title: Hepatic regeneration in the isolated perfused rat liver followed by liver transplantation.
abstract: Controlling the S phase of the hepatocyte cell cycle would be of considerable help for stable retroviral foreign gene transfer. The aim of this article is to study hepatocyte regeneration during S phase in isolated, perfused rat liver followed by liver transplantation. Normal livers (G I: n = 7) were perfused with blood from normal rats for 6.1+/-0.3 hours. Regenerating livers (G II; n = 7) obtained 18 hours after partial hepatectomy were perfused for 6.0+/-0.3 hours with blood from rats partially hepatectomized 18 hours before. Regenerating livers (G III; n = 7) obtained 22 hours after partial hepatectomy were perfused for 2.4+/-0.1 hours with blood from normal rats. In the normothermal perfusion system, a bolus of 25 mg of 5-bromo-2'-deoxyuridine (BrdU) was added to the perfusate. Liver biopsies were taken at the end of each experiment. In group II, a biopsy was also taken 1 hour after BrdU introduction. At the end of each experiment, livers were orthotopically transplanted. The percentage of BrdU positive hepatocyte nuclei was 0.2% in G I; 14.8% and 38.4% after 1 hour and 6.1 hours, respectively, in G II; and 46.5% after 2.4 hours in G III. In G I, five rats died at day 1, 5, 6, 7, and 48 and two rats were still alive after 17 months. In G II, all the rats died before day five. In G III, two rats died at day one, one at day six, and four were still alive after 12 months. This study shows that, after 6 hours of normothermal perfusion, organ viability allows successful liver transplantation and that rat hepatocyte regeneration during cell cycle S phase in isolated normothermal conditions progresses in a similar way-quantity and timing-to liver regeneration found in vivo after partial hepatectomy.
authors.affiliation: Laboratoire de Recherche Chirurgical, Faculté de Médecine Cochin-Port Royal, Université Paris V, France.
authors.forename: J L
authors.initials: JL
authors.lastname: De Godoy
authors.forename: M
authors.initials: M
authors.lastname: Fabre
authors.forename: B
authors.initials: B
authors.lastname: Cherruau
authors.forename: M
authors.initials: M
authors.lastname: McIntyre
authors.forename: O
authors.initials: O
authors.lastname: Soubrane
authors.forename: D
authors.initials: D
authors.lastname: Houssin
authors.forename: J E
authors.initials: JE
authors.lastname: Cardoso
mesh_terms: D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002453:Cell Cycle; D006498:Hepatectomy; D008115:Liver Regeneration; D016031:Liver Transplantation; D008297:Male; D010477:Perfusion; D051381:Rats; D011917:Rats, Inbred Lew
chemical_list: D001973:Bromodeoxyuridine