Further observations on the survival, proliferation and function of ectopically implanted syngeneic and allogeneic liver cells in rat spleen

To investigate further the feasibility of hepatocyte transplantation for treating inborn errors of metabolism, we have studied different techniques for transplanting hepatocytes, and assessing growth and function in syngeneic rats. We also investigated whether short-term immunosuppression might permit long-term graft survival. Whilst isolated hepatocytes in the spleen survived long-term, liver fragments did not. Quantitative histology on serial sections provided a measure of cell growth, but with substantial animal-to-animal variation after injection of aliquots from the same preparation. Activity of carbamoyl phosphate synthetase 1 (CPS) of liver cells within the spleen was demonstrable 12 months after implantation, but in rapidly growing liver there was no fixed relationship between cell number and CPS activity, thus mass of implanted hepatocytes could not be calculated from enzymatic activity. Although administration of cyclosporin A prevented rejection of allogeneic liver cells in the spleen (donor hepatocytes from DA rats, implanted into spleens of August rat recipients) for a month, no liver cells were identified 5 weeks after cessation of immunosuppression.