Abstract
The possibility to reproduce key tissue functions in vitro from induced pluripotent stem cells (iPSCs) is offering an incredible opportunity to gain better insight into biological mechanisms underlying development and disease, and a tool for the rapid screening of drug candidates. This review attempts to summarize recent strategies for specification of iPSCs towards hepatobiliary lineages —hepatocytes and cholangiocytes—and their use as platforms for disease modeling and drug testing. The application of different tissue-engineering methods to promote accurate and reliable readouts is discussed. Space is given to open questions, including to what extent these novel systems can be informative. Potential pathways for improvement are finally suggested.
Highlights
The hepatobiliary system, which includes the liver and the biliary tract, is crucial for several physiological processes
The turning point occurred in 2006, when Yamanaka and Takahashi discovered that it is possible to convert somatic cells into cells with pluripotent features [36]. Their reprogramming strategy was based on retroviral transduction of four transcription factors, namely octamer-binding transcription factor 3/4 (Oct3/4), sex-determining region Y-box 2 (Sox2), krupper-like factor 4 (Klf4), and cellular myelocytomatosis (c-Myc)
What emerges from the literature is that while it is possible to differentiate induced pluripotent stem cells (iPSCs) towards hepatocyte-like cells with the only use of small molecules modulating crucial signaling pathways, cholangiocyte protocols still suffer from the dependence of growth factors, interleukins, and other compounds for both specification and maturation stages
Summary
The hepatobiliary system, which includes the liver and the biliary tract, is crucial for several physiological processes. In experimental and clinical biliary tract injury, and in various types of liver injury, cells with mixed hepatobiliary phenotype arise along the canals of Hering (the anatomic interface between cholangiocytes and hepatocytes), the portal bile duct, and the periportal areas [8,9,10,11]. The development of the induced pluripotent stem cell (iPSC) technology, which allows to convert one cell type into another [36], has created a potentially inexhaustible supply of cells for large-scale toxicity testing and drug screening, and an outstanding source of patient-specific cells for disease modeling Both hepatocytes and cholangiocytes have been generated from iPSCs [37]. We review the current literature around the use of tissue-engineering approaches to improve iPSC specification and maturation towards hepatobiliary lineages
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
