title: Wholesale hepatocytic differentiation in the rat from ductular oval cells, the progeny of biliary stem cells.
abstract: OBJECTIVE
  Biliary epithelial cells (ductular oval cells) migrate into the periportal and midzonal parenchyma when hepatocyte regeneration after injury is significantly impeded. The potential of oval cells to differentiate into hepatocytes has been questioned. We have sought to resolve this issue using the modified Solt-Farber procedure in which 2-acetylaminofluorene is used to block hepatocyte regeneration in partially hepatectomized rats.
  
  
  METHODS
  Rats received 2-acetylaminofluorene by oral gavage for 6 days before and up to 7 days after a two-thirds hepatectomy. The cellular reaction was visualized by the immunohistochemical localization of intermediate filaments cytokeratins 8 and 19 and vimentin, cytochrome P450 enzymatic proteins and alpha-foetoprotein. Expression of albumin and alpha-foetoprotein mRNA transcripts were observed in situ using antisense riboprobes.
  
  
  RESULTS
  During the first 9 days after partial hepatectomy long strings of ductular cells spread outwards from the portal areas. These cells exhibited strong diffuse cytoplasmic staining with the anticytokeratin 8 and 19 antibodies, like authentic bile ducts, but in addition also expressed vimentin and alpha-foetoprotein (protein and mRNA)-collectively termed the "oval cell phenotype". Thereafter, these ducts rapidly vanished to be replaced by basophilic hepatocytes which lacked the oval cell phenotype, but which acquired strong expression of albumin mRNA. At 14 days after partial hepatectomy the oval cell phenotype was restricted to the peripheral margins of the newborn periportal hepatocytes, the distal tips of the oval cell ducts, and these too had disappeared within another 7 days.
  
  
  CONCLUSIONS
  Ductular oval cells will differentiate into hepatocytes under appropriate experimental conditions.
authors.affiliation: Department of Histopathology, Royal Postgraduate Medical School, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Alison
authors.forename: M
authors.initials: M
authors.lastname: Golding
authors.forename: E N
authors.initials: EN
authors.lastname: Lalani
authors.forename: P
authors.initials: P
authors.lastname: Nagy
authors.forename: S
authors.initials: S
authors.lastname: Thorgeirsson
authors.forename: C
authors.initials: C
authors.lastname: Sarraf
mesh_terms: D000418:Albumins / Q000032:analysis; D000818:Animals; D001659:Biliary Tract / Q000166:cytology* / Q000648:ultrastructure; D002454:Cell Differentiation; D008099:Liver / Q000166:cytology*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D013234:Stem Cells / Q000502:physiology*; D014746:Vimentin / Q000032:analysis; D000509:alpha-Fetoproteins / Q000032:analysis
chemical_list: D000418:Albumins; D014746:Vimentin; D000509:alpha-Fetoproteins