were significantly lower in repopulated animals (538\u2003\u00b1\u200368\u2003\u00b5g\/g, <jats:italic>n<\/jats:italic>\u2003=\u200311) compared to non\u2010repopulated animals (866\u2003\u00b1\u200362\u2003\u00b5g\/g, <jats:italic>n<\/jats:italic>\u2003=\u200314) and untreated controls (910\u2003\u00b1\u2003103\u2003\u00b5g\/g, <jats:italic>n<\/jats:italic>\u2003=\u20036; <jats:italic>P\u2003<\/jats:italic>&lt;\u20030.05). This effect was also seen in the kidney and spleen. Brain copper levels remained unchanged.<\/jats:p><jats:p><jats:bold>Conclusion:\u2002<\/jats:bold> Transplanted liver cells can proliferate and correct a non\u2010fatal metabolic liver disease, with some restoration of hepatic copper homeostasis after 4\u2003months leading to reduced copper levels in the liver and extrahepatic tissues, but not in the brain.<\/jats:p>","DOI":"10.1111\/j.1440-1746.2004.03451.x","type":"journal-article","created":{"date-parts":[[2004,10,8]],"date-time":"2004-10-08T14:49:14Z","timestamp":1097246954000},"page":"1283-1290","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Liver cell transplantation leads to repopulation and functional correction in a mouse model of Wilson's disease"],"prefix":"10.1111","volume":"19","author":[{"given":"KATRINA J","family":"ALLEN","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"DAPHNE MY","family":"CHEAH","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"PAUL FA","family":"WRIGHT","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"SOPHIE","family":"GAZEAS","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"NICOLE E","family":"PETTIGREW\u2010BUCK","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"YOLANDA H","family":"DEAL","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"JULIAN FB","family":"MERCER","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"ROBERT","family":"WILLIAMSON","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2004,10,8]]},"reference":[{"key":"e_1_2_6_2_2","first-page":"325","volume-title":"Hepatocyte Transplantation.","author":"Strom S","year":"1997"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199805143382004"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.111.6.1262"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0396-266"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2000.20222"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)65574-5"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1006\/mthe.2001.0271"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.jhered.a109751"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/5.10.1619"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.4.361"},{"key":"e_1_2_6_12_2","doi-asserted-by":"crossref","first-page":"G639","DOI":"10.1152\/ajpgi.1999.276.3.G639","article-title":"Hepatocyte\u2010specific localization and copper\u2010dependent trafficking of the Wilson's disease protein in the liver","volume":"39","author":"Schaefer M","year":"1999","journal-title":"Am. 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