The lab of Gianfranco Alpini, PhD has demonstrated that cholangiocytes are morphologically, phenotypically and functionally heterogeneous. The research team was the first to isolate pure cholangiocytes from normal and diseased rat and mice livers, and continually provides isolated cholangiocytes to other groups worldwide that are interested in studying the pathophysiology of these cells.
The Alpini Lab has developed the technique that allows for the isolation of distinct subpopulations of small, medium, and large cholangiocytes from the liver. The group demonstrated that these cholangiocyte subpopulations differ in their secretory activity and proliferative/apoptotic responses to biliary injury induced by cholestasis/toxins.
The Alpini Lab also demonstrated that small cholangiocytes are less differentiated and function through Ca2+-dependent signaling, whereas larger cholangiocytes are more differentiated/senescent and function through activation of cAMP signaling. Also, small cholangiocytes contain a progenitor cell subpopulation that may be important in liver repair during damage of large ones, the more senescent cholangiocytes.
These findings also stimulated numerous research groups to consider the evaluation of the potential stem cell-like properties of small cholangiocytes. The discovery of cholangiocyte heterogeneity has important implications for the advancement of the field since human biliary disorders (such as PSC and PBC) are characterized by proliferation/damage restricted to specific/heterogeneous bile ducts of different sizes.