title: Mobilization of hematopoietic stem cells with highest self-renewal by G-CSF precedes clonogenic cell mobilization peak.
abstract: Harvest of granulocyte colony-stimulating factor (G-CSF)-mobilized hematopoietic stem cells (HSCs) begins at day 5 of G-CSF administration, when most donors have achieved maximal mobilization. This is based on surrogate markers for HSC mobilization, such as CD34(+) cells and colony-forming activity in blood. However, CD34(+) cells or colony-forming units in culture (CFU-C) are heterogeneous cell populations with hugely divergent long-term repopulation potential on transplantation. HSC behavior is influenced by the vascular bed in the vicinity of which they reside. We hypothesized that G-CSF may mobilize sequentially cells proximal and more distal to bone marrow venous sinuses where HSCs enter the blood. We addressed this question with functional serial transplantation assays using blood and bone marrow after specific time points of G-CSF treatment in mice. We found that in mice, blood collected after only 48 hours of G-CSF administration was as enriched in serially reconstituting HSCs as blood collected at 5 days of G-CSF treatment. Similarly, mobilized Lin(-)CD34(+) cells were relatively enriched in more primitive Lin(-)CD34(+)CD38(-) cells at day 2 of G-CSF treatment compared with later points in half of human donors tested (n = 6). This suggests that in both humans and mice, hematopoietic progenitor and stem cells do not mobilize uniformly according to their maturation stage, with most potent HSCs mobilizing as early as day 2 of G-CSF.
authors.affiliation: Blood and Bone Diseases Program, Mater Research Institute, University of Queensland, Woolloongabba, QLD, Australia.
authors.forename: Ingrid G
authors.initials: IG
authors.lastname: Winkler
authors.affiliation: German Red Cross Blood Service, Institute Frankfurt, Frankfurt, Germany.
authors.forename: Eliza
authors.initials: E
authors.lastname: Wiercinska
authors.affiliation: Blood and Bone Diseases Program, Mater Research Institute, University of Queensland, Woolloongabba, QLD, Australia.
authors.forename: Valerie
authors.initials: V
authors.lastname: Barbier
authors.affiliation: Blood and Bone Diseases Program, Mater Research Institute, University of Queensland, Woolloongabba, QLD, Australia.
authors.forename: Bianca
authors.initials: B
authors.lastname: Nowlan
authors.affiliation: German Red Cross Blood Service, Institute Frankfurt, Frankfurt, Germany; Institute for Transfusion Medicine and Immunohematology, Goethe University, Frankfurt, Germany; Department of Medicine/Hematology, University of Washington, Seattle, WA.
authors.forename: Halvard
authors.initials: H
authors.lastname: Bonig
authors.affiliation: Blood and Bone Diseases Program, Mater Research Institute, University of Queensland, Woolloongabba, QLD, Australia; School of Medicine, University of Queensland, Herston, QLD, Australia. Electronic address: jp.levesque@mater.uq.edu.au.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Levesque
mesh_terms: D000818:Animals; D002453:Cell Cycle; D000066673:Cell Self Renewal; D005260:Female; D005434:Flow Cytometry; D006085:Graft Survival; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000494:pharmacology*; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D051379:Mice; D010641:Phenotype; D013997:Time Factors
chemical_list: D016179:Granulocyte Colony-Stimulating Factor