Quantitative and cell-cycle differences in progenitor cells mobilized by
recombinant human interleukin-7 and recombinant human granulocyte
colony-stimulating factor
KJ Grzegorzewski, KL Komschlies, JL Franco, FW Ruscetti, JR Keller and RH Wiltrout
Intramural Research Support Program, SAIC Frederick, MD, USA.
Administration of recombinant human interleukin-7 (rhIL-7) to mice
increases the exportation of myeloid progenitors (colony-forming unit
[CFU]-c and CFU-granulocyte erythroid megakaryocyte macrophage [CFU- GEMM])
from the bone marrow (BM) to peripheral organs, including blood, and also
increases the number of primitive progenitor and stem cells in the
peripheral blood (PB). We now report that combined treatment of mice with
rhIL-7 and recombinant human granulocyte-colony stimulating factor
(rhG-CSF) stimulates a twofold to 10-fold increase in the total number of
PB CFU-c, and a twofold to fivefold increase in the total number of PB
CFU-spleen at day 8 (CFU-S8) over the increase stimulated by rhIL-7 or
rhG-CSF alone. In addition, the quality of mobilized cells with trilineage,
long-term marrow-repopulating activity is maintained or increased in mice
treated with rhIL-7 and rhG-CSF compared with rhIL- 7 or rhG-CSF alone.
These differences in mobilizing efficiency suggest qualitative differences
in the mechanisms by which rhIL-7 and rhG-CSF mobilize progenitor cells, in
fact, the functional status of progenitor cells mobilized by rhIL-7 differs
from that of cells mobilized by rhG- CSF in that the incidence of actively
cycling (S-phase) progenitors obtained from the PB is about 20-fold higher
for rhIL-7-treated mice than for mice treated with rhG-CSF. These results
suggest the use of rhIL-7-mobilized progenitor/stem cells for
gene-modification and tracking studies, and highlight different functions
and rates of repopulation after reconstitution with PB leukocytes obtained
from mice treated with rhIL-7 versus rhG-CSF.
Volume 88,
Issue 11,
pp. 4139-4148,
12/01/1996
Copyright © 1996 by The American Society of Hematology
