A method for increasing the mobilization of hematopoietic stem cells. The forced migration of hematopoietic stem/progenitor cells (HSPC) from the bone marrow (BM) into the peripheral blood (PB), termed mobilization, is important from a clinical point of view as a procedure that allows for the collection of HSPC for transplantation in leukemia patients. Granulocyte-colony stimulating factor (G-CSF), most frequently employed in the clinic, efficiently mobilizes HSPC after a few consecutive daily injections. Unfortunately, about 25 % of patients do not respond efficiently to currently recommended mobilization protocols and are termed poor mobilizers. The present invention provides a method of increasing mobilization of hematopoietic precursors from the bone marrow to the peripheral blood, by using either G-CSF with thrombin antagonists, or the antagonists alone.
• Improving the collection of stem cells from the peripheral blood of the donor
• Treatment of cancer (since solid tumors depend on bone marrow-derived cells for tumor vascularization and survival)
• Lower doses of G-CSF
• Shorten procedure
In the outlined technology it was found that enhancement of G-CSF levels is associated with enhancement of stem cell mobilization from the bone marrow to the spleen. Likewise, inhibitors of the interaction between thrombin and its receptors (known as PAR) could enhance the effect of G-CSF. Therefore, PAR antagonists are synergistic with G-CSF, leading to marked enhancement of stem cell mobilization.