Method for modulating stem cell growth

Abstract

In one embodiment, provided is a composition including a prostaglandin compound for modulating stem cell proliferation and/or differentiation in a mammalian subject. In another embodiment, the instant application is directed to a composition which includes a prostaglandin compound for modulating proliferation and/or differentiation of stem cells of a mammalian subject, in which the stem cells are contacted directly or indirectly with the composition of the invention.

What is claimed is: 
     
         1 . A method for modulating stem cell proliferation and/or differentiation in a mammalian subject, which comprises administering to the subject in need thereof an effective amount of a prostaglandin compound represented by the formula (I): 
       
         
           
           
               
               
           
         
         wherein L, M and N are hydrogen atom, hydroxy, halogen atom, lower alkyl, hydroxy(lower)alkyl, lower alkanoyloxy or oxo, wherein at least one of L and M is a group other than hydrogen, and the five-membered ring may have at least one double bond; 
         A is —CH 3 , or —CH 2 OH, —COCH 2 OH, —COOH or a functional derivative thereof; 
         B is single bond, —CH 2 —CH 2 —, —CH═CH—, —C≡C—, —CH 2 —CH 2 —CH 2 —, —CH═CH—CH 2 —, —CH 2 —CH═CH—, —C≡C—CH 2 — or —CH 2 —C≡C—; 
         Z is 
       
       
         
           
           
               
               
           
         
       
       or single bond
 wherein R 4  and R 5  are hydrogen, hydroxy, halogen, lower alkyl, lower alkoxy or hydroxy(lower)alkyl, wherein R 4  and R 5  are not hydroxy and lower alkoxy at the same time; 
 R 1  is a saturated or unsaturated bivalent lower or medium aliphatic hydrocarbon residue, which is unsubstituted or substituted with halogen, alkyl, hydroxy, oxo, aryl or heterocyclic group, and at least one of carbon atom in the aliphatic hydrocarbon is optionally substituted by oxygen, nitrogen or sulfur; and 
 Ra is a saturated or unsaturated lower or medium aliphatic hydrocarbon residue, which is unsubstituted or substituted with halogen, oxo, hydroxy, lower alkyl, lower alkoxy, lower alkanoyloxy, cyclo(lower)alkyl, cyclo(lower)alkyloxy, aryl, aryloxy, heterocyclic group or heterocyclic-oxy group; lower alkoxy; lower alkanoyloxy; cyclo(lower)alkyl; cyclo(lower)alkyloxy; aryl; aryloxy; heterocyclic group; heterocyclic-oxy. 
 
     
     
         2 . The method as described in  claim 1 , wherein the stem cells are stem cells of human origin stem cells. 
     
     
         3 . The method as described in  claim 1 , wherein the stem cells are progenitor cells. 
     
     
         4 . The method as described in  claim 1 , wherein the stem cells are embryonic stem cells, somatic stem cells or combinations thereof. 
     
     
         5 . The method as described in  claim 1 , wherein said prostaglandin compound is 16-mono or dihalogen-prostaglandin compound. 
     
     
         6 . The method as described in  claim 1 , wherein said prostaglandin compound is 15-keto-prostaglandin compound. 
     
     
         7 . The method as described in  claim 1 , wherein said prostaglandin compound is 13,14-dihydro-16-mono or dihalogen-prostaglandin compound. 
     
     
         8 . The method as described in  claim 1 , wherein said prostaglandin compound is 13,14-dihydro-15-keto-prostaglandin compound. 
     
     
         9 . The method as described in  claim 1 , wherein said prostaglandin compound is 13,14-dihydro-15-keto-16-mono or dihalogen-prostaglandin compound. 
     
     
         10 . The method as described in  claim 1 , wherein said prostaglandin compound is 13,14-dihydro-16-mono or difluoro-prostaglandin compound. 
     
     
         11 . The method as described in  claim 1 , wherein said prostaglandin compound is 15-keto-16-mono or difluoro-prostaglandin compound. 
     
     
         12 . The method as described in  claim 1 , wherein said prostaglandin compound is 13,14-dihydro-15-keto-16-mono or difluoro-prostaglandin compound. 
     
     
         13 . The method as described in  claim 1 , wherein said prostaglandin compound is 13,14-dihydro-16-mono or dihalogen-prostaglandin E compound. 
     
     
         14 . The method as described in  claim 1 , wherein said prostaglandin compound is 15-keto-16-mono or dihalogen-prostaglandin E compound. 
     
     
         15 . The method as described in  claim 1 , wherein said prostaglandin compound is 13,14-dihydro-15-keto-16-mono or dihalogen-prostaglandin E compound. 
     
     
         16 . The method as described in  claim 1 , wherein said prostaglandin compound is 13,14-dihydro-16,16-difluoro-prostaglandin E 1  compound. 
     
     
         17 . The method as described in  claim 1 , wherein said prostaglandin compound is 13,14-dihydro-15-keto-prostaglandin E 1  compound. 
     
     
         18 . The method as described in  claim 1 , wherein said prostaglandin compound is 11-deoxy-13,14-dihydro-15-keto-16,16-difluoro-prostaglandin E 1  compound. 
     
     
         19 . A method for modulating proliferation and/or differentiation of stem cells of a mammalian subject, which comprises contacting said stem cells with an effective amount of a prostaglandin compound represented by the formula (I): 
       
         
           
           
               
               
           
         
         wherein L, M and N are hydrogen atom, hydroxy, halogen atom, lower alkyl, hydroxy(lower)alkyl, lower alkanoyloxy or oxo, wherein at least one of L and M is a group other than hydrogen, and the five-membered ring may have at least one double bond; 
         A is —CH 3 , or —CH 2 OH, —COCH 2 OH, —COOH or a functional derivative thereof; 
         B is single bond, —CH 2 —CH 2 —, —CH═CH—, —C≡C—, —CH 2 —CH 2 —CH 2 —, —CH═CH—CH 2 —, —CH 2 —CH═CH—, —C≡C—CH 2 — or —CH 2 —C≡C—; 
         Z is 
       
       
         
           
           
               
               
           
         
       
       or single bond
 wherein R 4  and R 5  are hydrogen, hydroxy, halogen, lower alkyl, lower alkoxy or hydroxy(lower)alkyl, wherein R 4  and R 5  are not hydroxy and lower alkoxy at the same time; 
 R 1  is a saturated or unsaturated bivalent lower or medium aliphatic hydrocarbon residue, which is unsubstituted or substituted with halogen, alkyl, hydroxy, oxo, aryl or heterocyclic group, and at least one of carbon atom in the aliphatic hydrocarbon is optionally substituted by oxygen, nitrogen or sulfur; and 
 Ra is a saturated or unsaturated lower or medium aliphatic hydrocarbon residue, which is unsubstituted or substituted with halogen, oxo, hydroxy, lower alkyl, lower alkoxy, lower alkanoyloxy, cyclo(lower)alkyl, cyclo(lower)alkyloxy, aryl, aryloxy, heterocyclic group or heterocyclic-oxy group; lower alkoxy; lower alkanoyloxy; cyclo(lower)alkyl; cyclo(lower)alkyloxy; aryl; aryloxy; heterocyclic group; heterocyclic-oxy. 
 
     
     
         20 . The method according to  claim 19 , wherein said composition is contacted with the stem cells in vitro or ex vivo.