Methods for reducing elevated glucose levels
Described herein are human transgenic beta cells expressing fugetactic levels of CXCL12 to a subject in need thereof. Also described herein are beta cells comprising a transgene comprising a nucleic acid sequence encoding CXCL12.
1. A method for producing insulin in a medium comprising a hyperglycemic glucose concentration which method comprises:
a) contacting said medium with a population of human beta cells genetically engineered with a nucleic acid encoding a human CXCL12 protein isoform, wherein said cells are characterized as having decreased cell death in the presence of human immune cells in vitro as compared to a population of human beta cells lacking such genetic engineering wherein said extent of cell death is assessed by release of lactate dehydrogenase (LDH) from cells that undergo cell death due to lysis provided that said resistance to cell death is evidenced by LDH levels of less than 50% in said genetically engineered human beta cells as compared to non-engineered human beta cells acting as a control when both of said cells are exposed to a 30:1 ratio of human immune cells to each of said genetically modified human beta cells and non-engineered human beta cells,
wherein said nucleic acid is operably linked to an exogenous promoter; and
wherein each of said population of genetically engineered human beta cells and said non-engineered human beta cells is obtained from a human stem cell that has been differentiated ex vivo into human beta cells, and
wherein said population of genetically engineered human beta cells is allogeneic; and
b) maintaining said contact under conditions wherein said genetically engineered, human beta cells express insulin in response to said glucose in said hyperglycemic medium.
2. The method of claim 1 , wherein the human CXCL12 protein isoform is selected from the group consisting of: SEQ ID NOs: 1 to 6.
3. The method of claim 1 , wherein said population of cells have been exposed to a senescence inducing agent.
4. The method of claim 2 , wherein the human CXCL12 protein isoform is SEQ ID NO. 2.
5. The method of claim 3 , wherein the human CXCL12 protein isoform is SEQ ID NO. 2.