Renal progenitor cells from embryonic stem cells

Abstract

The present invention relates to compositions and methods for inducing the differentiation of stem cells into renal progenitor cells. In particular, the present invention provides compositions containing activin-a, retinoic acid, and bmp-7, and variants thereof, for differentiating stem cells into renal cells containing tubular epithelia. In certain embodiments, the present invention provides stem cells cultured with compositions used to treat renal disease.

1 . A method for differentiating stem cells into renal epithelial cells comprising: 
 a) providing: 
 i) stem cells; and  
 ii) a composition comprising a first agent capable of activating the retinoic acid signaling pathway, a second agent capable of activating the activin-a pathway, and a third agent capable of activating the bmp-7 pathway; and  
   b) culturing said stem cells with said composition.    
     
     
         2 . The method of  claim 1 , wherein said culturing generates a population of renal epithelial cells.  
     
     
         3 . The method of  claim 1 , wherein said stem cells are embryonic stem cells.  
     
     
         4 . The method of  claim 3 , further comprising providing a host and transplanting at least a portion of said population of stem cells into said host.  
     
     
         5 . The method of  claim 4 , wherein said stem cells are provided from said host.  
     
     
         6 . The method of  claim 1 , wherein said culturing is under conditions whereby said cells retain their pluripotential phenotype after expansion.  
     
     
         7 . The method of  claim 1 , wherein said stem cells comprise human stem cells.  
     
     
         8 . A population of cells comprising renal epithelial cells generated by the method of  claim 1 .  
     
     
         9 . A composition comprising; 
 a) stem cells; and    b) retinoic acid, activin-a, and bmp-7 in sufficient concentration to induce differentiation of said stem cells into renal epithelial cells.    
     
     
         10 . The composition of  claim 9 , wherein said stem cells are embryonic stem cells.  
     
     
         11 . A method of generating renal proximal tubule cells, comprising: 
 a) providing 
 i) stem cells cultured with a composition comprising a first agent capable of activating the retinoic acid signaling pathway, a second agent capable of activating the activin-a pathway, and a third agent capable of activating the bmp-7 pathway; and  
 ii) cultured kidney rudiments;  
   b) contacting said stem cells cultured with said composition with said cultured kidney rudiments;    c) culturing said cultured kidney rudiments under conditions such that said rudiments develop proximal tubule cells.    
     
     
         12 . The method of  claim 11 , wherein said stem cells are embryonic stem cells.