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Blood, Vol. 92 No. 9 (November 1), 1998:
pp. 3177-3188
Effect of FLT3 Ligand and Granulocyte Colony-Stimulating Factor on
Expansion and Mobilization of Facilitating Cells and Hematopoietic Stem
Cells in Mice: Kinetics and Repopulating Potential
Michael Neipp,
Tatiana Zorina,
Michele A. Domenick,
Beate G. Exner, and
Suzanne T. Ildstad
From the Institute for Cellular Therapeutics, Allegheny University of
the Health Sciences, Philadelphia, PA.
We have previously identified a cellular population in murine bone
marrow that facilitates engraftment of highly purified hematopoietic
stem cells (HSC) across major histocompatibility complex (MHC) barriers
without causing graft-versus-host disease. Here we investigated the
effect of flt3 ligand (FL) and granulocyte colony-stimulating factor
(G-CSF) on the mobilization of facilitating cells (FC) and HSC into
peripheral blood (PB). Mice were injected with FL alone (day 1 to 10),
G-CSF alone (day 4 to 10), or both in combination. The number of FC
(CD8+/  TCR /  TCR)
and HSC
(lineage/Sca-1+/c-kit+) was
assessed daily by flow cytometry. Lethally irradiated allogeneic mice
were reconstituted with PB mononuclear cells (PBMC). FL and G-CSF
showed a highly significant synergy on the mobilization of FC and HSC.
The peak efficiency for mobilization of FC (21-fold increase) and HSC
(200-fold increase) was reached on day 10. Our data further suggest
that the proliferation of FC and HSC induced by FL in addition to the
mobilizing effect mediated by G-CSF might be responsible for the
observed synergy of both growth factors. Finally, the engraftment
potential of PBMC mobilized with FL and G-CSF or FL alone was superior
to PBMC obtained from animals treated with G-CSF alone. Experiments
comparing the engraftment potential of day 7 and day 10 mobilized PBMC
indicate that day 10, during which both FC and HSC reached their
maximum, might be the ideal time point for the collection of both
populations. © 1998 by The American Society of Hematology.
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