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.

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.

The present invention relates to methods for encapsulating pancreatic progenitors in a biocompatible semi-permeable encapsulating device. The present invention also relates to production of human insulin in a mammal in response to glucose stimulation.

Provided in the present invention are uses of a compound as represented by formula I in preparing a stem cell apoptosis antagonist. Also provided are uses of the compound as represented by formula I in preparing a medicament for preventing or treating cell apoptosis-related diseases, and a culturing method employing the compound as represented by formula I for stem cell culturing. The compound as represented by formula I is (I). ##STR00001##

Disclosed herein are cell cultures and enriched cell populations of endocrine precursor cells, immature pancreatic hormone-expressing cells and mature pancreatic hormone-expressing cells. Also disclosed herein are methods of producing such cell cultures and cell populations.

A bioartificial device, such as a bioartificial pancreas, for implantation in a patient's vascular system. The bioartificial pancreas includes a scaffold adapted to engage an interior wall of a blood vessel, a cellular complex support by the scaffold and extending longitudinally within the interior cavity of the scaffold so as to be exposed to the blood flow when the scaffold is engaged with the blood vessel, the cellular complex support comprising one or more pockets bordered by thin film; and cellular complex comprising pancreatic islets disposed in the one or more pockets, the thin film being adapted to permit oxygen and glucose to diffuse from flowing blood into the one or more pockets at a rate sufficient to support the viability of the islets. The invention also includes methods of making and using a bioartificial pancreas.

A population of enteroendocrine cells (EEC) is obtained from a mammalian post-natal cell population, such as a population including post-natal stem cells, by treating the population with a plurality of small molecules that upregulate ChgA and promote differentiation of the cells to form the enteroendocrine cells. The upregulation of ChgA is such that the fraction of cells expressing CGA in the obtained cell population, as measured by a ChgA Immunostaining Assay, is at least about 1.5%. Small molecules that can be used to differentiate the post-natal cells into the enteroendocrine cells can include at least one of a Wnt activator, a Notch inhibitor, a Wnt inhibitor, a MEK/ERK inhibitor, a growth factor, a HDAC inhibitor, a Histone Methylation Inhibitor, a Tgf-β inhibitor, and a NeuroD1 activator. Also, the insulin expression of a population of mammalian cells is increased by treating the population with a plurality of small molecules that increase the insulin expression.

An object of the present invention is to provide an endodermal cell population for obtaining optimal somatic cells as cell therapy preparations. The endodermal cell population of the present invention has a reduced content proportion of undifferentiated cells in the cell population and contains endodermal cells differentiable into optimal somatic cells as cell therapy preparations. Further, a somatic cell derived from the endodermal cell population of the present invention has excellent therapeutic effects as a cell therapy preparation.

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.

The purpose of the present invention is to provide a novel method for making it possible to efficiently induce/produce endocrine cells from pluripotent stem cells. Insulin-producing cells including cells that are insulin-positive and NKX6.1-positive cells in a ratio of at least 30% and cells that are insulin-positive and NKX6.1-negative in a ratio of more than 15%.