title: Mobilization of primitive haemopoietic progenitor cells and stem cells with long-term repopulating ability into peripheral blood in mice by pegylated recombinant human megakaryocyte growth and development factor.
abstract: We investigated in detail the effect of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) on peripheral blood progenitor cell (PBPC) mobilization in male BDF1 mice. Treatment with PEG-rHuMGDF for 5 d stimulated a striking expansion of the circulating levels of multiple types of colony-forming units in culture (CFU-c), including CFU-granulocyte-macrophage, CFU-megakaryocyte, burst-forming units-erythroid, and multipotent CFU-c, and primitive day-12 CFU-spleen. All of these progenitors were mobilized into the peripheral blood (PB) with similar kinetics; their numbers peaked after the cessation of treatment and then declined earlier than platelet numbers peaked. The maximal increase in any of the four CFU-c in the PB was attained with at least 300 microg/kg/d of PEG-rHuMGDF, whereas peripheral platelet counts plateaued at 30 microg/kg/d. Adoptive transfer with PB from PEG-rHuMGDF-treated donor mice resulted in greater survival of lethally irradiated recipients. The majority of the recipients that survived at 187 d after transplantation with PEG-rHuMGDF-mobilized PB showed significant donor engraftment at the progenitor cell level. The combined administration of appropriate doses of PEG-rHuMGDF and recombinant human granulocyte colony-stimulating factor induced a synergistic increase in the circulating levels of the four CFU-c compared to either factor alone. These results indicate that PEG-rHuMGDF as a single agent can mobilize a full spectrum of PBPCs in mice.
authors.affiliation: Pharmaceutical Research Laboratory, Kirin Brewery Co. Ltd, Takasaki, Gunma, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Torii
authors.forename: Y
authors.initials: Y
authors.lastname: Nitta
authors.forename: H
authors.initials: H
authors.lastname: Akahori
authors.forename: T
authors.initials: T
authors.lastname: Tawara
authors.forename: T
authors.initials: T
authors.lastname: Kuwaki
authors.forename: K
authors.initials: K
authors.lastname: Ogami
authors.forename: T
authors.initials: T
authors.lastname: Kato
authors.forename: H
authors.initials: H
authors.lastname: Miyazaki
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D006410:Hematopoiesis / Q000187:drug effects / Q000528:radiation effects; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D008297:Male; D051379:Mice; D013926:Thrombopoietin / Q000494:pharmacology*
chemical_list: D013926:Thrombopoietin