Methods to mobilize progenitor/stem cells

Abstract

Methods to elevate progenitor and stem cell counts in animal subjects using compounds which bind to the chemokine receptor CXCR4 are disclosed. Preferred embodiments of such compounds are of the formula Z-linker-Z′  (1) or pharmaceutically acceptable salt thereof wherein Z is a cyclic polyamine containing 9-32 ring members of which 3-8 are nitrogen atoms, said nitrogen atoms separated from each other by at least 2 carbon atoms, and wherein said heterocycle may optionally contain additional heteroatoms besides nitrogen and/or may be fused to an additional ring system; or Z is of the formula wherein A comprises a monocyclic or bicyclic fused ring system containing at least one N and B is H or an organic moiety of 1-20 atoms, Z′ may be embodied in a form as defined by Z above, or alternatively may be of the formula —N(R)—(CR 2 ) n —X wherein each R is independently H or straight, branched or cyclic alkyl (1-6C), n is 1 or 2, and X is an aromatic ring, including heteroaromatic rings, or is a mercaptan; “linker” represents a bond, alkylene (1-6C) or may comprise aryl, fused aryl, oxygen atoms contained in an alkylene chain, or may contain keto groups or nitrogen or sulfur atoms.

1 . A method of enhancing the success of hematopoietic stem cell transplantation following immunosuppressive treatments, the method comprising:
 (a) administering 1,1′-[1,4-phenylene-bis-(methylene)]-bis-1,4,8,11-tetraazacyclotetradecane to a subject in an amount effective to mobilize progenitor and/or stem cells into the peripheral blood of said subject; followed by   (b) harvesting said progenitor and/or stem cells for use in hematopoietic stem cell transplantation following immunosuppressive treatments.   
     
     
         2 . The method of  claim 1 , further comprising (c) transplanting said progenitor and/or stem cells to the subject following immunosuppressive treatments. 
     
     
         3 . A method of enhancing the success of hematopoietic stem cell transplantation following immunosuppressive treatments, the method comprising:
 (a) administering 1,1′-[1,4-phenylene-bis-(methylene)]-bis-1,4,8,11-tetraazacyclotetradecane to a first subject in an amount effective to mobilize progenitor and/or stem cells into the peripheral blood of said first subject; followed by   (b) harvesting said progenitor and/or stem cells; and   (c) transplanting said progenitor and/or stem cells to a second subject following administration of immunosuppressive treatments to that second subject.   
     
     
         4 . A method of enhancing wound healing, comprising administering to a subject 1,1′-[1,4-phenylene-bis-(methylene)]-bis-1,4,8,11-tetraazacyclotetradecane in an amount effective to mobilize progenitor and/or stem cells into the peripheral blood of said subject. 
     
     
         5 . A method of treating burns, comprising administering to a subject 1,1′-[1,4-phenylene-bis-(methylene)]-bis-1,4,8,11-tetraazacyclotetradecane in an amount effective to mobilize progenitor and/or stem cells into the peripheral blood of said subject. 
     
     
         6 . A method of treating bacterial inflammation, comprising administering to said subject 1,1′-[1,4-phenylene-bis-(methylene)]-bis-1,4,8,11-tetraazacyclotetradecane in an amount effective to mobilize progenitor and/or stem cells into the peripheral blood of said subject.