Immunohistochemical study of the phenotypic change of the mesenchymal cells during portal tract maturation in normal and fibrous (ductal plate malformation) fetal liver

At the early steps of the portal tract maturation, portal mesenchymal cells expressed only ASMA. During the maturation process, these cells were found condensed around the biliary and vascular structures. At the end of maturation process, only cells around vessels expressed ASMA and cells of the artery tunica media also expressed h-caldesmon. In contrast, ASMA positive cells persisted around the abnormal biliary ducts in fibrous livers.As in adult liver, there is a phenotypic heterogeneity of the mesenchymal cells during fetal liver development. During portal tract maturation, myofibroblastic cells disappear in normal development but persist in fibrosis following ductal plate malformation.In the liver, different fibrocompetent cells have been described in accordance with their topography, their morphology and their main functions: portal fibroblasts and vascular smooth muscle cells in the portal tract; hepatic stellate cells (HSC) and "second layer cells" around the centrolobular veins in lobular area (review in Guyot et al [1]). The heterogeneity of these fibrocompetent cells is characterised by the expression of different markers. For example, quiescent HSC express cellular retinol-binding protein-1 (CRBP-1) but not alpha-smooth muscle actin (ASMA) or h-caldesmon [2-5]. Vascular smooth muscle cells expressed ASMA and h-caldesmon [6]. Finally, portal fibroblasts expressed neither ASMA nor CRBP-1, but expressed vimentin [3,4]. Myofibroblasts are absent in the normal liver but, during liver fibrosis, these cells can acquire a myofibroblastic phenotype, notably by the expression of ASMA [1,7].The phenotypic evolution of mesenchymal cells during the fetal human liver development has not been studied with the markers discussed above. The mesenchymal cells derived from the stroma of the septum transversum which is invaded by epithelial cell clusters from hepatic diverticulum during the 4th week of development (WD) [8]. The lobulation of the fetal liver begin near the liv