title: The role of HGF on invasive properties and repopulation potential of human fetal hepatic progenitor cells.
abstract: The success of hepatocyte transplantation has been limited by the low efficiency of transplanted cell integration into liver parenchyma. Human fetal hepatic progenitor cells (hepatoblasts) engraft more effectively than adult hepatocytes in mouse livers. However, the signals required for their integration are not yet fully understood. We investigated the role of HGF on the migration and invasive ability of human hepatic progenitors in vitro and in vivo. Hepatoblasts were isolated from the livers of human fetuses between 10 and 12 weeks of gestation. Their invasive ability was assessed in the presence or absence of HGF. These cells were also transplanted into immunodeficient mice and analyzed by immunohistochemistry. In contrast to TNF-alpha, HGF increased the motogenesis and invasiveness of hepatoblasts, but not of human adult hepatocytes, via phosphorylation of extracellular signal-regulated kinase (ERK) 1/2. The invasive ability of human hepatoblasts correlated with the expression and secretion of matrix metalloproteinases (MMPs). Hepatoblasts stimulated with HGF prior transplantation into newborn mice migrated from the portal area into the hepatic parenchyma.
  
  
  CONCLUSIONS
  In contrast to adult hepatocytes, hepatoblasts display invasive ability that can be modulated by HGF in vitro and in vivo.
authors.affiliation: Inserm U972, University Paris-Sud, IFR 69, Hôpital du Kremlin-Bicêtre, Le Kremlin-Bicêtre, France.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Delgado
authors.forename: Valérie
authors.initials: V
authors.lastname: Vanneaux
authors.forename: Julie
authors.initials: J
authors.lastname: Branger
authors.forename: Thomas
authors.initials: T
authors.lastname: Touboul
authors.forename: Loïc
authors.initials: L
authors.lastname: Sentilhes
authors.forename: Sylvie
authors.initials: S
authors.lastname: Mainot
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Lainas
authors.forename: Philippe
authors.initials: P
authors.lastname: Leclerc
authors.forename: Georges
authors.initials: G
authors.lastname: Uzan
authors.forename: Dominique
authors.initials: D
authors.lastname: Mahieu-Caputo
authors.forename: Anne
authors.initials: A
authors.lastname: Weber
mesh_terms: D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D005333:Fetus; D017228:Hepatocyte Growth Factor / Q000494:pharmacology / Q000502:physiology*; D022781:Hepatocytes / Q000637:transplantation*; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010766:Phosphorylation; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D014183:Transplantation, Heterologous
chemical_list: C066855:HGF protein, human; D017228:Hepatocyte Growth Factor; D048052:Mitogen-Activated Protein Kinase 3