title: Growth factor treatment prior to low-dose total body irradiation increases donor cell engraftment after bone marrow transplantation in mice.
abstract: Low-toxicity conditioning regimens prior to bone marrow transplantation (BMT) are widely explored. We developed a new protocol using hematopoietic growth factors prior to low-dose total body irradiation (TBI) in recipients of autologous transplants to establish high levels of long-term donor cell engraftment. We hypothesized that treatment of recipient mice with growth factors would selectively deplete stem cells, resulting in successful long-term donor cell engraftment after transplantation. Recipient mice were treated for 1 or 7 days with growth factors (stem cell factor [SCF] plus interleukin 11 [IL-11], SCF plus Flt-3 ligand [FL], or granulocyte colony-stimulating factor [G-CSF]) prior to low-dose TBI (4 Gy). Donor cell chimerism was measured after transplantation of congenic bone marrow cells. High levels of donor cell engraftment were observed in recipients pretreated for 7 days with SCF plus IL-11 or SCF plus FL. Although 1-day pretreatments with these cytokines initially resulted in reduced donor cell engraftment, a continuous increase in time was observed, finally resulting in highly significantly increased levels of donor cell contribution. In contrast, G-CSF treatment showed no beneficial effects on long-term engraftment. In vitro stem cell assays demonstrated the effect of cytokine treatment on stem cell numbers. Donor cell engraftment and number of remaining recipient stem cells after TBI were strongly inversely correlated, except for groups treated for 1 day with SCF plus IL-11 or SCF plus FL. We conclude that long-term donor cell engraftment can be strongly augmented by treatment of recipient mice prior to low-dose TBI with hematopoietic growth factors that act on primitive cells.
authors.affiliation: Department of Stem Cell Biology, University of Groningen, The Netherlands.
authors.forename: Estelle J K
authors.initials: EJ
authors.lastname: Noach
authors.forename: Albertina
authors.initials: A
authors.lastname: Ausema
authors.forename: Jan H
authors.initials: JH
authors.lastname: Dillingh
authors.forename: Bert
authors.initials: B
authors.lastname: Dontje
authors.forename: Ellen
authors.initials: E
authors.lastname: Weersing
authors.forename: Imre
authors.initials: I
authors.lastname: Akkerman
authors.forename: Edo
authors.initials: E
authors.lastname: Vellenga
authors.forename: Gerald
authors.initials: G
authors.lastname: de Haan
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells; D016026:Bone Marrow Transplantation / Q000379:methods*; D002455:Cell Division / Q000187:drug effects; D005260:Female; D006085:Graft Survival / Q000187:drug effects*; D006133:Growth Substances / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D008099:Liver / Q000166:cytology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011829:Radiation Dosage; D013154:Spleen / Q000166:cytology; D014184:Transplantation, Homologous / Q000379:methods; D014916:Whole-Body Irradiation / Q000379:methods*
chemical_list: D006133:Growth Substances