G-CSF increases mesenchymal precursor cell numbers in the bone marrow via an indirect mechanism involving osteoclast-mediated bone resorption.
During the course of studies to investigate whether MPC circulate in response to G-CSF, the agent most frequently used to induce mobilization of hematopoietic progenitors, we observed that while G-CSF failed to increase the number of MPC in circulation (assayed in vitro as fibroblast colony-forming cells, CFU-F), G-CSF administration nevertheless resulted in a time-dependent increase in the absolute number of CFU-F within the BM, peaking at Day 7. Treatment of BM cells from G-CSF-treated mice with hydroxyurea did not alter CFU-F numbers, suggesting that the increase in their numbers in response to G-CSF administration is not due to proliferation of existing CFU-F. Given previous studies demonstrating that G-CSF potently induces bone turnover in mice, we hypothesized that the increase in CFU-F may be triggered by the bone resorption that occurs following G-CSF administration. In accord with this hypothesis, administration of an inhibitor of osteoclast differentiation, osteoprotegerin (OPG), prevented the increase of CFU-F numbers induced by G-CSF. In conclusion, these data indicate that the cytokine treatment routinely used to mobilize hematopoietic stem cells could provide a readily applicable method to induce in vivo expansion of MPC for clinical applications.
Brouard
Nathalie
N
Center for Stem Cell Research, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, 1825 Pressler Street, Houston, TX 77030, USA. Nathalie.Brouard@uth.tmc.edu
Driessen
Rebecca
R
Short
Brenton
B
Simmons
Paul J
PJ
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects*; D001862:Bone Resorption / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement; D049109:Cell Proliferation / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D010010:Osteoclasts / Q000187:drug effects*; D010012:Osteogenesis / Q000187:drug effects
D016179:Granulocyte Colony-Stimulating Factor