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 method for producing insulin in response to a hyperglycemic environment comprising contacting said environment with a population of human transgenic beta cells, wherein each transgenic human beta cell 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 method for producing insulin in response to a hyperglycemic environment comprising contacting said environment with a population of human transgenic beta cells, wherein each transgenic human beta cell comprises a vector comprising a nucleic acid sequence encoding human CXCL12, wherein said beta cell is resistant to human immune cells.
3 . The method of claim 2 , wherein the cell is an autologous beta cell obtained from a subject with type 1 diabetes.
4 . The method of claim 2 , wherein the cell is an allogenic beta cell.
5 . The method of claim 2 , wherein said human immune cells comprise NK cells, cytotoxic T cells and/or B cells.
6 . The method of claim 2 , wherein said cell expresses human CXCL12 at a fugetactic amount.
7 . The method of claim 6 , wherein said CXCL12 is CXCL12 alpha or CXCL12 beta.
8 . A method for producing insulin in response to a hyperglycemic environment comprising contacting said environment with a population of human transgenic beta cells, wherein each transgenic human beta cell comprises a transgenic regulatory region upstream of an endogenous CXCL12 coding region wherein said beta cell is resistant to human immune cells.
9 . The method of claim 8 , wherein the cell is an autologous beta cell.
10 . The method of claim 8 , wherein the cell is an allogenic beta cell.
11 . The method of claim 9 , wherein the cell is an autologous beta cell obtained or derived from a subject with type 1 diabetes.
12 . The method claim 10 , wherein the cell is an allogeneic beta cell obtained or derived from a subject free of type 1 diabetes.
13 . The method of claim 8 , wherein the transgenic regulatory region is an exogenous constitutive, or inducible promoter.
14 . The method of claim 8 , wherein the cell expresses CXCL12 at a fugetactic amount.
15 . The method of claim 14 , wherein said CXCL12 is CXCL12 alpha or CXCL12 beta.
16 . The method claim 15 , wherein the cell expresses CXCL12 beta.
17 . The method of claim 8 , wherein the beta cell is incapable of cell division.
18 . The method of claim 17 , wherein the human CXCL12 is selected from CXCL12 alpha, CXCL12 beta, CXCL12 delta, and CXCL12 gamma.
19 . The method of claim 8 , wherein said human immune cells comprise NK cells, cytotoxic T cells and B cells.
20 . A method for treating diabetes in a patient in need thereof, the method comprising contacting said environment with a population of human transgenic beta cells, wherein each transgenic human beta cell 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.