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 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 genetic modification comprises an insertion of a polynucleotide encoding a tolerogenic factor and/or survival factor. The universal donor cells may further comprise at least one genetic modification within or near a gene that encodes a survival factor, wherein said genetic modification comprises an insertion of a polynucleotide encoding a second tolerogenic factor and/or a different survival factor.

Disclosed are methods for treating or limiting development of diabetes, by transplanting into the eye of a subject with diabetes or at risk of diabetes an amount effective to treat or limit development of diabetes of insulin-producing cells engineered to reduce expression of a β3 subunit of Cav (Cavβ3).

Thin film devices, e.g., multilayer thin film devices, that encapsulate cells for transplantation into a subject are provided. Also provided are methods of using and methods of preparing the subject devices. The thin film devices include a first porous polymer layer and a second porous polymer layer that define a lumen therebetween and encapsulate a population of cells within the lumen. The thin film devices can promote vascularization into the lumen of the device via the pores in the first polymer layer and/or second polymer layer; limit foreign body response to the device; limit ingress of cells, immunoglobulins, and cytokines into the lumen via the first and the second polymer layers; and release from the first polymer layer and/or the second polymer layer molecules secreted by the population of cells.

The present invention provides methods to promote the differentiation of pluripotent stem cells. In particular, the present invention provides an improved method for the formation of pancreatic endoderm, pancreatic hormone expressing cells and pancreatic hormone secreting cells. The present invention also provides methods to promote the differentiation of pluripotent stem cells without the use of a feeder cell layer.

The present invention provides modified stem cells (SCs) and use of the SCs to treat disease.

Compositions of genetically modified beta-like cells are encompassed. Also encompassed are methods of treatment of type 1 diabetes using these compositions or compositions that inhibit the function of the identified genes.

A method of obtaining a pluripotent-like multipotent cell, including providing a cell of a first type which is not a pluripotent-like multipotent cell; contacting the cell of a first type with an agent capable of remodeling the chromatin and/or DNA of the cell; transiently increasing expression of at least one pluripotent gene regulator in the cell of a first type, to a level at which the at least one pluripotent gene regulator is capable of driving transformation of the cell of a first type into the pluripotent-like multipotent cell; and placing or maintaining the cell in a differentiation medium and maintaining intracellular levels of the at least one pluripotent gene regulator for a sufficient period of time to allow a stable pluripotent-like multipotent cell to be obtained; wherein the pluripotent-like multipotent cell so obtained does not exhibit teratoma formation in vivo.

An object of the present invention is to provide a novel approach capable of conveniently producing a large quantity of substantially uniform size cell aggregates. Provided is a method for producing cell aggregates using a cell culture bag, the cell culture bag having a lower face comprising a plurality of recesses, the method comprising the steps of: (1) adding cells and a medium to the cell culture bag, stirring the contents, and culturing the cells while applying a pressure to the cell culture bag; and (2) recovering the formed cell aggregates after the completion of culture.

The present invention relates to a method for isolating bona fide pancreatic progenitor cells and to cell populations enriched for bona fide pancreatic progenitor cells.

Among the various aspects of the present disclosure is the provision of methods and compositions for the generation of functionally mature beta cells having enhanced SIX2+ activity and therapeutic benefit and uses thereof. An aspect of the present disclosure provides for a method of generating SIX2-enhanced SC-β cells. In some embodiments, the method comprises providing a population of SC-β cells (or EP cells); providing a SIX2 positive regulator; and/or incubating the population of SC-β cells and the SIX2 positive regulator.