Compositions and methods of producing mammalian cell populations that include a high proportion of pancreatic beta cells are described herein. Such cell populations are useful for treatment of diabetes. Also provided are materials and methods for the direct differentiation of stem cells, such as embryonic stem cells, into functional pancreatic beta cells. The disclosure provides the benefit of direct differentiation, which results in the production of functional pancreatic beta cells efficiently and at low cost.

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 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 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.

The present invention provides methods, cell cultures and differentiation media to promote differentiation of pluripotent stem cells to pancreatic endocrine cells of a mature phenotype. The resulting pancreatic endocrine cells express single hormonal insulin, PDX1, NKX6.1, and MAFA. In one or more differentiation stages, culturing may be carried out in a culture vessel at the air-liquid interface.

The invention relates to purified, tissue-specific progenitors, methods of making and using such tissue-specific progenitors.

Fresh human pancreas tissue can be used as a source of cells when to identify and select a non-stem cell population that is predisposed to be a source for surrogate pancreatic cells that can be used in treating insulin-dependent diabetes. The progenitors of these surrogate pancreatic cells have no reprogramming genes integrated into their genomes, differentiate to the pancreatic lineage pursuant to a protocol that employs only defined reagents, and are substantially unable to differentiate to the mesodermal lineage.

Disclosed herein is a 3D-printed, biocompatible macroporous device that houses stem cell derived -cell (SC- cell) clusters within a degradable fibrin gel. Cluster sizes are used that avoid severe hypoxia within 3D-printed devices and a microwell-based technique is used for resizing clusters within this range. 3D-printed devices may function for at least 12 weeks, are retrievable, and maintain structural integrity.

Provided herein are systems and methods for identifying cell-specific differentiation markers. In particular, provided herein are systems and methods for generating induced pluripotent cells (IPS) from human cells, differentiating the IPS into differentiated cells, and identifying differentiation specific markers.

The invention relates to purified, tissue-specific progenitors, methods of making and using such tissue-specific progenitors.

Disclosed herein are methods, compositions, kits, and agents useful for inducing cell maturation, and isolated populations of SC- cells for use in various applications, such as cell therapy.

Disclosed herein are methods, compositions, kits, and agents useful for inducing cell maturation, and isolated populations of SC- cells for use in various applications, such as cell therapy.