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Published on: March 18, 2019
G-CSF increases mesenchymal precursor cell numbers in the bone marrow via an indirect mechanism involving
Nathalie Brouard1, Rebecca Driessen, Brenton Short
1Center 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
Abstract:
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.
Insights
Granulocyte-colony stimulating factor (G-CSF) increases myeloid progenitor cells (MPC) in bone marrow, not circulation. This expansion is linked to G-CSF-induced bone resorption, offering potential for clinical applications.
Area of Science:
- Hematology
- Stem Cell Biology
- Bone Biology
Background:
- Granulocyte-colony stimulating factor (G-CSF) is widely used for hematopoietic stem cell mobilization.
- The effect of G-CSF on myeloid progenitor cells (MPC) in circulation and bone marrow remains incompletely understood.
Purpose of the Study:
- To investigate whether G-CSF influences the number of MPC in circulation and bone marrow.
- To elucidate the mechanism behind G-CSF-induced changes in MPC numbers.
Main Methods:
- Assessed fibroblast colony-forming cells (CFU-F) in vitro to quantify MPC.
- Administered G-CSF to mice and analyzed bone marrow (BM) and blood.
- Utilized hydroxyurea to assess CFU-F proliferation.
- Administered osteoprotegerin (OPG), an osteoclast inhibitor, to investigate the role of bone resorption.
Main Results:
- G-CSF did not increase circulating MPC (CFU-F) but significantly increased BM CFU-F in a time-dependent manner, peaking at Day 7.
- Hydroxyurea treatment did not affect CFU-F numbers, indicating proliferation is not the primary mechanism for expansion.
- OPG administration blocked the G-CSF-induced increase in BM CFU-F, supporting the role of bone resorption.
Conclusions:
- G-CSF administration leads to an expansion of MPC within the bone marrow, not in circulation.
- This expansion is mediated by G-CSF-induced bone resorption.
- G-CSF's ability to expand MPC in vivo presents a potential clinical strategy for cell expansion.
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