title: Mycophenolate mofetil and sirolimus in hepatocyte transplantation in an experimental model of toxic acute liver failure.
abstract: BACKGROUND
  Hepatocyte transplantation is proposed as a solution for liver failure. The allotransplantation of hepatocytes has been studied extensively, however, graft rejection remains a major problem. The aim of the present study was to evaluate the immunosuppressive activity of mycophenolate mofetil (MMF), sirolimus, and their combination in an experimental model of hepatocyte allotransplantation in rats with acute liver failure.
  
  
  METHODS
  Five male Wistar rats were used as hepatocyte donors and 60 male Lewis rats as recipients. The recipients were divided into five groups of 12 animals each. Group 1: no treatment. Group 2: cyclosporine. Group 3: sirolimus. Group 4: MMF. Group 5: MMF and sirolimus. All surviving animals were preserved for 15 days. For the induction of acute liver failure the recipients were injected with N-dimethyl-nitrosamine 24 hr before transplantation. The isolated hepatocytes were transplanted intrasplenically.
  
  
  RESULTS
  Analysis of the results showed a statistically significant prolongation of animal survival for groups 3, 4, and 5. More animals in group 5 survived than those in groups 3 and 4, although the difference was not statistically significant. Transplant hepatocyte survival was significantly better in groups 3, 4, and 5. Hepatocytes transplanted in the spleen of animals of group 5 showed better survival compared with those of groups 3 and 4.
  
  
  CONCLUSIONS
  Use of MMF and sirolimus, as monotherapy or in combination, is both effective and safe as immunosuppressive treatment in hepatocyte transplantation, as was proven in this experimental protocol.
authors.affiliation: University of Athens , Athens , Greece .
authors.forename: Ioannis
authors.initials: I
authors.lastname: Loukopoulos
authors.forename: Ioannis
authors.initials: I
authors.lastname: Sfiniadakis
authors.forename: Andrew
authors.initials: A
authors.lastname: Pillai
authors.forename: Manousos
authors.initials: M
authors.lastname: Konstantoulakis
authors.forename: Georgios
authors.initials: G
authors.lastname: Androulakis
authors.forename: Vassilios
authors.initials: V
authors.lastname: Bonatsos
authors.forename: Georgios
authors.initials: G
authors.lastname: Zografos
authors.forename: Apostolos
authors.initials: A
authors.lastname: Papalois
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006084:Graft Rejection / Q000517:prevention & control; D022781:Hepatocytes / Q000637:transplantation*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D017114:Liver Failure, Acute / Q000401:mortality / Q000601:surgery*; D008297:Male; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011917:Rats, Inbred Lew; D017208:Rats, Wistar; D020123:Sirolimus / Q000627:therapeutic use*; D013154:Spleen / Q000473:pathology / Q000601:surgery
chemical_list: D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D020123:Sirolimus
keywords: experimental; hepatocyte; model; mycophenolate mofetil; sirolimus; transplantation