CORRECTION OF AN INBORN ERROR OF METABOLISM BY INTRAPORTAL HEPATOCYTETRANSPLANTATION IN A DOG-MODEL

The aims of this study were (1) to assess portal hemodynamics during i ntraportal hepatocyte transplantation (HTX) in dogs, (2) to evaluate a new method for the detection of transplanted hepatocytes using 5-brom o-2'-deoxyuridine (BrdU) incorporation, and (3) to determine the metab olic effects of HTX on an inborn error of the purine metabolism in dal matian dogs. HTX was performed by intraportal infusion of freshly isol ated allogeneic beagle hepatocytes. Portal Bow and pressure were monit ored continuously during HTX. For the detection experiments, beagles r eceived hepatocytes that had been exposed to BrdU during regeneration of the donor liver, induced by partial hepatectomy. For metabolic stud ies, dalmatian dogs were used as recipients. Repetitive HTX was perfor med, As judged by the portal hemodynamics, the number of hepatocytes t hat could be infused safely varied from 5x10(8) to 8x10(8) in beagles, to 1x10(9) in dalmatians. Transaminase levels showed a 5- to 6-fold i ncrease (P=0.05) after HTX, but normalized within 3 weeks. BrdU-positi ve cells were identified in the recipient livers 2 weeks after HTX and 5-10% of the total amount of transplanted hepatocytes was retrieved. A significant (P=0.05) decrease in serum uric acid was demonstrated af ter repeated HTX in dalmatians. In conclusion, (1) intraportal HTX is feasible, but portal. hypertension limits the maximum amount of hepato cytes that can be infused in one HTX; (2) BrdU labeling is an attracti ve method for the detection of transplanted hepatocytes In the recipie nt liver; and (3) after two consecutive hepatocyte transplantations, a temporary correction of the purine metabolism was accomplished in the dalmatian dog.