Abstract
The inbred, homozygous Gunn rat exhibits unconjugated hyperbilirubinemia due to a hereditary absolute deficiency of bilirubin UDP-glucuronyltransferase activity. The mechanism of action of hepatocyte transplantation (HTX) in the treatment of enzyme deficiency has been investigated in this study. Gunn rats underwent HTX by the injection of isolated hepatocytes from a nondeficient donor rat (Wistar) into the spleen. A transient, statistically significant decrease in total plasma bilirubin (TB) levels was observed. Gunn rats receiving Gunn hepatocytes did not show such a decrease. Histological examination 2–3 months post-HTX of the recipient spleens showed the absence of grafted hepatocytes in the first group and graft survival in the second. Bile specimens from sublethal irradiated Gunn rats, collected 6 days after HTX with viable Wistar hepatocytes, all contained bilirubin mono- and diglucuronides. Control groups consisting of Gunn rats receiving nonviable Wistar hepatocytes or Gunn hepatocytes, and sham-operated Gunn rats did not excrete bilirubin glucuronides in bile. It was also demonstrated that bilirubin UDP-glucuronyltransferase activity, which appeared in Gunn rats after HTX with Wistar hepatocytes, was only transient. It is concluded that the decrease of TB in the Gunn rat after HTX with nondeficient hepatocytes is explained by the appearance of the enzyme, which was absent in the recipient animal. Viable, nondeficient hepatocytes are required for the elicited bilirubin conjugation. Rejection of the transplanted hepatocytes abolishes this effect.
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