Cambridge Enterprise Limited

Other

Vallier, Ludovic

Brons, I. Gabrielle M.

Pedersen, Roger

Ludovic Vallier

Roger Pedersen

Nicholas Hannan

Gabrielle Brons

Fotios Sampaziotis

Alessandro Bertero

Matthias Pawlowski

Mark Kotter

Daniel Ortmann

Nicholas W Morrell

Kourosh Saeb-Parsy

Hsin-hua Cho

Sheikh Tamir Rashid

Hsin-Hua Cho

Mark Ormiston

Amer Rana

Fotis Sampaziotis

I Gabrielle M Brons

The present invention relates to a stable method for introducing at least one inducible cassette into a cell, and permitting controllable transcription from within that inducible cassette. The method may be used for any cell type, from any eukaryotic organism, but has a particular application in the introduction of inducible cassettes into pluripotent stem cells, such as animal or human pluripotent stem cells (hPSCs). The inducible cassette is controllably inserted in such a way to ensure that the genetic material it contains is not silenced or subject to negative influences from the insertion site, and transcription of the genetic material is controlled.

Controllable transcription

This invention relates to the expansion of primary cholangiocytes in the form of cholangiocyte organoids (COs) using culture conditions in which canonical Wnt signalling is inhibited and non-canonical Wnt/PCP signalling is potentiated. Methods of expanding primary cholangiocytes, expanded populations of cholangiocytes and medical applications of expanded cholangiocytes are provided.

Methods of expanding cholangiocytes

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 TGF&#x3b2; 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 TGF&#x3b2; 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.

In vitro production of cholangiocytes

This invention relates to the differentiation of pluripotent cells (PSCs) into foregut stem cells (FSCs) using a definitive endoderm induction medium comprising a TGFfi ligand, fibroblast growth factor (FGF), bone morphogenetic protein (BMP) and a PI3K inhibitor to differentiate the pluripotent cells into definitive endoderm cells and a foregut induction medium comprising a TGF&#x3b2; ligand to differentiate the definitive endoderm cells into foregut stem cells (FSCs). Methods of differentiation, populations of foregut stem cells, culture media and kits are provided.

In vitro production of foregut stem cells

This invention relates to the use of late out-growth endothelial progenitor cells (L-EPCs) as a cellular substrate for the generation of Induced pluripotent stem cells (iPSCs). This may be useful in the production of patient-specific tissues for disease modelling, drug and toxicology screening, tissue replacement and delivery of gene therapy.

Cellular substrate for nuclear reprogramming

This invention relates to the in vitro differentiation of pluripotent cells into pancreatic progenitors by i) culturing pluripotent cells in a definitive endoderm (DE) medium comprising a TGFp ligand, fibroblast growth factor (FGF), bone morphogenetic protein (BMP), a PI3K inhibitor and optionally a GSK3 &#x3b2; inhibitor to produce a population of definitive endoderm cells, ii) culturing the definitive endoderm cells in a first pancreatic medium comprising an activin antagonist; FGF; retinoic acid; and a BMP inhibitor to produce a population of dorsal foregut cells; iii) culturing the dorsal foregut cells in a second pancreatic medium comprising FGF, retinoic acid, a BMP inhibitor, and a hedgehog signalling inhibitor, and; iv) culturing the endoderm cells in a third pancreatic medium comprising FGF. The progenitor cells thus produced may be further differentiated into pancreatic endocrine cells. These methods may be useful, for example, in producing pancreatic cells for therapy or disease modelling.

In vitro pancreatic differentiation of pluripotent mammalian cells

This invention relates to the induction of hepatic differentiation by culturing induced pluripotent stem (iPS) cells in an endoderm induction medium to produce a population of anterior definitive endoderm (ADE) cells and then culturing the population of ADE cells in a hepatic induction medium to produce a population of hepatic progenitor cells, which may be optionally differentiated into hepatocytes. The endoderm induction medium is a chemically defined medium which has fibroblast growth factor activity, stimulates SMAD2 and SMAD3 mediated signalling pathways and SMAD1, SMAD5 and SMAD9 mediated signalling pathways, and inhibits phosphatidylinositol 3-kinase (PI3K) and glycogen synthase kinase 3&#x3b2; (GSK3&#x3b2;); and the hepatic induction medium is a chemically defined medium which stimulates SMAD2 and SMAD3 mediated signalling pathways. These methods may be useful, for example, in producing hepatocytes and hepatic progenitor cells for cell-based therapies or disease modelling.

In vitro hepatic differentiation

The invention relates to the isolation and propagation of pluripotent cells isolated from the mammalian late epiblast layer, termed Epiblast Stem Cells (EpiSCs). These cells are useful in a range of applications, including the generation of transgenic animal species.

Pluripotent cells from mammalian late epiblast layer

Pluripotent cells from the mammalian late epiblast layer

This invention relates to the culture of pluripotent cells in a fully humanised chemically defined medium. Cells may be cultured over a prolonged period of time without losing their pluripotent status or may be controllably induced to differentiate into progenitor cells of the three primary germ layers by the addition of differentiation factors, for example differentiation factors which modulate one or more of the Activin/Nodal, FGF, Wnt or BMP signalling pathways.

Differentiation of pluripotent cells into primary germ layer progenitors

This invention relates to the isolation and propagation of pluripotent cells isolated from the mammalian late epiblast layer, termed Epiblast Stem Cells' (EpiSCs). These cells are useful in a range of applications, including the generation of transgenic animal species.

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Cambridge, United Kingdom

Ludovic Vallier