Multiple intrasplenic hepatocyte transplantations in the dalmatian dog

Background. Hepatocyte transplantation is an attractive potential treatment for liver-based inborn errors of metabolism and for fulminant hepatic fail ure. Dalmatian dogs have a metabolic error that results in hyperuricosuria. This report focuses on the effect of multiple, sequential intrasplenic tra nsplants of fresh and cryopreserved hepatocytes in dalmatians. Methods. Dalmatians underwent intrasplenic hepatocyte transplantation with hepatocytes taken from healthy mongrels. Dalmatian urinary uric acid excret ion was measured preoperatively and this served as the control value. Three hepatocyte transplantations were performed at 30-day intervals-the first w ith freshly isolated cells, and both the second and the third with cryopres erved hepatocytes from the same donor Urinary uric acid excretion was measu red postoperatively twice pw week. Results, The urinary uric acid excretion decreased an average of 54% after the first hepatocyte transplantation. The effect was transient and lasted a n average of 22 days (range, 19-50 days). Subsequent intrasplenic hepatocyt e transplantation with cryopreserved hepatocytes resulted in similar decrea ses In urinary uric acid excretion. Each transplant resulted in a significa nt decrease in urinary uric acid excretion when compared with baseline valu es (P = <.001). Conclusions. Sequential intrasplenic hepatocyte transplantation is feasible in this model. This method provided a significant, but transient, correcti on in urinary uric acid excretion that was similar with either fresh or cry opreserved hepatocytes. A substantial biologic effect provided by cryoprese rved hepatocytes has important implications in clinical hepatocyte transpla ntation.