TY - JOUR
TI - Mycophenolate mofetil and sirolimus in hepatocyte transplantation in an experimental model of toxic acute liver failure
AU - Loukopoulos, I.
AU - Sfiniadakis, I.
AU - Pillai, A.
AU - Konstantoulakis, M.
AU - Androulakis, G.
AU - Bonatsos, V.
AU - Zografos, G.
AU - Papalois, A.
JO - Journal of Investigative Surgery
PY - 2014
VL - 27
TODO - 4
SP - 205-213
PB - LIBRAPHARM/INFORMA HEALTHCARE
SN - 0894-1939, 1521-0553
TODO - 10.3109/08941939.2013.879967
TODO - alkaline phosphatase;  bilirubin;  creatinine;  cyclosporin;  dimethylnitrosamine;  mycophenolic acid 2 morpholinoethyl ester;  rapamycin;  immunosuppressive agent;  mycophenolic acid;  mycophenolic acid 2 morpholinoethyl ester;  rapamycin, acute liver failure;  allotransplantation;  animal cell;  animal experiment;  animal model;  animal tissue;  article;  controlled study;  experimental study;  graft recipient;  hepatocyte transplantation;  immunosuppressive treatment;  liver cell;  male;  nonhuman;  priority journal;  rat;  spleen;  survival;  analogs and derivatives;  animal;  disease model;  evaluation study;  graft rejection;  Lewis rat;  Liver Failure, Acute;  mortality;  pathology;  transplantation;  Wistar rat, Animals;  Disease Models, Animal;  Graft Rejection;  Hepatocytes;  Immunosuppressive Agents;  Liver Failure, Acute;  Male;  Mycophenolic Acid;  Rats, Inbred Lew;  Rats, Wistar;  Sirolimus;  Spleen
TODO - 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. © 2014 Informa Healthcare USA, Inc.
ER -