title: Limited contribution of cells of intact extrahepatic tissue origin to hepatocyte regeneration in transplanted rat liver.
abstract: BACKGROUND
  It is now well established that various adult somatic tissues harbor multipotent stem cells that can differentiate into a broad variety of cell types of all three germ layer origins. It remains controversial, however, whether they are a reservoir of cells utilized for emergent tissue repair or simply a vestige of evolution and, if the former is the case, to what extent they can potentially contribute to reconstitution of a specific organ. To get an insight in such a direction, we examined the extent of contribution of naive intact cells of extrahepatic origin to hepatocyte reconstitution in the transplanted liver with or without injury in the rat.
  
  
  METHODS
  Liver from wild-type donor rats was transplanted to green fluorescent protein (GFP)-transgenic rats, and GFP-positive hepatocytes were examined with or without liver injury.
  
  
  RESULTS
  The proportion of GFP-positive hepatocytes in the transplanted noninjured liver linearly increased by 0.0048% per week, that is, approximately 5 x 10(3) hepatocytes of extrahepatic origin were generated per day. Liver injury induced by treatment with 2-acetylaminofluorene and CCl4 or the additional application of hepatocyte growth factor did not further increase the percentage of GFP-positive hepatocytes.
  
  
  CONCLUSIONS
  The present results indicate that cells derived from nonmanipulated extrahepatic tissues appreciably contribute, though limitedly, to hepatocyte reconstitution in the liver of the rat.
authors.affiliation: Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Tomiyama
authors.forename: Masahiro
authors.initials: M
authors.lastname: Miyazaki
authors.forename: Masataka
authors.initials: M
authors.lastname: Nukui
authors.forename: Mikiro
authors.initials: M
authors.lastname: Takaishi
authors.forename: Atsunori
authors.initials: A
authors.lastname: Nakao
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Shimizu
authors.forename: Nam-ho
authors.initials: NH
authors.lastname: Huh
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000032:analysis / Q000235:genetics*; D022781:Hepatocytes / Q000166:cytology / Q000502:physiology*; D007150:Immunohistochemistry; D008115:Liver Regeneration; D016031:Liver Transplantation / Q000502:physiology*; D023421:Models, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D049452:Green Fluorescent Proteins