{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T10:05:52Z","timestamp":1770977152132,"version":"3.50.1"},"reference-count":36,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2013,5,20]],"date-time":"2013-05-20T00:00:00Z","timestamp":1369008000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Xenotransplantation"],"published-print":{"date-parts":[[2013,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>We previously generated humanized chimeric mice by transplanting h\u2010hepatocytes into the livers of the diseased\u2010liver transgenic mouse model with immunodeficient background. These mice with livers mostly replaced by human (h) hepatocytes have been proved to be useful for research on drug metabolism and toxicity and on intrahepatic pathogens such as hepatitis. However, their small body size prohibited collecting sufficient biological samples and made surgical manipulation difficult, which motivated us to produce humanized larger animal(s) bearing h\u2010hepatocytes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Fischer 344 (F344) rats at 2\u00a0weeks of age were administrated with hepatotoxin retrorsine (RS) and then transplanted with syngeneic F344 rat (r)\u2010 or h\u2010hepatocytes via the portal vein. The hosts were injected daily with FK506 immunosuppressant. The livers were harvested periodically for determining donor\u2010cell replacement ratios and compared with those of the humanized chimeric mice, and liver\u2010specific<jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content>and protein expressions by immunohistochemistry and reverse\u2010transcription PCR.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>RS treatment of infant rats inhibited hepatocyte proliferation, resulting in decreased liver weight and megalocytic changes in hepatocytes. R\u2010hepatocytes transplanted into RS\u2010treated rats engrafted into and repopulated the liver at ratios of 16.4\u00a0\u00b1\u00a06.7% and 48.3\u00a0\u00b1\u00a029.3% at 3 and 6\u00a0weeks after transplantation, respectively. H\u2010hepatocytes also engrafted into the rat liver and showed a repopulation ratio of 2.5\u00a0\u00b1\u00a01.5% at 3\u00a0weeks post\u2010transplantation, which was comparable to the ratio in the humanized chimeric mouse model at least until 3\u00a0weeks. Propagated h\u2010hepatocytes in the rat liver expressed hepatocyte\u2010specific<jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content>and proteins at least 3\u00a0weeks after transplantation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Xenogeneic hepatocytes were able to engraft rat liver and grow well therein for at least 3\u00a0weeks post\u2010transplantation in rats when immunosuppression was combined appropriately with liver injury at comparable levels to the well\u2010characterized humanized chimeric mouse model.<\/jats:p><\/jats:sec>","DOI":"10.1111\/xen.12037","type":"journal-article","created":{"date-parts":[[2013,5,20]],"date-time":"2013-05-20T04:44:42Z","timestamp":1369025082000},"page":"227-238","source":"Crossref","is-referenced-by-count":15,"title":["Repopulation of the immunosuppressed retrorsine\u2010treated infant rat liver with human hepatocytes"],"prefix":"10.1111","volume":"20","author":[{"given":"Asato","family":"Tachibana","sequence":"first","affiliation":[{"name":"Yoshizato Project, Cooperative Link of Unique Science and Technology for Economy Revitalization (CLUSTER) Hiroshima Prefectural Institute of Industrial Science and Technology Higashihiroshima Hiroshima Japan"},{"name":"PhoenixBio Co. 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