Of streaming hepatocytes and meandering sinusoids

Abstract

The fate of normal hepatocytes in adult rat liver was studied after genetic labelling using the Escherichia coli β-galactosidase gene coupled to a nuclear localisation signal. The marker gene was introduced by direct in vivo retroviral-mediated gene transfer into hepatocytes 24 h after partial hepatectomy. Analysis of β-galactosidase expression in the liver at various times after gene transfer revealed that labelled hepatocytes were distributed throughout the entire lobule with a predominance in the periportal and mediolobular regions. Long-term experiments demonstrated that division of hepatocytes did occur as was revealed by the increasing number of β-galactosidase-positive cells in isolated clusters. There was no evidence for the participation of stem cells in this process. Moreover, we found that after more than one year, the pattern of distribution of positive cells within the lobule was not modified. This suggests that hepatocytes do not migrate from the portal space to the perivenous region, as has been previously hypothesised.