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.

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.

A bioscaffold comprising a graphene matrix for use in cellular therapy is disclosed. In particular, a bioscaffold having a coating of dexamethasone on a three-dimensional graphene matrix is provided, wherein the bioscaffold elutes dexamethasone to reduce inflammatory responses following implantation of the bioscaffold in a subject. Having the dexamethasone released locally in the vicinity of the bioscaffold avoids the systemic side effects from conventional intravenous delivery while allowing the dexamethasone to modulate the inflammatory milieu within the transplantation microenvironment.

A bioscaffold comprising a graphene matrix for use in cellular therapy is disclosed. In particular, a bioscaffold having a coating of dexamethasone on a three-dimensional graphene matrix is provided, wherein the bioscaffold elutes dexamethasone to reduce inflammatory responses following implantation of the bioscaffold in a subject. Having the dexamethasone released locally in the vicinity of the bioscaffold avoids the systemic side effects from conventional intravenous delivery while allowing the dexamethasone to modulate the inflammatory milieu within the transplantation microenvironment.

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).

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).

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 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.

Disclosed herein are devices for use in transplanting cells. The devices can include a housing defining a cavity; and a support structure separating the cavity into a cell chamber and a reservoir chamber, wherein the support structure comprises a membrane for fluid communication between the cell chamber and reservoir chamber. The cell chamber can define a first opening comprising a microstructure containing an array of micro-channels, each having a diameter to facilitate growth of vascular tissues; and an array of micro-reservoirs, each having a diameter to facilitate housing of cell aggregates individually. The membrane can define a surface area that is at least 50% of a total surface area of the support structure. Methods of treating a subject for a disease condition, such as diabetes, are also disclosed.

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.