HEMATOPOIETIC PROGENITOR-CELL MOBILIZATION INTO THE PERIPHERAL-BLOOD OF MICE USING A COMBINATION OF RECOMBINANT RAT STEM-CELL FACTOR (RRSCF) AND RECOMBINANT HUMAN GRANULOCYTE-COLONY-STIMULATING FACTOR (RHG-CSF)

A significant increase in the hematopoietic stem cell (HSC) concentrat ion has been observed in the peripheral blood and spleen of mice treat ed with rhG-CSF alone or with a combination of rhG-CSF plus rrSCF. The longer the duration of cytokine treatment, the higher the stimulatory effect on stem cell mobilization. In addition, cytokine administratio n led to a reduced stem cell concentration in the bone marrow. The tot al amount of HSCs in the body did not change following cytokine admini stration. These data support the theory that stem cells are mobilized from the bone marrow into circulation, as opposed to expanding in bloo d and spleen. In sharp contrast to rhG-CSF alone, a combination of rhG -CSF plus rrSCF produced a strong increase in the self-maintenance abi lity of peripheral blood day 11 colony-forming units-spleen (CFU-S-11) . After 10 days of cytokine treatment, long-term culture initiating ce lls (LTC-IC) were seen in the peripheral blood; in normal mice, the co ntent of LTC-IC in the blood was below the detection level. The activa tion of stromal progenitors (cells capable of transferring the hematop oietic microenvironment) by cytokine treatment was observed here for t he first time. The results suggest that a combination of rhG-CSF plus rrSCF is more effective than rhG-CSF alone in obtaining a large amount of transplantable HSCs.