Wholesale hepatocytic differentiation in the rat from ductular oval cells, the progeny of biliary stem cells

Malcolm Alison, Matthew Golding, El Nasir Lalani, Peter Nagy, Snorri Thorgeirsson, Catherine Sarraf

Research output: Contribution to journalArticle

107 Citations (Scopus)

Abstract

Background/Aims: 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 α-foetoprotein. Expression of albumin and α-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 α-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.

Original languageEnglish
Pages (from-to)343-352
Number of pages10
JournalJournal of Hepatology
Volume26
Issue number2
DOIs
Publication statusPublished - Feb 1997

Keywords

  • acetylaminofluorene
  • albumin
  • cytokeratins
  • liver regeneration
  • oval cells
  • vimentin
  • α-foetoprotien

ASJC Scopus subject areas

  • Hepatology

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