Developmental Expression of Cytochrome P450S within Intrasplenically Transplanted Fetal Hepatocytes from Spontaneously Hypertensive Rats

Abstract

Fetal hepatocytes were harvested at 20 days of gestation from spontaneously hypertensive rats (SHR) and then transplanted into recipient adult SHR spleens. Morphological examination of the recipient spleens revealed that after 4 wk, large masses of hepatocytes were present in the red pulp with apparent cord-like structures. Of major significance was the fact that hepatocyte transplanted spleens were able to express several families of cytochrome P450 (cyto P450) proteins 2-6 wk after transplantation. Thus, the transplanted hepatocyte tissue appeared to grow and develop a cyto P450 metabolic system. Immunochemical determinations revealed that cytos P450 IA1, P450 IIB1, P450 p, P450 HLp, and P450 LAω were over detected without any prior induction. None of the cyto P450s could be detected in control nontransplanted spleens, however all were detected in fetal hepatocyte microsomes before transplantation. All were intensely expressed 6 wk after transplantation, however P450 IA1 and P450 IIB1 did not appear to be expressed by 2 wk after transplantation. These results demonstrate that fetal hepatocytes can be successfully transplanted to the spleens of recipient hosts, and that the fetal hepatocytes appear to grow and develop functional cyto P450 metabolizing systems. Therefore, transplantation of fetal hepatocytes to splenic tissue represents a unique in vivo system of extra hepatic metabolizing tissue.