The role of HGF on invasive properties and repopulation potential of human fetal hepatic progenitor cells.
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.
Delgado
Jean-Paul
JP
Inserm U972, University Paris-Sud, IFR 69, Hôpital du Kremlin-Bicêtre, Le Kremlin-Bicêtre, France.
Vanneaux
Valérie
V
Branger
Julie
J
Touboul
Thomas
T
Sentilhes
Loïc
L
Mainot
Sylvie
S
Lainas
Panagiotis
P
Leclerc
Philippe
P
Uzan
Georges
G
Mahieu-Caputo
Dominique
D
Weber
Anne
A
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
C066855:HGF protein, human; D017228:Hepatocyte Growth Factor; D048052:Mitogen-Activated Protein Kinase 3