TREATING DIABETES WITH GENETICALLY MODIFIED BETA CELLS
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 human beta cell that expresses or overexpresses a human fugetactic agent in an amount sufficient to render said beta cell resistant to human immune cells, wherein said beta cell is capable of expressing insulin and incapable of cell division.
2 . A human beta cell comprising a vector that itself comprises a nucleic acid sequence encoding human CXCL12 wherein said beta cell is resistant to human immune cells.
3 . The human beta cell of claim 2 , wherein the cell is an autologous beta cell obtained from a subject with type 1 diabetes.
4 . The human beta cell of claim 2 , wherein the cell is an allogenic beta cell.
5 . The human beta cell of claim 2 , wherein said human immune cells comprise NK cells, cytotoxic T cells and/or B cells.
6 . The human beta cell of claim 2 , wherein said cell expresses human CXCL12 at a fugetactic amount.
7 . The human beta cell of claim 6 , wherein said CXCL12 is CXCL12 alpha or CXCL12 beta.
8 . A human beta cell comprising a transgenic regulatory region upstream of an endogenous CXCL12 coding region wherein said beta cell is resistant to human immune cells.
9 . The human beta cell of claim 8 , wherein the cell is an autologous beta cell.
10 . The human beta cell of claim 8 , wherein the cell is an allogenic beta cell.
11 . The human beta cell of claim 9 , wherein the cell is an autologous beta cell obtained or derived from a subject with type 1 diabetes.
12 . The human beta cell of claim 10 , wherein the cell is an allogeneic beta cell obtained or derived from a subject free of type 1 diabetes.
13 . The human beta cell of claim 8 , wherein the transgenic regulatory region is an exogenous constitutive, or inducible promoter.
14 . The human beta cell of claim 8 , wherein the cell expresses CXCL12 at a fugetactic amount.
15 . The human beta cell of claim 14 , wherein said CXCL12 is CXCL12 alpha or CXCL12 beta.
16 . The human beta cell of claim 15 , wherein the cell expresses CXCL12 beta.
17 . The human beta cell of claim 2 , wherein the beta cell is incapable of cell division.
18 . The human beta cell of claim 17 , wherein the human CXCL12 is selected from CXCL12 alpha, CXCL12 beta, CXCL12 delta, and CXCL12 gamma.
19 . The human beta cell of claim 8 , wherein said human immune cells comprise NK cells, cytotoxic T cells and B cells.
20 . The human beta cell of claim 8 , wherein the beta cell is incapable of cell division.