As for whole organ transplantation, immunosuppressive drugs are necessary to prevent rejection of hepatocytes after transplantation. The rejection of allogeneic hepatocytes delivered via portal vein was T-cell mediated. It could effectively be avoided by Cyclosporine A treatment. In addition, Cyclosporine A elevated the integration of donor hepatocytes into the recipient liver parenchyma by disturbing the liver endothelium. Mesenchymal stem cells (MSC) differentiated into “hepatocyte-like” cells were used instead of primary hepatocytes for transplantation to prevent acute and chronic liver failure. Regarding their protective features on the liver parenchyma, mesenchymal stem cell-derived “hepatocyte-like” cells seem to be a feasible therapeutic alternative to hepatocyte transplantation. Thus, porcine “hepatocyte-like” cells were generated from bone marrow as well as from subcutaneous/visceral adipose tissue MSC to make these cell sources available for preclinical large animal studies.