Means and methods for the recruitment and identification of stem cells

Abstract

Described are methods of modulating stem/progenitor cell recruitment involving molecules that agonize the formation of plasmin stimulating the recruitment of stem/progenitor cells, including hematopoietic and endothelial precursor cells. Conversely, antagonists of plasmin can inhibit recruitment of the stem cells. In addition, the identification of the uPA receptor (uPAR) as a retention signal for stem cells in their niche suggests a novel method for increased engraftment and isolation of multipotent stem cells.

1 . A method for inhibiting recruitment of stem cells selected from the group consisting of bone marrow stem cells, bone marrow progenitor cells, and combinations thereof, the method comprising:
 introducing a plasmin-modulator to the stem cells so as to inhibit the recruitment of bone marrow stem cells and/or bone marrow progenitor cells.   
     
     
         2 . The method according to  claim 1  wherein said stem cell is hematopoietic. 
     
     
         3 . The method according to  claim 1  wherein said stem cell is an endothelial progenitor cell. 
     
     
         4 . The method according to  claim 1  wherein said plasmin modulator is selected from the group consisting of PAI-1, PAI-2, alpha-2 anti-plasmin, an antibody against t-PA, an antibody against u-PA, an antibody against plasminogen, an antibody against plasmin, an antibody against annexin II, an antibody against alpha-enolase. 
     
     
         5 . The method according to  claim 4 , wherein said stem cell is hematopoietic. 
     
     
         6 . The method according to  claim 4 , wherein said progenitor cell is an endothelial progenitor cell. 
     
     
         7 . The method according to  claim 4 , wherein inhibition of stem cells and/or progenitor cells recruitment is utilized in the treatment of a disorder selected from the group consisting of myeloproliferative disorders, leukemias, myelodysplastic disorders, myelofibrosis, polycetemia vera, Hodgkin lymphoma, non-Hodgkin lymphoma, essential thrombocytosis, multiple myeloma, and combinations of any thereof. 
     
     
         8 . The method according to  claim 5 , wherein inhibition of stem cells and/or progenitor cells recruitment is utilized in the treatment of a disorder selected from the group consisting of myeloproliferative disorders, leukemias, myelodysplastic disorders, myelofibrosis, polycetemia vera, Hodgkin lymphoma, non-Hodgkin lymphoma, essential thrombocytosis, multiple myeloma, and combinations of any thereof. 
     
     
         9 . The method according to  claim 6 , wherein inhibition of stem cells and/or progenitor cells recruitment is utilized in the treatment of a disorder selected from the group consisting of myeloproliferative disorders, leukemias, myelodysplastic disorders, myelofibrosis, polycetemia vera, Hodgkin lymphoma, non-Hodgkin lymphoma, essential thrombocytosis, multiple myeloma, and combinations of any thereof.