Mobilization of early hematopoietic progenitor cells with BB-10010: a genetically engineered variant of human macrophage inflammatory protein- 1 alpha

BB-10010 is a genetically engineered variant of human macrophage inflammatory protein-1 alpha with improved solution properties. We show here that it mobilizes stem cells into the peripheral blood. We investigated the mobilizing effects of BB-10010 on the numbers of circulating 8-day spleen colony-forming units (CFU-S8), CFU-S12, and progenitors with marrow repopulating ability (MRA). A single subcutaneous dose of BB-10010 caused a twofold increase in circulating numbers of CFU-S8, CFU-S12, and MRA 30 minutes after dosing. We also investigated the effects of granulocyte colony-stimulating factor (G-CSF) and the combination of G-CSF with BB-10010 on progenitor mobilization. Two days of G-CSF treatment increased circulating CFU-S8, CFU-S12, and MRA progenitors by 25.7-, 19.8-, and 27.7-fold. A single administration of BB-10010 after 2 days of G-CSF treatment increased circulating CFU-S8, CFU-S12, and MRA even further to 38-, 33-, and 100-fold. Splenectomy resulted in increased circulating progenitor numbers but did not change the pattern of mobilization. Two days of treatment with G-CSF then increased circulating CFU-S8, CFU-S12, and MRA by 64-, 69-, and 32-fold. A single BB-10010 administration after G-CSF treatment further increased them to 85-, 117-, and 140-fold, respectively, compared with control. We conclude that BB-10010 causes a rapid increase in the number of circulating hematopoietic progenitors and further enhances the numbers induced by pretreatment with G-CSF. BB-10010 preferentially mobilized the more primitive progenitors with marrow repopulating activity, releasing four times the number achieved with G-CSF alone. Translated into a clinical setting, this improvement in progenitor cell mobilization may enhance the efficiency of harvest and the quality of grafts for peripheral blood stem cell transplantation.

Brief Note: Marrow Repopulating Ability of Peripheral Blood Cells Compared to Thoracic Duct Cells

Ten dogs were exposed to 1200 r. of whole body irradiation at a dose rate of 9.2 r./min. Five of these dogs were then given infusions of 21 to 74 x 109 autologous peripheral blood cells which had been previously stored at -80 C. 4.0 to 19.4 x 109 of these cells were lymphocytes, 0.4 to 4.9 x 109 were monocytes and 16.4 to 50.3 x 109 were granulocytes. All five dogs showed clinical or histologic evidence of bone marrow repopulation. The remaining 5 dogs were given 7 to 22 x 109 autologous thoracic duct lymphocytes. In none of these dogs was marrow repopulation observed. It was concluded that hemopoietic stem cells are not present in the thoracic duct lymph of the dog in any appreciable number.