Peripheralization of hematopoietic stem cells

Abstract

The invention relates to in vivo peripheralization of CD34 + cells by administering anti-VLA-4 antibodies or anti-VCAM-1 antibodies.

1. A method of peripheralizing CD34 +  cells in vivo comprising the step of administering an anti-VLA-4 antibody or an anti-VCAM-1 antibody  which blocks the binding of VLA-4 antigen on the surface of the CD34 +  cells to VCAM  VCAM-   1   or fibronectin, and thereby increasing the number of CD 34   +    cells in the peripheral blood . 
     
     
       2. The method according to  claim 1 , wherein the anti-VLA-4 or anti-VCAM-1  antibody is a mouse/human,  chimeric antibody, single chain antibody, or humanized antibody, or Fab, Fab′, F(ab′) 2  or F(v) fragments thereof. 
     
     
       3. The method according to  claim 1 , wherein at least a portion of the CD34 +  cells are hematopoietic stem cells. 
     
     
       4. The method of  claim 1 , further comprising the step of administering a stimulating agent of CD34 +  cell proliferation in vivo, said stimulating agent being 5-fluorouracil or a cytokine that stimulates hematopoietic cells to proliferated  proliferate. 
     
     
       5. The method according to  claim 2 , further comprising the step of administering a stimulating agent of CD34 +  cell proliferation in vivo, said stimulating agent being 5-fluorouracil or a cytokine that stimulates hematopoietic cells to proliferated  proliferate. 
     
     
       6. The method according to  claim 3 , further comprising the step of administering a stimulating agent of hematopoietic stem cell proliferation in vivo, said stimulating agent being 5-fluorouracil or a cytokine that stimulates hematopoietic cells to proliferated  proliferate. 
     
     
       7. The method according to  claim 4 , wherein the stimulation is mediated by a cytokine selected from the group consisting of granulocyte colony-stimulating factor (G-CSF), stem cell factor, granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF), totipotent stem cell factor (T-SCF), stem cell proliferation factor (SCPF), interleukin-1 (IL-1), interleukin-2 (IL-2), interleukin-3 (IL-3), interleukin-4 (IL-4), interleukin-6 (IL-6) and interleukin-11 (IL-11). 
     
     
       8. The method according to  claim 5 , wherein the stimulation is mediated by a cytokine selected from the group consisting of granulocyte colony-stimulating factor (G-CSF), stem cell factor, granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF), totipotent stem cell factor (T-SCF), stem cell proliferation factor (SCPF), interleukin-1 (IL-1), interleukin-2 (IL-2), interleukin-3 (IL-3), interleukin-4 (IL-4), interleukin-6 (IL-6) and interleukin-11 (IL-11). 
     
     
       9. The method according to  claim 6 , wherein the stimulation is mediated by a cytokine selected from the group consisting of granulocyte colony-stimulating factor (G-CSF), stem cell factor, granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF), totipotent stem cell factor (T-SCF), stem cell proliferation factor (SCPF), interleukin-1 (IL-1), interleukin-2 (IL-2), interleukin-3 (IL-3), interleukin-4 (IL-4), interleukin-6 (IL-6) and interleukin-11 (IL-11). 
     
     
       10. The method according to  claim 7 , wherein the cytokine is G-CSF. 
     
     
       11. The method according to  claim 8 , wherein the cytokine is G-CSF. 
     
     
       12. The method according to  claim 9 , wherein the cytokine is G-CSF. 
     
     
       13. The method according to  claim 10 , wherein the G-CSF is administered before administering the anti-VLA-4 antibody or anti-VCAM-1 antibody . 
     
     
       14. The method according to  claim 11 , wherein the G-CSF is administered before administering the anti-VLA-4 antibody or anti-VCAM-1 antibody .