title: Cholangiocytes derived from induced pluripotent stem cells for disease modeling.
abstract: OBJECTIVE
  Biliary diseases are a significant cause of morbidity and mortality. Challenges in establishing accurate in-vitro methods to model human bile duct diseases and evaluate therapies have contributed to a lack of effective medical treatments. The recent discovery of strategies to reprogram human somatic cells to a state of induced pluripotency has opened up new possibilities for studying both development and disease in a wide variety of human tissues. This review was undertaken to summarize the recent progress made in generating biliary tissue from induced pluripotent stem cells (iPSCs) and the application of this technology to biliary disease modeling.
  
  
  RESULTS
  Several groups have reported defined differentiation protocols that incorporate key signaling cues from normal biliary development to yield cholangiocyte-like cells from wild-type human iPSCs that demonstrate epithelial morphology in two and three-dimensional culture, cholangiocyte markers, biliary gene expression profiles, and functional attributes consistent with biliary epithelium. Key features of Alagille syndrome and polycystic liver disease can be modeled with iPSC-derived cholangiocytes, whereas the use of iPSCs from cystic fibrosis patients has facilitated not only modeling of cystic fibrosis biliary disease but also in-vitro correction of the disorder with pharmacological agents.
  
  
  CONCLUSIONS
  Mature, functional cholangiocytes can be derived from human iPSCs and utilized to model biliary diseases in vitro. These advances should facilitate further research to improve our understanding of the pathophysiology of cholangiopathies and evaluate novel treatments. In the future, this technology will likely form a key element of tissue replacement strategies.
authors.affiliation: aDivision of General Surgery, Toronto General Hospital, University Health Network bDepartment of Surgery, University of Toronto cDivision of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children dDepartment of Pediatrics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Anand
authors.initials: A
authors.lastname: Ghanekar
authors.forename: Binita M
authors.initials: BM
authors.lastname: Kamath
mesh_terms: D001649:Bile Duct Diseases / Q000503:physiopathology; D001652:Bile Ducts / Q000166:cytology* / Q000254:growth & development / Q000502:physiology; D002454:Cell Differentiation; D004847:Epithelial Cells / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D057026:Induced Pluripotent Stem Cells / Q000502:physiology*; D008954:Models, Biological