CYCLOPHOSPHAMIDE GRANULOCYTE COLONY-STIMULATING FACTOR INDUCES HEMATOPOIETIC STEM-CELLS TO PROLIFERATE PRIOR TO MOBILIZATION/

We isolated hematopoietic stem cells (HSC) from mice treated with cycl ophosphamide (CY) and granulocyte colony-stimulating factor (G-CSF), A ll mobilized multipotent progenitor activity was contained in two popu lations: Thy-1(lo)Sca-1(+)Lin(-)Mac-1(-)CD4(-)c-kit(+) long-term recon stituting progenitors and Thy-1(lo)Sca-1(+)Lin(-)Mac-1(lo)CD4(-) trans iently reconstituting progenitors, CY/G-CSF treatment drove both long- term and transient multipotent progenitors into cycle, leading to a mo re than 12-fold expansion in the number of long-term self-renewing HSC prior to mobilization. After CY and 2 days of G-CSF treatment the num ber of bone marrow HSC began to decline and the number of blood and sp lenic HSC increased. HSC continued to proliferate in the bone marrow a nd spleen through 8 days of G-CSF treatment, but HSC released into the blood tended to be in G(0)/G(1) phase, Mobilized multipotent progenit ors isolated from the spleen were less efficient than normal bone marr ow multipotent progenitors in engrafting irradiated mice but did not d iffer in colony forming unit-spleen (CFU-S) activity or single cell in vitro assays of primitive progenitor activity, The data suggest that mobilized HSC isolated from the spleen are less efficient at homing to and engrafting the bone marrow of irradiated recipient mice.