Liver repopulation by Bcl-x(L) transgenic hepatocytes.
Liver repopulation could constitute a potential therapeutic alternative to liver transplantation in the future. Therefore, the development of liver repopulation strategies is of major interest. We have previously reported that Bcl-2-expressing hepatocytes are resistant to Fas-mediated apoptosis and that these hepatocytes, when transplanted into the spleen, are able to repopulate the liver of normal mice submitted to Fas-mediated apoptosis. We now show that Bcl-x(L)-overexpressing hepatocytes are able to repopulate up to 10% of a normal mouse liver treated with successive injections of anti-Fas antibody. We show that a twofold overexpression of Bcl-x(L) is sufficient to confer a selective advantage to hepatocytes submitted to anti-Fas antibody. Moreover, repopulation percentages obtained here were comparable to those obtained when Bcl-2 hepatocytes were transplanted, suggesting that both proteins are equivalent in conferring a selective advantage to hepatocytes submitted to anti-Fas antibody.
Mitchell
Claudia
C
Department of Genetics, Development and Molecular Pathology, Institut Cochin de Génétique Moléculaire, Paris, France.
Mallet
Vincent O
VO
Guidotti
Jacques E
JE
Goulenok
Cyril
C
Kahn
Axel
A
Gilgenkrantz
Hélène
H
D000818:Animals; D030801:Animals, Genetically Modified / Q000235:genetics; D000906:Antibodies / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology; D022781:Hepatocytes / Q000166:cytology* / Q000502:physiology*; D008099:Liver / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D008115:Liver Regeneration / Q000502:physiology*; D051379:Mice; D008808:Mice, Inbred CBA; D008815:Mice, Inbred Strains; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D051020:bcl-X Protein; D019014:fas Receptor / Q000276:immunology / Q000502:physiology
D000906:Antibodies; C494812:Bcl2l1 protein, mouse; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; D019014:fas Receptor