Hematopoietic stem and progenitor cells are differentially mobilized depending on the duration of Flt3-ligand administration.
BACKGROUND
Flt3-ligand is a cytokine that induces relatively slow mobilization of hematopoietic cells in animals and humans in vivo. This provides a time-frame to study hematopoietic stem and progenitor cell migration kinetics in detail.


METHODS
Mice were injected with Flt3-ligand (10 microg/day, intraperitoneally) for 3, 5, 7 and 10 days. Mobilization of hematopoietic stem and progenitor cells was studied using colony-forming-unit granulocyte/monocyte and cobblestone-area-forming-cell assays. The radioprotective capacity of mobilized peripheral blood mononuclear cells was studied by transplantation of 1.5 x 10(6) Flt3-ligand-mobilized peripheral blood mononuclear cells into lethally irradiated (9.5 Gy) recipients.


RESULTS
Hematopoietic progenitor cell mobilization was detected from day 3 onwards and prolonged administration of Flt3-ligand produced a steady increase in mobilized progenitor cells. Compared to Flt3-ligand administration for 5 days, the administration of Flt3-ligand for 10 days led to a 5.5-fold increase in cobblestone-area-forming cells at week 4 and a 5.0-fold increase at week 5. Furthermore, transplantation of peripheral blood mononuclear cells mobilized by 5 days of Flt3-ligand administration did not radioprotect lethally irradiated recipients, whereas peripheral blood mononuclear cells mobilized by 10 days of Flt3-Ligand administration did provide 100% radioprotection of the recipients with significant multilineage donor chimerism. Compared to the administration of Flt3-ligand or interleukin-8 alone, co-administration of interleukin-8 and Flt3-ligand led to synergistic enhancement of hematopoietic stem and progenitor cell mobilization on days 3 and 5.


CONCLUSIONS
These results indicate that hematopoietic stem and progenitor cells show different mobilization kinetics in response to Flt3-ligand, resulting in preferential mobilization of hematopoietic progenitor cells at day 5, followed by hematopoietic stem cell mobilization at day 10.
de Kruijf
Evert-Jan F M
EJ
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center PO Box 9600, 2300 RC Leiden, the Netherlands.
Hagoort
Henny
H
Velders
Gerjo A
GA
Fibbe
Willem E
WE
van Pel
Melissa
M
D000818:Animals; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000502:physiology; D008565:Membrane Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D013997:Time Factors
D008565:Membrane Proteins; C084881:flt3 ligand protein