title: Regeneration of human extrahepatic biliary epithelium: the peribiliary glands as progenitor cell compartment.
abstract: OBJECTIVE
  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 (EHBD). We hypothesized that local progenitor cells are present within the EHBD of humans. Human EHBD specimens (n = 17) were included in this study.
  
  
  METHODS
  Specimens of normal EHBD tissue were obtained from healthy donor livers (n = 6), mildly injured EHBD from patients with cholangitis (n = 6) and severely injured EHBD from patients with ischaemic type biliary lesions (n = 5). Double immunostaining for K19 and the proliferation marker Ki-67 was performed to identify and localize proliferating cells. In addition, immunofluorescent doublestaining using antibodies against K19 and c-Kit was performed to identify and localize cholangiocytes co-expressing putative progenitor cell markers.
  
  
  RESULTS
  In normal EHBD, few Ki-67(+) cells were detected, whereas large numbers of Ki-67(+) were found in the diseased EHBD. In EHBD affected by cholangitis, Ki-67(+) cells were mainly located in the basal layer of the lumen. EHBD specimens from patients with ischaemic type biliary lesions displayed histological signs of epithelial cell loss and large numbers of Ki-67(+) cells were observed in the peribiliary glands. C-Kit expression was localized throughout the EHBD wall and immunofluorescent doublestaining identified a few K19(+) /c-Kit(+) cells in the luminal epithelium of the EHBD as well as in the peribiliary glands.
  
  
  CONCLUSIONS
  These findings support the hypothesis that progenitor cells exist in the EHBD and that the peribiliary glands can be considered a local progenitor cell niche in the human EHBD.
authors.affiliation: Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Sutton
authors.forename: Sanna
authors.initials: S
authors.lastname: op den Dries
authors.forename: Mirjam H
authors.initials: MH
authors.lastname: Koster
authors.forename: Ton
authors.initials: T
authors.lastname: Lisman
authors.forename: Annette S H
authors.initials: AS
authors.lastname: Gouw
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Porte
mesh_terms: D017734:Bile Ducts, Extrahepatic / Q000166:cytology* / Q000473:pathology; D004702:Endocrine Glands / Q000166:cytology*; D004848:Epithelium / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D053552:Keratin-7; D019394:Ki-67 Antigen; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D012038:Regeneration / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology*
chemical_list: D053552:Keratin-7; D019394:Ki-67 Antigen; D019009:Proto-Oncogene Proteins c-kit