Method for homing hematopoietic stem cells to bone marrow stromal cells

Abstract

This invention pertains to a method for homing hematopoietic stem cells to bone marrow stromal cells in a host. The method comprises, administering to the host genetically-engineered hematopoietic stem cells capable of expressing a first member of a ligand-receptor binding pair. The stem cells are administered to the host under conditions whereby binding of the first member of the ligand-receptor binding pair to the second member of the ligand-receptor binding pair, present on stromal cells, occurs thereby homing the stem cells to the stromal cells. This method is useful for transplanting bone marrow in a host or in treating a host afflicted with a disease associated with a disorder of the bone marrow.

1 . A method for homing hematopoietic stem cells to bone marrow stromal cells in a host, comprising: 
 administering to the host genetically-engineered hematopoietic stem cells capable of expressing a first member of a ligand-receptor binding pair under conditions whereby binding of the first member of the ligand-receptor binding pair to a second member of the ligand-receptor binding pair, present on stromal cells, occurs thereby homing the stem cells to the stromal cells.    
     
     
         2 . A method for homing hematopoietic stem cells to bone marrow stromal cells in a host, comprising: 
 administering to the host stromal cells capable of expressing a first member of a ligand-receptor binding pair; and subsequently    administering to the host hematopoietic stem cells capable of expressing a second member of a ligand-receptor binding pair under conditions whereby binding of the ligand to the receptor occurs thereby homing the stem cells to the stromal cells, wherein either the stromal cells or the hematopoietic stem cells are genetically-engineered to provide the capability of expressing the appropriate ligand or receptor.    
     
     
         3 . A method according to  claim 2  wherein the ligand-receptor binding pair is selected from the group consisting transforming growth factor and transforming growth factor receptor or epidermal growth factor receptor; epidermal growth factor and epidermal growth factor receptor; tumor necrosis factor-α and tumor necrosis factor-receptor; interferon and interferon receptor; platelet derived growth factor and platelet derived growth factor receptor; transferrin and transferrin receptor; avidin and biotin or antibiotin; antibody and antigen pairs; interleukin and interleukin receptor; granulocyte-macrophage colony stimulating factor and granulocyte-macrophage colony receptor; macrophage colony stimulating factor and macrophage colony stimulating factor receptor; granulocyte colony stimulating factor and granulocyte colony stimulating factor receptor; and sugar molecules and sugar receptors.  
     
     
         4 . A method according to  claim 2  wherein the hematopoietic stem cells are 32D or a non-adherent stem cell derived from a human long term bone marrow culture.  
     
     
         5 . A method according to  claim 2  wherein the bone marrow stromal cells are selected from the group consisting of GBL/6, KM101, KM102, KM103, KM104 and K105.  
     
     
         6 . A method according to  claim 2  wherein the stromal cells are capable of expressing a ligand.  
     
     
         7 . A method according to  claim 6  wherein the ligand is pro-transforming growth factor-α.  
     
     
         8 . A method according to  claim 2  wherein the hematopoietic stem cells are capable of expressing a receptor.  
     
     
         9 . A method according to  claim 8  wherein the receptor is an epidermal growth factor receptor.  
     
     
         10 . A method according to  claim 2  wherein either the genetically-engineered stromal cells or hematopoietic stem cells are produced by transfecting the cells with a retroviral vector containing RNA which is reverse transcribed to DNA encoding a member of a ligand-receptor binding pair.  
     
     
         11 . A method for transplanting bone marrow in a host, comprising: 
 administering to the host stromal cells capable of expressing a first member of a ligand-receptor binding pair; and    administering to the host hematopoietic stem cells capable of expressing a second member of a ligand-receptor binding pair under conditions whereby binding of the ligand to the receptor occurs thereby homing the stem cells to the stromal cells, wherein either the stromal cells or hematopoietic stem cells are genetically-engineered to provide the capability of expressing the appropriate ligand or receptor.    
     
     
         12 . A method according to  claim 11  wherein the ligand is pro-transforming growth factor-α and the receptor is an epidermal growth factor receptor.  
     
     
         13 . A method according to  claim 11  wherein the hematopoietic stem cells are selected from the group consisting of 32D or a non-adherent stem cell derived from a human long term bone marrow culture.  
     
     
         14 . A method according to  claim 11  wherein the bone marrow stromal cells are selected from the group consisting of GBL/6, KM101, KM102, KM103, KM104 and KM105.  
     
     
         15 . A method according to  claim 11  wherein the stromal cells are capable of expressing a ligand.  
     
     
         16 . A method according to  claim 15  wherein the ligand is transforming growth factor-α.  
     
     
         17 . A method according to  claim 11  wherein the genetically-engineered hematopoietic stem cells are capable of expressing a receptor.  
     
     
         18 . A method according to  claim 17  wherein the receptor is an epidermal growth factor receptor.  
     
     
         19 . A method according to  claim 11  wherein the genetically-engineered stromal cells or the hematopoietic stem cells are produced by transfecting the cells with a retroviral vector containing RNA which is reverse transcribed to DNA encoding a member of a ligand-receptor binding pair.  
     
     
         20 . A method of treating a host afflicted with a disease associated with a disorder of the bone marrow, comprising: 
 administering to the host a therapeutically effective amount of stromal cells capable of expressing a first member of a ligand-receptor binding pair; and    administering to the host a therapeutically effective amount of hematopoietic stem cells capable of expressing a second member of a ligand-receptor binding pair under conditions whereby binding of the ligand to the receptor occurs, thereby homing the stem cells to the stromal cells, wherein either the stromal cells or hematopoietic stem cells are genetically-engineered to provide the capability of expressing the appropriate ligand or receptor.