EVIDENCE OF METABOLIC ACTIVITY OF ADULT AND FETAL RAT HEPATOCYTES TRANSPLANTED INTO SOLID SUPPORTS

Abstract

This study was undertaken to assess the metabolic effect of fetal and adult hepatocyte transplantation in the Gunn rat, genetically incapable of bilirubin conjugation. A comparison was made between fetal and adult hepatocytes transplanted into the spleen, and those injected into polytetrafluoroethylene (PTFE) solid supports that had previously been implanted intraperitoneally. Between 4 and 12 weeks after intrasplenic transplantation of adult liver cells, serum bilirubin was significantly decreased when compared with control animals (39.6 +/- 5.6%; P less than 0.01 vs. controls). Intrasplenic transplantation of fetal hepatocytes resulted in a maximal decrease of 33.2 +/- 9.1% at 8 weeks postoperatively (P less than 0.02 vs. controls). Similar declines of serum bilirubin levels were found after transplantation of adult or fetal liver cells into the solid supports. At 12 weeks after transplantation, bilirubin conjugates were detectable in the bile of all animals that underwent intrasplenic hepatocyte transplantation and in 60% of those that underwent the solid support procedure, whereas none could be detected in control animals. Histological evidence of surviving cells was obtained in all but one animal at 12 weeks, and confirmed at 12 months postoperatively. It is concluded that the PTFE solid support technique offers an attractive alternative to the intrasplenic route, and that both fetal and adult hepatocytes, transplanted in either way still exert their conjugating activity after 12 week