title: Hematopoietic stem and progenitor cells are differentially mobilized depending on the duration of Flt3-ligand administration.
abstract: 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.
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center PO Box 9600, 2300 RC Leiden, the Netherlands.
authors.forename: Evert-Jan F M
authors.initials: EJ
authors.lastname: de Kruijf
authors.forename: Henny
authors.initials: H
authors.lastname: Hagoort
authors.forename: Gerjo A
authors.initials: GA
authors.lastname: Velders
authors.forename: Willem E
authors.initials: WE
authors.lastname: Fibbe
authors.forename: Melissa
authors.initials: M
authors.lastname: van Pel
mesh_terms: 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
chemical_list: D008565:Membrane Proteins; C084881:flt3 ligand protein