In vitro production of cholangiocytes
AssigneeCambridge Enterprise Limited
InventorsLudovic Vallier, Fotios Sampaziotis, Nicholas Hannan
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Abstract
This invention relates to the efficient generation of cholangiocyte progenitor (CP) cells. Foregut stem cells (FSCs) are cultured in a hepatic induction medium comprising bone morphogenetic protein (BMP) and a TGFβ signalling inhibitor to produce a population of hepatoblasts. The hepatoblasts are then cultured in a biliary induction medium comprising fibroblast growth factor (FGF), retinoic acid and a TGFβ ligand to produce a population of cholangiocyte progenitors (CPs). The cholangiocyte progenitors (CPs) may be matured into cholangiocyte-like cells (CLCs) that display functional properties of Common Bile Duct (CBD) cholangiocytes. Methods, kits, cell populations and uses of these cell populations are provided.
Claims17
A method for producing a population of cholangiocyte progenitors (CPs) comprising:
- (i) culturing a population of foregut stem cells (FSCs) in a hepatic induction medium comprising bone morphogenetic protein (BMP) and a TGFβ signalling inhibitor to produce a population of hepatoblasts, and
- (ii) culturing the population of hepatoblasts in a biliary induction medium comprising fibroblast growth factor (FGF), retinoic acid and a TGFβ ligand to produce a population of cholangiocyte progenitors (CPs), wherein the TGFβ signalling inhibitor is a compound selected from the group consisting of SB-431542, SB-505124, lefty, cerberus and follistatin;
- and the TGFβ ligand is a compound selected from the group consisting of Activin, TGFP, Nodal, and GDF3.
Dependencies are inferred from the claim text.