Immunologically privileged cells and uses thereof

Abstract

The invention is directed to immunologically privileged cells, e.g., autologous, allogeneic, and xenogeneic intermediate lobe pituitary cells, for delivering polypeptides, e.g., insulin, to a subject, and to methods of using the same.

1 . A purified preparation of intermediate lobe pituitary cells that comprise a nucleic acid sequence encoding insulin operatively linked to a heterologous promoter that directs expression of the insulin nucleic acid sequence in the intermediate lobe pituitary cells.  
     
     
         2 . The cells of  claim 1 , wherein the cells are capable of storing insulin.  
     
     
         3 . The cells of  claim 1 , wherein the cells are capable of secreting insulin.  
     
     
         4 . The cells of  claim 1 , wherein the cells are capable of storing and secreting insulin.  
     
     
         5 . The cells of  claim 1 , wherein the heterologous promoter is other than the insulin promoter.  
     
     
         6 . The cells of  claim 1 , wherein the heterologous promoter is active in or specific for the intermediate lobe pituitary cells.  
     
     
         7 . The cells of  claim 1 , wherein the promoter is a pro-opiomelanocortin (POMC) promoter.  
     
     
         8 . The cells of  claim 1 , wherein the insulin is from a first species and the intermediate lobe pituitary cells are from a second species.  
     
     
         9 . The cells of  claim 1 , wherein the nucleic acid sequence encodes human insulin.  
     
     
         10 . The cells of  claim 1 , wherein the intermediate lobe pituitary cells are human cells.  
     
     
         11 . The cells of  claim 1 , wherein the intermediate lobe pituitary cells are fetal or post-natal cells.  
     
     
         12 . The cells of  claim 1 , wherein the cells further express a protein that promotes the transport of glucose across the plasma membrane.  
     
     
         13 . The cells of  claim 1 , wherein the cells express a glucokinase with a high K m  for glucose.  
     
     
         14 . The cells of  claim 13 , wherein the glucokinase is the β-cell isoform of glucokinase.  
     
     
         15 . The cells of  claim 1 , wherein the cells further express an ion channel.  
     
     
         16 . The cells of  claim 15 , wherein the ion channel is a K + /ATP channel.  
     
     
         17 . The cells of  claim 1 , wherein the cells further express glucagon-like peptide-1 (GLP-1).  
     
     
         18 . The cells of  claim 1 , wherein the cells further express glucose transporter-2 (GLUT-2).  
     
     
         19 . The cells of  claim 1 , wherein the cells are encapsulated within a non-antigenic compound.  
     
     
         20 . The cells of  claim 19 , wherein the compound is a polymer.  
     
     
         21 . The cells of  claim 19 , wherein the compound is a hydrogel, alginate or semipermeable fiber.  
     
     
         22 . A purified population of intermediate lobe pituitary cells, wherein the cells comprise an insulin-encoding nucleic acid sequence operatively linked to a control region that allows expression in the cells, and one or more of: 
 a nucleic acid sequence that encodes glucose transporter-2 (GLUT-2) operatively linked to a control region that allows expression of the GLUT-2 in the cells;    a nucleic acid sequence that encodes the β-cell isoform of glucokinase operatively linked to a control region that allows expression of the glucokinase in the cells;    a nucleic acid sequence that encodes an ion channel operatively linked to a control region that allows expression of the ion channel in the cells; and    a nucleic acid that encodes glucagon-like peptide-1 (GLP-1) operatively linked to a control region that allows expression of the GLP-1 in the cells.    
     
     
         23 . The purified population of intermediate lobe pituitary cells of  claim 19 , wherein the cells comprise an insulin-encoding nucleic acid sequence operatively linked to a control region that allows expression of the insulin in the cells, and: 
 a nucleic acid sequence that encodes glucose transporter-2 (GLUT-2) operatively linked to a control region that allows expression of the GLUT-2 in the cells;    a nucleic acid sequence that encodes the β-cell isoform of glucokinase operatively linked to a control region that allows expression of the glucokinase in the cells;    a nucleic acid sequence that encodes an ion channel operatively linked to a control region that allows expression of the ion channel in the cells; and    a nucleic acid that encodes glucagon-like peptide-1 (GLP-1) operatively linked to a control region that allows expression of the GLP-1 in the cells.    
     
     
         24 . The cells of  claim 22 , wherein the ion channel is a K+/ATP ion channel.  
     
     
         25 . The cells of  claim 23 , wherein the ion channel is a K+/ATP ion channel.