Bioengineered bile ducts recapitulate key cholangiocyte functions

Chen Chen; Paulus G M Jochems; Lucia Salz; Kerstin Schneeberger; Louis C Penning; Stan F J van de Graaf; Ulrich Beuers; Hans Clevers; Niels Geijsen; Rosalinde Masereeuw; Bart Spee

doi:10.1088/1758-5090/aac8fd

Bioengineered bile ducts recapitulate key cholangiocyte functions

Chen Chen, Paulus G M Jochems, Lucia Salz, Kerstin Schneeberger, Louis C Penning, Stan F J van de Graaf, Ulrich Beuers, Hans Clevers, Niels Geijsen, Rosalinde Masereeuw, Bart Spee

Hubrecht Institute

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

28 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	034103
Journal	Biofabrication
Volume	10
Issue number	3
DOIs	https://doi.org/10.1088/1758-5090/aac8fd
Publication status	Published - 12 Jun 2018

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title = "Bioengineered bile ducts recapitulate key cholangiocyte functions",

abstract = "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.",

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doi = "10.1088/1758-5090/aac8fd",

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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

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.

U2 - 10.1088/1758-5090/aac8fd

DO - 10.1088/1758-5090/aac8fd

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SN - 1758-5082

VL - 10

SP - 034103

JO - Biofabrication

JF - Biofabrication

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ER -

Bioengineered bile ducts recapitulate key cholangiocyte functions

Abstract

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