Effect of FLT3 Ligand and Granulocyte Colony-Stimulating Factor on Expansion and Mobilization of Facilitating Cells and Hematopoietic Stem Cells in Mice: Kinetics and Repopulating Potential

• Published in: Blood 1998-11, Vol.92 (9), p.3177-3188
• Main Authors: Neipp, Michael, Zorina, Tatiana, Domenick, Michele A., Exner, Beate G., Ildstad, Suzanne T.
• Format: Article
• Language: English
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Biological and medical sciences; Bone Marrow Cells - drug effects; Bone Marrow Cells - physiology; Bone marrow, stem cells transplantation. Graft versus host reaction; Drug Synergism; Graft Survival; Granulocyte Colony-Stimulating Factor - pharmacology; Hematopoietic Stem Cell Mobilization - methods; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells - drug effects; Kinetics; Male; Medical sciences; Membrane Proteins - pharmacology; Mice; Mice, Inbred C57BL; Radiation Chimera; Recombinant Proteins - pharmacology; Transfusions. Complications. Transfusion reactions. Cell and gene therapy
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V92.9.3177

We have previously identified a cellular population in murine bone marrow that facilitates engraftment of highly purified hematopoietic stem cells (HSC) across major histocompatibility complex (MHC) barriers without causing graft-versus-host disease. Here we investigated the effect of flt3 ligand (FL) and granulocyte colony-stimulating factor (G-CSF) on the mobilization of facilitating cells (FC) and HSC into peripheral blood (PB). Mice were injected with FL alone (day 1 to 10), G-CSF alone (day 4 to 10), or both in combination. The number of FC (CD8+/αβTCR−/γδTCR−) and HSC (lineage−/Sca-1+/c-kit+) was assessed daily by flow cytometry. Lethally irradiated allogeneic mice were reconstituted with PB mononuclear cells (PBMC). FL and G-CSF showed a highly significant synergy on the mobilization of FC and HSC. The peak efficiency for mobilization of FC (21-fold increase) and HSC (200-fold increase) was reached on day 10. Our data further suggest that the proliferation of FC and HSC induced by FL in addition to the mobilizing effect mediated by G-CSF might be responsible for the observed synergy of both growth factors. Finally, the engraftment potential of PBMC mobilized with FL and G-CSF or FL alone was superior to PBMC obtained from animals treated with G-CSF alone. Experiments comparing the engraftment potential of day 7 and day 10 mobilized PBMC indicate that day 10, during which both FC and HSC reached their maximum, might be the ideal time point for the collection of both populations. © 1998 by The American Society of Hematology.