Differentiation and characterization of cholangiocytes from human pluripotent stem cells.

Over the last years, human embryonic and so-called induced pluripotent stem cells (made from skin or other cells) can be differentiated to liver cells (hepatocytes). These cells resemble closely primary liver cells, however further optimization of the protocol is necessary. Besides hepatocytes, the liver also contains bile duct cells (cholangiocytes). These cells have been studied less intensively than hepatocytes because they were previously considered as simple lining cells of the bile ducts. Now there is increasing evidence from animal models that these cells are crucial in many different biliary diseases, both congenital as acquired.

In this project I will differentiate human stem cells to bipotential cells that can become hepatocytes or cholangiocytes; these cells will then be differentiated to cholangiocytes and characterized. Optimization using growth factors and co-culture with other cell types will be tested. I will also investigate which human genes are necessary for cholangiocyte differentiation by increasing or decreasing their expression and determine the effect on cholangiocyte differentiation. In a last part, stem cells will be created from patients with polycystic liver disease and congenital absence of bile ducts (biliary atresia). This should allow us to investigate the pathophysiology behind this disease and may lead to diagnosis of new genetic defects underlying bile duct diseases.