{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T15:08:01Z","timestamp":1773673681513,"version":"3.50.1"},"reference-count":45,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2007,3,30]],"date-time":"2007-03-30T00:00:00Z","timestamp":1175212800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hepatology Research"],"published-print":{"date-parts":[[2007,4]]},"abstract":"<jats:p><jats:bold>Aim:\u2002<\/jats:bold> Bile duct paucity, ductopenia, is a feature of end\u2010stage chronic cholangiopathies such as primary biliary cirrhosis. The limited proliferative ability of cholangiocytes after specific injury is thought to be the principal cause of ductopenia, although the detailed mechanisms involved are unclear. It has been reported that human amniotic epithelial cells (AEC) express differentiation markers of hepatic parenchymal cells, suggesting a resemblance of AEC to hepatic progenitor cells. The aim of the present study was to develop a mouse model of experimental cholestasis to assess the capability of mouse AEC to trans\u2010differentiate into cholangiocytes.<\/jats:p><jats:p><jats:bold>Methods:\u2002<\/jats:bold> Enhanced green fluorescent protein (EGFP)\u2010transgenic C57BL\/6 pregnant female mice were used as the source of AEC. At 11.5 gestational days, 1 \u00d7 10<jats:sup>5<\/jats:sup> AEC were isolated from EGFP\u2010transgenic mouse embryos and transferred into C57BL\/6 mice. Chronic cholestasis was induced by 0.1%\u03b1\u2010naphthylisothiocyanate (ANIT) feeding immediately after the transfer of AEC. The proliferation of cholangiocytes in the livers was assessed morphologically and immunohistochemically (cytokeratin 7; CK7). The proliferative activity was also quantified immunohistochemically by proliferating cell nuclear antigen (PCNA) protein expression. EGFP of transferred AEC was confirmed by fluorescent laser microscopy and immunofluorescent staining for EGFP. Also, Notch2 and Hes1 expression was evaluated to examine the roles of the differentiation markers in this process.<\/jats:p><jats:p><jats:bold>Results:\u2002<\/jats:bold> Marked proliferation of cholangiocytes was observed in ANIT\u2010fed mice confirmed by quantitative CK7 (3\u20134 fold <jats:italic>vs<\/jats:italic> control) and PCNA (11\u201320 fold <jats:italic>vs<\/jats:italic> control) staining. EGFP and CK7 double positive cells in interlobular bile ducts were confirmed in the livers of AEC\u2010transferred recipients. Positivity of EGFP was further confirmed by the immunofluorescent staining for EGFP. Moreover, both Notch2 and Hes1 expression was confirmed in the proliferative bile duct in this model.<\/jats:p><jats:p><jats:bold>Conclusions:\u2002<\/jats:bold> Significant ductular proliferation was observed in ANIT\u2010fed mice. EGFP\u2010positive cholangiocytes were confirmed in this chronic cholestasis model. AEC transfer was able to contribute to the repopulating of proliferating cholangiocytes under cholestasis, suggesting AEC might be a candidate cell source for stem cell administration in future clinical applications to re\u2010model interlobular bile ducts.<\/jats:p>","DOI":"10.1111\/j.1872-034x.2007.00049.x","type":"journal-article","created":{"date-parts":[[2007,3,30]],"date-time":"2007-03-30T09:16:28Z","timestamp":1175246188000},"page":"286-294","source":"Crossref","is-referenced-by-count":15,"title":["Amniotic epithelial cell\u2013derived cholangiocytes in experimental cholestatic ductal hyperplasia"],"prefix":"10.1111","volume":"37","author":[{"given":"Yuki","family":"Moritoki","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshiyuki","family":"Ueno","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noriatsu","family":"Kanno","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoko","family":"Yamagiwa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koji","family":"Fukushima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. 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