BONE-MARROW COLLECTED 14 DAYS AFTER IN-VIVO ADMINISTRATION OF GRANULOCYTE-COLONY-STIMULATING FACTOR AND STEM-CELL FACTOR TO MICE HAS 10-FOLD MORE REPOPULATING ABILITY THAN UNTREATED BONE-MARROW

We have examined the repopulating ability of bone marrow and periphera l blood cells collected immediately and at intervals after treatment o f donor mice with the combination of granulocyte colony-stimulating fa ctor (G-CSF) and stem cell factor (SCF). Using a competitive repopulat ion assay we showed that the repopulating ability of peripheral blood cells was highest immediately after cytokine treatment and declined to normal levels within 6 weeks of the termination of treatment with G-C SF and SCF. In contrast the repopulating ability of bone marrow cells was low immediately after cytokine treatment and increased to levels t hat were 10-fold or more greater than marrow from untreated mice by 14 days after termination of treatment with G-CSF and SCF. This high lev el of repopulating activity declined to normal levels by 6 weeks after termination of treatment with G-CSF and SCF. The high level of repopu lating ability was confirmed by injecting cells from G-CSF- and SCF-tr eated donors into unconditioned recipients. Peripheral blood cells col lected immediately after treatment with G-CSF and SCF engrafted into u nconditioned mice sevenfold better than an equivalent number of bone m arrow cells from untreated mice. Likewise, bone marrow cells collected 14 days after treatment of the donor animal with G-CSF and SCF engraf ted at 10-fold higher levels than an equivalent number of bone marrow cells from untreated mice. We conclude that the treatment of donor mic e with G-CSF and SCF causes a transient increase in the repopulating a bility of peripheral blood and later of bone marrow. These observation s may have applications to clinical hematopoietic stem cell transplant ation.