Disclosed herein are compositions and methods related to differentiation of stem cells into pancreatic endocrine cells. In some aspects, the methods provided herein relate to generation of pancreatic β cell, α cell, δ cells, and EC cells in vitro. In some aspects, the disclosure provides pharmaceutical compositions including the cells generated according to the methods disclosed herein, as well as methods of treatment making use thereof.

The invention relates to improved methods for culturing an epithelial stem cell or an organoid comprising epithelial stem cells. The invention also relates to culture media suitable for use with said methods, organoids obtainable or obtained by said methods and uses of said culture methods, media and organoids in drug discovery and validation, toxicity assays, diagnostics and therapy.

The disclosure relates to stem cells and their therapeutic use in the treatment and/or prevention of pancreatic diseases or disorders. Provided herein are compositions comprising c-kit positive pancreatic stem cells and methods of preparing and using c-kit positive pancreatic stem cells for the treatment and/or prevention of pancreatic diseases or disorders.

The present invention provides devices and methods for delivering a population of cells or a therapeutic agent to a subject in need thereof.

The present invention relates to a method to differentiate pluripotent stem cells to a primitive streak cell population, in a stepwise manner for further maturation to definitive endoderm.

The present invention relates to a cryopreserved in vitro cell culture comprising human pancreatic progenitor cells that co-express pancreatic-duodenal homeobox factor-1 (PDX1) and NK6 homeobox 1 (NKX6.1) and are chromogranin negative. The present invention also relates to a method for cryopreserving an in vitro population of human pancreatic progenitor cells that co-express PDX1 and NKX6.1 and are chromogranin negative.

Provided herein are methods of producing β cells and precursors thereof utilizing a Wnt signaling inhibitor or PKC activator, or both. Also provided herein are in vitro cultures comprising said cells, methods of treating a subject with a disease characterized by high blood sugar levels over a prolonged period of time by administering said cells, and devices for encapsulating said cells.

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

Provided herein are methods of producing β cells and precursors thereof utilizing a Wnt signaling inhibitor or PKC activator, or both. Also provided herein are in vitro cultures comprising said cells, methods of treating a subject with a disease characterized by high blood sugar levels over a prolonged period of time by administering said cells, and devices for encapsulating said cells.

Genetically modified cells that are compatible with multiple subjects, e.g., universal donor cells, and methods of generating said genetic modified cells are provided herein. The universal donor cells comprise at least one genetic modification within or near at least one gene that encodes a survival factor, wherein the genetic modification comprises an insertion of a polynucleotide encoding a tolerogenic factor. The universal donor cells may further comprise at least one genetic modification within or near a gene that encodes one or more MHC-I or MHC-II human leukocyte antigens or a component or a transcriptional regulator of a MHC-I or MHC-II complex, wherein said genetic modification comprises an insertion of a polynucleotide encoding a second tolerogenic factor.