{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T20:59:19Z","timestamp":1793912359689,"version":"4.8.0"},"reference-count":14,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2011,12,15]],"date-time":"2011-12-15T00:00:00Z","timestamp":1323907200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2012,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background &amp; Aims<\/jats:title><jats:p>Although regeneration of intrahepatic bile ducts has been extensively studied and intrahepatic progenitor cells have been identified, few studies have focussed on the extrahepatic bile duct (<jats:styled-content style=\"fixed-case\">EHBD<\/jats:styled-content>). We hypothesized that local progenitor cells are present within the <jats:styled-content style=\"fixed-case\">EHBD<\/jats:styled-content> of humans. Human <jats:styled-content style=\"fixed-case\">EHBD<\/jats:styled-content> specimens (<jats:italic>n\u00a0<\/jats:italic>=\u00a017) were included in this study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Specimens of normal <jats:styled-content style=\"fixed-case\">EHBD<\/jats:styled-content> tissue were obtained from healthy donor livers (<jats:italic>n\u00a0<\/jats:italic>=\u00a06), mildly injured <jats:styled-content style=\"fixed-case\">EHBD<\/jats:styled-content> from patients with cholangitis (<jats:italic>n\u00a0<\/jats:italic>=\u00a06) and severely injured <jats:styled-content style=\"fixed-case\">EHBD<\/jats:styled-content> from patients with ischaemic type biliary lesions (<jats:italic>n\u00a0<\/jats:italic>=\u00a05). Double immunostaining for K19 and the proliferation marker Ki\u201067 was performed to identify and localize proliferating cells. In addition, immunofluorescent doublestaining using antibodies against K19 and c\u2010Kit was performed to identify and localize cholangiocytes co\u2010expressing putative progenitor cell markers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In normal <jats:styled-content style=\"fixed-case\">EHBD<\/jats:styled-content>, few Ki\u201067<jats:sup>+<\/jats:sup> cells were detected, whereas large numbers of Ki\u201067<jats:sup>+<\/jats:sup> were found in the diseased <jats:styled-content style=\"fixed-case\">EHBD<\/jats:styled-content>. In <jats:styled-content style=\"fixed-case\">EHBD<\/jats:styled-content> affected by cholangitis, Ki\u201067<jats:sup>+<\/jats:sup> cells were mainly located in the basal layer of the lumen. <jats:styled-content style=\"fixed-case\">EHBD<\/jats:styled-content> specimens from patients with ischaemic type biliary lesions displayed histological signs of epithelial cell loss and large numbers of Ki\u201067<jats:sup>+<\/jats:sup> cells were observed in the peribiliary glands. C\u2010Kit expression was localized throughout the <jats:styled-content style=\"fixed-case\">EHBD<\/jats:styled-content> wall and immunofluorescent doublestaining identified a few K19<jats:sup>+<\/jats:sup>\/c\u2010Kit<jats:sup>+<\/jats:sup> cells in the luminal epithelium of the <jats:styled-content style=\"fixed-case\">EHBD<\/jats:styled-content> as well as in the peribiliary glands.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These findings support the hypothesis that progenitor cells exist in the <jats:styled-content style=\"fixed-case\">EHBD<\/jats:styled-content> and that the peribiliary glands can be considered a local progenitor cell niche in the human <jats:styled-content style=\"fixed-case\">EHBD<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1478-3231.2011.02721.x","type":"journal-article","created":{"date-parts":[[2011,12,16]],"date-time":"2011-12-16T01:53:14Z","timestamp":1324000394000},"page":"554-559","source":"Crossref","is-referenced-by-count":61,"title":["Regeneration of human extrahepatic biliary epithelium: the peribiliary glands as progenitor cell compartment"],"prefix":"10.1111","volume":"32","author":[{"given":"Michael E.","family":"Sutton","sequence":"first","affiliation":[{"name":"Section of Hepatobiliary Surgery and Liver Transplantation Department of Surgery University Medical Center Groningen University of Groningen Groningen The Netherlands"},{"name":"Surgical Research Laboratory University Medical Center Groningen, University of Groningen Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanna","family":"op den Dries","sequence":"additional","affiliation":[{"name":"Section of Hepatobiliary Surgery and Liver Transplantation Department of Surgery University Medical Center Groningen University of Groningen Groningen The Netherlands"},{"name":"Surgical Research Laboratory University Medical Center Groningen, University of Groningen Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirjam H.","family":"Koster","sequence":"additional","affiliation":[{"name":"Surgical Research Laboratory University Medical Center Groningen, University of Groningen Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ton","family":"Lisman","sequence":"additional","affiliation":[{"name":"Section of Hepatobiliary Surgery and Liver Transplantation Department of Surgery University Medical Center Groningen University of Groningen Groningen The Netherlands"},{"name":"Surgical Research Laboratory University Medical Center Groningen, University of Groningen Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette S.H.","family":"Gouw","sequence":"additional","affiliation":[{"name":"Department of Pathology University Medical Center Groningen University of Groningen Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Porte","sequence":"additional","affiliation":[{"name":"Section of Hepatobiliary Surgery and Liver Transplantation Department of Surgery University Medical Center Groningen University of Groningen Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,12,15]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0463.2005.apm_386.x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1524-475x.2001.00467.x"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22218"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510300614"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2009.05.044"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0029(19970915)38:6<552::AID-JEMT2>3.0.CO;2-H"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64765-7"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510300140"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510270218"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00465.2005"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1089\/scd.2007.0037"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ar.1091500304"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2001.21175"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1746.2009.05980.x"}],"container-title":["Liver 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