title: Improved xenogenic hepatocyte implantation into nude mouse liver parenchyma with acute liver failure when followed by repeated anti-Fas antibody (Jo2) treatment.
abstract: Hepatocyte transplantation is a promising therapy for acute liver failure in humans. Recently, we succeeded in inducing various acute and chronic liver failures in nude mice. Engraftment of transplanted xenogeneic rat hepatocytes, visualized in the host liver by anti-MHC class I immunohistochemistry, revealed that liver repopulation was limited, and equivalent in nude mice with and without acute liver failure. In the present study, acute liver failure was induced in nude mice by a single injection of sublethal anti-Fas antibody Jo2, followed 24 h later by rat hepatocyte transplantation and than by a weekly repeated injection of Jo2. Rat hepatocyte engraftment into the recipient liver parenchyma 3 weeks following hepatocyte transplantation was about sevenfold increased when nude mice were subsequently subjected to weekly repeated Jo2 injection. Genomic analysis of these mice showed an overall transcriptome profile of upregulation of cellular cycle blocking transcripts, activation of liver injury inducing IFN-gamma/STAT1 pathway, and circadian transcript signature of antiproliferative cell status compared to mice submitted to hepatocyte transplantation only. The findings of the present study suggest that the induction of cell proliferation blockade in recipient livers could promote sufficient engraftment of transplanted hepatocytes to allow transient or definitive treatment of liver failure in humans.
authors: EA 3921, IFR 133, Faculté de Médecine et de Pharmacie, Besançon, France.
authors: Isabelle
authors: I
authors: Vidal
authors: Nadège
authors: N
authors: Blanchard
authors: Eliane
authors: E
authors: Alexandre
authors: Arnaud
authors: A
authors: Gandillet
authors: Marie-Pierre
authors: MP
authors: Chenard-Neu
authors: Frank
authors: F
authors: Staedtler
authors: Martin
authors: M
authors: Schumacher
authors: Philippe
authors: P
authors: Bachellier
authors: Daniel
authors: D
authors: Jaeck
authors: Huseyin
authors: H
authors: Firat
authors: Bruno
authors: B
authors: Heyd
authors: Lysiane
authors: L
authors: Richert
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology; D049109:Cell Proliferation; D005260:Female; D015870:Gene Expression; D006085:Graft Survival / Q000235:genetics / Q000276:immunology*; D022781:Hepatocytes / Q000637:transplantation*; D007371:Interferon-gamma / Q000378:metabolism; D017114:Liver Failure, Acute / Q000276:immunology / Q000628:therapy*; D008115:Liver Regeneration / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D051381:Rats; D017207:Rats, Sprague-Dawley; D050794:STAT1 Transcription Factor / Q000378:metabolism; D014183:Transplantation, Heterologous; D019014:fas Receptor / Q000037:antagonists & inhibitors / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D050794:STAT1 Transcription Factor; D019014:fas Receptor; D007371:Interferon-gamma