Origin of stellate cells from submesothelial cells in a developing human liver

Abstract

Background: The embryonic origin of liver stellate cells is unknown. Methods: We investigated the development of stellate cells in histological sections of human liver of 7–20 weeks gestation, using neural cell adhesion molecule (N‐CAM) to highlight stellate cells by the immunoperoxidase method. Results: We observed a layer of submesothelial cells beneath the liver capsule in the first trimester of gestation, which express N‐CAM and desmin antigens by the immunoperoxidase method but not epithelial‐cadherin, smooth muscle actin or CD34 antigens, unlike hepatocytes and similar to septum transversum mesenchyme. In embryonic liver, stellate cells appeared to grow from pockets of submesothelial cells, with transitional forms observed between the cell types. The submesothelial cells morphologically resemble those described during the rapid growth phase in avian liver, which have been shown to be precursors of stellate cells. There is considerable evidence for epithelial–mesenchymal interactions during development, and we have also found that hepatocytes adjacent to the capsule and around the portal tracts show enhanced expression of β‐catenin in developing liver. These are sites in which stellate cells appeared to be concentrated. Conclusion: We present evidence to suggest that stellate cells originate from submesothelial cells, which possibly derive from the septum transversum.