Expression and Inducibility of Cytochrome P450 Iiia Family within Intrasplenically Transplanted Fetal Hepatocytes

Abstract

With the development of transplantation of hepatocytes into the spleen, interest has focused on the metabolic changes associated with hepatocyte proliferation. As these changes are important for drug metabolism in hepatocytes, we examined the expression and inducibility of the cytochrome P450 IIIA family within transplanted hepatocytes. Fetal hepatocytes were harvested at 20 days of gestation from spontaneously hypertensive rats (SHRs) and transplanted into recipient adult SHR spleens. Microscopic examination of the recipient spleens 4 and 10 wk after transplantation revealed masses of hepatocytes with cordlike structures in the red pulp. Proliferating hepatocytes were detected with a bromodeoxyuridine (BrdU) immunohistochemical stain. Immunochemical studies detected cytochromes (cytos) P450 p and P450 HLp in fetal hepatocytes before transplantation without prior induction. And although these cytos were not detected by 10 wk after transplantation, they were induced with dexamethasone. These results demonstrated that fetal hepatocytes can be transplanted successfully into recipient spleens and suggested that fetal hepatocytes grow in the spleen, similar to the adult hepatocyte response.