Bioengineered bile ducts recapitulate key cholangiocyte functions

Investigation of diseases of the bile duct system and identification of potential therapeutic targets are hampered by the lack of tractable in vitro systems to model cholangiocyte biology. Here, we show a step-wise method for the differentiation of murine Lgr5+ liver stem cells (organoids) into chol...

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Bibliographic Details
Published in:Biofabrication 2018-06, Vol.10 (3), p.034103-034103
Main Authors: Chen, Chen, Jochems, Paulus G M, Salz, Lucia, Schneeberger, Kerstin, Penning, Louis C, van de Graaf, Stan F J, Beuers, Ulrich, Clevers, Hans, Geijsen, Niels, Masereeuw, Rosalinde, Spee, Bart
Format: Article
Language:English
Subjects:
Animals
bile acid transport
Bile Acids and Salts - metabolism
Bile Ducts - cytology
Bile Ducts - physiology
bioengineered bile duct
Bioengineering
Cell Differentiation
cholangiocyte
Humans
Liver - cytology
Liver - physiology
liver organoid
Mice
Organoids - cytology
Organoids - physiology
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Summary:Investigation of diseases of the bile duct system and identification of potential therapeutic targets are hampered by the lack of tractable in vitro systems to model cholangiocyte biology. Here, we show a step-wise method for the differentiation of murine Lgr5+ liver stem cells (organoids) into cholangiocyte-like cells (CLCs) using a combination of growth factors and extracellular matrix components. Organoid-derived CLCs display key properties of primary cholangiocytes, such as expressing cholangiocyte markers, forming primary cilia, transporting small molecules and responding to farnesoid X receptor agonist. Integration of organoid-derived cholangiocytes with collagen-coated polyethersulfone hollow fiber membranes yielded bioengineered bile ducts that morphologically resembled native bile ducts and possessed polarized bile acid transport activity. As such, we present a novel in vitro model for studying and therapeutically modulating cholangiocyte function.
ISSN:1758-5090
1758-5090
DOI:10.1088/1758-5090/aac8fd