Liver gene expression and increase in albumin synthesis by fetal hepatocytes transplanted into analbuminemic rats

This report describes the evolution of hepatocytes isolated from 21-day fet uses and transplanted into spleens of Nagase analbuminemic rats which have negligible serum albumin levels due to a mutation affecting albumin mRNA pr ocessing. Albumin and alpha-fetoprotein expression, in addition to other pa rameters related to cellular proliferation status (thymidine kinase and pro liferating cell nuclear antigen expression) were studied as indicative of t he behavior and evolution of the cells. In recipient rats, only a few clust ers of hepatocytes could be observed in the red pulp of the spleen 24 h aft er transplantation. The fetal hepatocytes migrated to the liver and could b e seen in portal branches immediately after transplantation. Fifteen days l ater, albumin mRNA was detected in recipient livers and was expressed throu ghout the entire 3-month study. Alpha-fetoprotein was not detected. Cell pr oliferation was not relevant, although 3 months after transplantation, the proliferation rates appeared to show a tendency to increase. These data dem onstrate that fetal hepatocytes transplanted into spleen migrate to liver, settle there and acquire an adult phenotype free of malignant transformatio n. Our study is a first step towards the thorough understanding of fetal he patocyte transplantation. The next steps will involve in-depth studies of t he possibilities of genetic manipulation to achieve a high degree of repopu lation/expression, employing the least possible number of donor cells, and of how the cells reach the liver parenchyma, overcoming the endothelial bar rier. (C) 2000 Elsevier Science Inc. All rights reserved.