Human pluripotent stem cell-derived cholangiocytes: current status and future applications

PURPOSE OF REVIEWPluripotent stem cells, such as embryonic stem cells and inducible pluripotent stem (iPS) cells, have high proliferative multipotency for differentiation into mature functional cells that are useful for treatment and basic research on several diseases. Cholangiocytes are differentiated from fetal hepatic progenitor cells (hepatoblasts) and are important for transport of bile acids that are synthesized by mature hepatocytes in the liver. However, the molecular mechanisms of development and function of human cholangiocytes remain unknown. This review mentions the potential of human cholangiocytic culture from pluripotent stem cells to contribute to the analyses of the human bile duct system and diseases. RECENT FINDINGSRecent studies found that human hepatic cholangiocytic cells can be differentiated from human embryonic stem and iPS cells in a suitable culture condition. Cholangiocytic cysts have epithelial cell polarity formed in a three-dimensional cell culture system using extracellular matrices. SUMMARYDisease pathogenesis was elucidated in vitro using differentiated cells from disease-related iPS cells. Using genome-editing enzymes, iPS cells with disease-specific gene mutations can be easily and rapidly established. These disease-related iPS cells and cholangiocytic culture system may be useful for analyses and drug screening of human bile duct diseases.