Immunohystochemical markers of stem/progenitor cells in the fetal human liver

The documentation and the characterization of human stem/progenitor cells of the liver is interesting subject of the current scientific literature. Stem/progenitor cells are a heterogenus population characterized by a range of morphological and immunohistochemical features from bile duct cells to hepatocytes. They are typically characterized by the self-renewal ability able to differentiate into diverse lineage after injury or damage.. This study evaluated the immunohistochemical expression of different type of cytokeratins (CK7, CK14 and CK19) at different gestational ages in order to identify stem/progenitor in fetal human liver. Objectives: The aim of this study was to identify the stem/progenitor cell markers, by immunohistochemistry, in order to highlight the immunoreactivity of CK7, CK14 and CK19 in human liver progenitor cells at different gestational ages. Material and Methods: Liver samples were obtained from 14 fetal liver from 7 to 38 weeks of gestation. Liver samples were formalin-fixed routinely processed and stained with with H&E for histology. Section were also immunostained with the following antibodies: anti-CK7, anti-CK14 and anti-CK19. Results: Cytokeratin 7 (CK7): From 7 to 12 weeks of gestation, the positivity for CK7 is evident in the cytoplasm of progenitor cells of hepatocytes. From 15 weeks to 19 weeks, its immunoreactivity is absent. At about 27 weeks up to 38 weeks, we have a moderate positivity than before. The bile ducts in the first 7 weeks of gestation are absent. From 15 weeks onwards, we have a strong positivity of CK7 in ductal cells, remaining until late gestational age. The positivity of CK7 in the bile ducts is cytoplasmic and perinuclear. Cytokeratin 14 (CK14): From 7 weeks to 12 weeks, a cytoplasmic positivity, mainly perinuclear, is present in the cytoplasm of progenitor cells. From 15 weeks to 19 weeks, no immunoreactivity was found in hepatoblasts. From 27 weeks up to 38 weeks, there is a positive recovery. On the other hand, there is no positive effect during the development of the ductal system. Cytokeratin 19 (CK19): From 7 to 12 weeks of gestation, we have an intense cytoplasmic positivity homogeneously spread at the level of progenitor cells. At 15 weeks it is more light and focal and then negativize and start again from 27 weeks. Like CK7, also the CK19 is intensely expressed in the bile ducts from 15 weeks and then maintained until the 38th gestational age studied. Conclusion: Immunohistochemistry with monoclonal anti-cytokeratin antibodies has revelated previously the presence of cytokeratins in embryonic and early fetal hapatocytes. With the differentiation of bile ducts at about the 10th week, cytokeratin, particulary CK19, disappears from liver cells but remains in bile duct cells. This study shows that the immunoreactivity of the analyzed cytokeratins, in particular CK7 and CK19, is well evident from the first weeks of gestation and is maintained even in late age.