TY - JOUR
T1 - Bioengineered bile ducts recapitulate key cholangiocyte functions
AU - Chen, Chen
AU - Jochems, Paulus G.M.
AU - Salz, Lucia
AU - Schneeberger, Kerstin
AU - Penning, Louis C.
AU - Van De Graaf, Stan F.J.
AU - Beuers, Ulrich
AU - Clevers, Hans
AU - Geijsen, Niels
AU - Masereeuw, Rosalinde
AU - Spee, Bart
N1 - Publisher Copyright:
© 2018 IOP Publishing Ltd.
PY - 2018/6/12
Y1 - 2018/6/12
N2 - 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.
AB - 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.
KW - bile acid transport
KW - bioengineered bile duct
KW - cholangiocyte
KW - liver organoid
UR - http://www.scopus.com/inward/record.url?scp=85049938478&partnerID=8YFLogxK
U2 - 10.1088/1758-5090/aac8fd
DO - 10.1088/1758-5090/aac8fd
M3 - Article
C2 - 29848792
AN - SCOPUS:85049938478
SN - 1758-5082
VL - 10
JO - Biofabrication
JF - Biofabrication
IS - 3
M1 - 034103
ER -