Plasmin therapy to enhance heamatopoetic stem cell mobilization; Plasmin inhibitors to inhibit Leukemogenesis

Plasmin agonists can be used to enhance HSC mobilization to treat leukopenia and neutropenia more effectively, whether resulting from chemotherapy or not.
Plasmin antagonists can be used to inhibit HSC mobilization to assist in treating malignant disorders such as leukemia, lymphoma and myeloma.

Summary of the Invention

Transplantation of hematopoietic stem cells (HSC) is common practice in the treatment of various hematological diseases, such as leucopenia or leukemia. The therapeutic success of mobilization of sufficient numbers of HSC’s to the peripheral blood with G-CSF prior to donation is limited due to refractoriness to G-CSF.
Well-known and broadly available plasmin agonists, such as microplasmin, tPA and uPA, enhance the recruitment of HSCs:

  • In vivo administration of microplasmin or tenecteplase in combination with G-CSF was up to 3x as efficient as administration of G-CSF alone
  • Peripheral blood collected from AMI patients before and after thrombolytic treatment with tPA, showed that the number of HSCs was 4-fold increased after that treatment

Conversely, plasmin antagonists can be used to inhibit recruitment of HSCs in leukemia, as was indirectly evidenced in vivo in mice deficient in plasminogen/plasmin.

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