title: Repeated transplantation of hepatocytes prevents fulminant hepatitis in a rat model of Wilson's disease.
abstract: The outcome of consecutive hepatocyte transplants was explored in a rat model of Wilson's disease before the onset of fulminant hepatitis without preconditioning regimens. Rats received a high-copper diet in order to induce a rapid induction of liver failure. Sham-operated rats (15/15) developed jaundice and fulminant hepatitis, and they died within 4 weeks of first transplantation. Despite the continuation of a high dietary copper challenge, long-term survival was observed for a notable proportion of the transplanted animals (7/18). All survivors displayed normalized levels of hepatitis-associated serum markers and ceruloplasmin oxidase activity by posttransplant days 50 and 98, respectively. The liver copper concentrations, the liver histology, and the expression of marker genes were significantly restored within 4 months of transplantation in comparison with the control group. The high expression of a copper transporter gene (ATPase Cu++ transporting beta polypeptide) in the livers of the survivors indicated a high rate of repopulation by donor hepatocytes. Our data suggest that repeated cell transplantation can overcome the limitations of a single therapy session in rats with severe hepatic disease by functionally restoring the host liver without preconditioning.
authors.affiliation: Clinic for Transplantation Medicine, Mu¨nster University Clinic, Münster, Germany.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Sauer
authors.forename: Ramsi
authors.initials: R
authors.lastname: Siaj
authors.forename: Sandra
authors.initials: S
authors.lastname: Stöppeler
authors.forename: Ralf
authors.initials: R
authors.lastname: Bahde
authors.forename: Hans-Ullrich
authors.initials: HU
authors.lastname: Spiegel
authors.forename: Gabriele
authors.initials: G
authors.lastname: Köhler
authors.forename: Andree
authors.initials: A
authors.lastname: Zibert
authors.forename: Hartmut H J
authors.initials: HH
authors.lastname: Schmidt
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D003300:Copper; D000073840:Copper-Transporting ATPases; D004195:Disease Models, Animal; D006505:Hepatitis / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D006527:Hepatolenticular Degeneration / Q000139:chemically induced / Q000150:complications / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D009154:Mutation; D051381:Rats; D020318:Rats, Long-Evans; D055647:Rats, Transgenic; D012086:Reoperation; D013997:Time Factors
chemical_list: D015415:Biomarkers; D027682:Cation Transport Proteins; D003300:Copper; D000251:Adenosine Triphosphatases; D000073840:Copper-Transporting ATPases