Dosage Depended Acetaminophen-Induced Acute Liver Failure in Pigs

Abstract

The shortage of organ donors has impeded the development of human hepatocyte transplantation. Immortalized hepatocytes could provide an unlimited supply of transplantable cells. To determine whether immortalized hepatocytes could provide global metabolic support in end-stage liver disease, 42 immortalized rat hepatocytes clones were developed by transduction with Artifi cal Human Chromosome (HAC) encoding the Simian virus 40 T antigen (SV40Tag) . The SV40Tag sequence and a suicide gene, herpes simplex virus thymidine kinase (HSV-tk), were fl anked by FRT sequences so that they could be excised by FRT recombination. When transplanted into the spleen of retrosin treated non albumin rats with 2/3 hepatectomy with FK506 (R-NARs), immortalized hepatocyte clones prevented the development of albumin. The protection was reversed by Ganciclovir treatment, which kills HSV-tk expressing cells. Three experimental groups were used for alnumin analysis: (G1) non albumin rats with 2/3 hepatectomy only (R-NARs) (n=4); (G2) R-NARs and intrasplenic transplantation of 3x107 primary hepatocytes (pHTx) (n=4); (G3) R-NARs and intrasplenic transplantation of 3x107 immortalized hepatocytes (iHTx) (n=4) All HTx group(G2-3) were made albumin but immortalized hepatocytes were not signifi cantly elevated albumin level conpared with primary hepatocyte. Immortalized hepatocytes group were not shown up tumor after one month HTx. The metabolic support provided by the immortalized cells not equalled that observed after transplantation of primary rat hepatocytes, but in afuthur can be engineered to contain safeguards that could make them clinically useful.