Use of Modified Pyrimidine Compounds to Promote Stem Cell Migration and Proliferation

Abstract

This invention provides cells and methods for stimulating proliferation and migration of endogenous and exogenous mammalian stem cells in vivo and in vitro. The invention provides reagents and methods for efficiently proliferating mammalian stem cells in an animal in need thereof and producing stem cells that can be re-introduced into an animal in need thereof to alleviate neurological and corporal disorders.

1 . A method of stimulating proliferation, migration or both proliferation and migration of endogenous mammalian neural stem cells or retinal stem cells or both neural and retinal stem cells in a mammal in need thereof to alleviate a neurological or corporal disorder, the method comprising administering an effective amount of a pyrimidine derivative of formula (1) or (2), or a pharmaceutically acceptable salt thereof, for an effective period to the mammal, 
       
         
           
           
               
               
           
         
       
       wherein R1 to R8 independently represent a hydrogen atom, a lower alkyl group, CH 3 OCH 2 CH 2 —, CH 2 CONH 2 , —COCH 3 , —COC 2 H 5  or —CH 2 OCOC 2 H 5 , and X represents NH, N—CH 3 , N—C 2 H 5 , N-ph, N—COOC 2 H 5 , N—SO 2 CH 3 , CH 2 , CHCH 3 , CHC 2 H 5 , —O— or —S— in which ph stands for a phenyl group. 
     
     
         2 . The method of  claim 1 , wherein the method stimulates proliferation of endogenous mammalian stem cells in vivo. 
     
     
         3 . The method of  claim 1 , wherein the method stimulates migration of endogenous mammalian stem cells in vivo. 
     
     
         4 . The method of  claim 1 , wherein the method stimulates proliferation and migration of endogenous mammalian stem cells in vivo. 
     
     
         5 . The method of  claim 1 , wherein the pyrimidine derivative is 2-piperadino-6-methyl-5-oxo-5,6-dihydro-(7H) pyrrole-[3,4-d]pyrimidine maleate (MS-818). 
     
     
         6 . The method of  claim 1 , wherein the pyrimidine derivative is 2-piperadino-6-methyl-5-oxo-5,6-dihydro-(7H) pyrrole-[2,3-d]pyrimidine maleate.