The hepatic stem cell niche: identification by label-retaining cell assay

Hepatology. 2008 Jun;47(6):1994-2002. doi: 10.1002/hep.22218.

Abstract

Label retention assays remain the state-of-the-art approach to identify the location of intraorgan epithelial stem cell niches, in situ and in vivo. They are commonly used in organs with rapid cell turnover but have not been applied to the liver, where cell turnover is very slow. We used a sublethal dose of acetaminophen administered coincident with bromodeoxyuridine to load possible hepatic stem cells in mice with label and then administered a second, sublethal chase of acetaminophen to accomplish "washout" of label from transit amplifying cell populations.

Conclusion: Four possible hepatic stem cell niches are identified by this approach: the canal of Hering (proximal biliary tree), intralobular bile ducts, periductal "null" mononuclear cells, and peribiliary hepatocytes. These results confirm several different and often contradictory lines of investigation regarding the intrahepatic location of stem/progenitor cells and suggest that the liver has a multi-tiered, flexible system of regeneration rather than a single stem/progenitor cell location.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetaminophen / pharmacology
  • Analgesics, Non-Narcotic / pharmacology
  • Animals
  • Bile Ducts / cytology*
  • Bile Ducts / drug effects
  • Bile Ducts / metabolism
  • Bromodeoxyuridine / metabolism
  • Cell Differentiation / physiology
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Hepatocytes / cytology*
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism
  • Liver / cytology*
  • Liver / drug effects
  • Liver / metabolism
  • Liver Regeneration / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Stem Cells / cytology*
  • Stem Cells / drug effects
  • Stem Cells / metabolism

Substances

  • Analgesics, Non-Narcotic
  • Acetaminophen
  • Bromodeoxyuridine