Composition and method for improving function of embryonic kidney transplants

Abstract

Methods and compositions are disclosed for use with embryonic metanephric tissue so as to increase the functioning renal mass obtained upon transplantation into a recipient.

1 . Isolated embryonic metanephric tissue that has been treated with a growth factor composition comprising at least one growth factor for metanephric development, wherein said treated metanephric tissue has enhanced renal development or function in a recipient as compared to metanephric tissue which has not been treated with said growth factor composition.  
   
   
       2 . The isolated embryonic metanephric tissue according to  claim 1  wherein said growth factor is selected from the group consisting of insulin-like growth factor I, insulin-like growth factor II, vascular endothelial growth factor, transforming growth factor alpha, transforming growth factor beta, hepatocyte growth factor, fibroblast growth factors, platelet-derived growth factor, leukemia inhibitory factor, angiopoietins 1 and 2, bone morphogenetic proteins, nerve growth factor, vitamin A, and growth hormone.  
   
   
       3 . The isolated embryonic metanephric tissue of  claim 1  wherein said metanephric tissue is isolated from a donor selected from the group consisting of human, macaque, porcine, guinea pig, rabbit, rat, mouse, and hamster.  
   
   
       4 . The isolated embryonic metanephric tissue of  claim 1  wherein said embryonic metanephric tissue is porcine embryonic metanephric tissue.  
   
   
       5 . The isolated embryonic metanephric tissue according to  claim 4  wherein said metanephric tissue is taken from a pig between about embryonic day 20 and about embryonic day 30.  
   
   
       6 . The isolated embryonic metanephric tissue of  claim 1  wherein said metanephric tissue is isolated after the beginning of metanephric kidney formation and before the formation of metanephric blood vessels.  
   
   
       7 . The isolated embryonic metanephric tissue according to  claim 1  wherein said metanephric tissue contains metanephric blastema, segments or ureteric bud, and nephron precursors but does not contain glomeruli.  
   
   
       8 . The isolated embryonic metanephric tissue according to  claim 1  wherein said metanephric tissue comprises at least one whole metanephros with renal capsule intact.  
   
   
       9 . The isolated embryonic metanephric tissue according to  claim 1  wherein said metanephric tissue has fewer antigen-presenting cells or cell surface antigens as compared to embryonic metanephric tissue isolated after the formation of metanephric blood vessels.  
   
   
       10 . The isolated embryonic metanephric tissue according to  claim 1  wherein said metanephric tissue is less immunogenic to a host as compared to metanephric tissue isolated after the formation of metanephric blood vessels.  
   
   
       11 . Isolated porcine embryonic metanephric tissue.  
   
   
       12 . A composition comprising embryonic metanephric tissue and a growth factor composition.  
   
   
       13 . The composition of  claim 12  wherein said growth factor is selected from the group consisting of insulin-like growth factor I, insulin-like growth factor II, vascular endothelial growth factor, transforming growth factor alpha, transforming growth factor beta, hepatocyte growth factor, fibroblast growth factors, platelet-derived growth factor, leukemia inhibitory factor, angiopoietins 1 and 2, bone morphogenetic proteins, nerve growth factor, vitamin A, and growth hormone.  
   
   
       14 . The composition of  claim 12  wherein said embryonic metanephric tissue is selected from the group consisting of human, macaque, porcine, guinea pig, rabbit, rat, mouse, and hamster.  
   
   
       15 . The composition of  claim 12  wherein said embryonic metanephric tissue is porcine embryonic metanephric tissue.  
   
   
       16 . A method comprising contacting isolated embryonic metanephric tissue with a growth factor composition comprising at least one growth factor for metanephric growth.  
   
   
       17 . The method of  claim 16  wherein said growth factor is selected from the group consisting of insulin-like growth factor 1, insulin-like growth factor II, transforming growth factor alpha, transforming growth factor beta, hepatocyte growth factor, fibroblast growth factors, platelet-derived growth factor, leukemia inhibitory factor, angiopoietins 1 and 2, bone morphogenetic proteins, nerve growth factor, and growth hormone.  
   
   
       18 . The method of  claim 16  wherein said metanephric tissue is isolated from a donor selected from the group consisting of human, macaque, porcine, guinea pig, rabbit, rat, mouse, and hamster.  
   
   
       19 . The method of  claim 16  wherein said isolated embryonic metanephric tissue is porcine embryonic metanephric tissue.  
   
   
       20 . The method of  claim 16  further comprising transplanting the growth factor-treated metanephric tissue into a recipient.  
   
   
       21 . The method of  claim 20  wherein said growth factor-treated metanephric tissue is implanted next to said recipient's omentum.  
   
   
       22 . The method of  claim 20  wherein said growth factor-treated metanephric tissue is implanted under the renal capsule of said recipient's kidney.  
   
   
       23 . The method of  claim 20  wherein said implanting step allows said growth factor-treated metanephric tissue to vascularize and develop to form urine.  
   
   
       24 . The method of  claim 20  wherein upon transplantation into said recipient said growth-factor treated embryonic metanephric tissue forms a renal mass with greater renal function as compared to the renal function of the renal mass formed by embryonic metanephric tissue which has not been treated with said growth factor composition.  
   
   
       25 . The method of  claim 20  wherein the recipient is human.  
   
   
       26 . The method of  claim 20  wherein the recipient is juvenile or adult.  
   
   
       27 . A chimeric kidney comprising tissue derived from embryonic metanephric tissue.  
   
   
       28 . The chimeric kidney of  claim 27  wherein said embryonic metanephric tissue is selected from the group consisting of human, macaque, porcine, guinea pig, rabbit, rat, mouse, and hamster.  
   
   
       29 . The chimeric kidney of  claim 27  wherein said embryonic metanephric tissue is porcine embryonic metanephric tissue.