Mycophenolate mofetil and sirolimus in hepatocyte transplantation in an experimental model of toxic acute liver failure

J Invest Surg. 2014 Aug;27(4):205-13. doi: 10.3109/08941939.2013.879967. Epub 2014 Feb 24.


Introduction: 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.

Materials and 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.

Conclusion: 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.

Keywords: experimental; hepatocyte; model; mycophenolate mofetil; sirolimus; transplantation.

Publication types

  • Evaluation Study

MeSH terms

  • Animals
  • Disease Models, Animal
  • Graft Rejection / prevention & control
  • Hepatocytes / transplantation*
  • Immunosuppressive Agents / therapeutic use*
  • Liver Failure, Acute / mortality
  • Liver Failure, Acute / surgery*
  • Male
  • Mycophenolic Acid / analogs & derivatives*
  • Mycophenolic Acid / therapeutic use
  • Rats, Inbred Lew
  • Rats, Wistar
  • Sirolimus / therapeutic use*
  • Spleen / pathology
  • Spleen / surgery


  • Immunosuppressive Agents
  • Mycophenolic Acid
  • Sirolimus