Hematopoietic stem cell mobilizing agents G-CSF, cyclophosphamide or AMD3100 have distinct mechanisms of action on bone marrow HSC niches and bone formation

Winkler, I. G., Pettit, A. R., Raggatt, L. J., Jacobsen, R. N., Forristal, C. E., Barbier, V., Nowlan, B., Cisterne, A., Bendall, L. J., Sims, N. A. and Levesque, J-P. (2012) Hematopoietic stem cell mobilizing agents G-CSF, cyclophosphamide or AMD3100 have distinct mechanisms of action on bone marrow HSC niches and bone formation. Leukemia, 26 7: 1594-1601. doi:10.1038/leu.2012.17


Author Winkler, I. G.
Pettit, A. R.
Raggatt, L. J.
Jacobsen, R. N.
Forristal, C. E.
Barbier, V.
Nowlan, B.
Cisterne, A.
Bendall, L. J.
Sims, N. A.
Levesque, J-P.
Title Hematopoietic stem cell mobilizing agents G-CSF, cyclophosphamide or AMD3100 have distinct mechanisms of action on bone marrow HSC niches and bone formation
Journal name Leukemia   Check publisher's open access policy
ISSN 0887-6924
1476-5551
Publication date 2012-07
Sub-type Article (original research)
DOI 10.1038/leu.2012.17
Open Access Status
Volume 26
Issue 7
Start page 1594
End page 1601
Total pages 8
Place of publication London, United Kingdom
Publisher Nature
Collection year 2013
Language eng
Abstract The CXCR4 antagonist AMD3100 is progressively replacing cyclophosphamide (CYP) as adjuvant to granulocyte colony-stimulating factor (G-CSF) to mobilize hematopoietic stem cells (HSC) for autologous transplants in patients who failed prior mobilization with G-CSF alone. It has recently emerged that G-CSF mediates HSC mobilization and inhibits bone formation via specific bone marrow (BM) macrophages. We compared the effect of these three mobilizing agents on BM macrophages, bone formation, osteoblasts, HSC niches and HSC reconstitution potential. Both G-CSF and CYP suppressed niche-supportive macrophages and osteoblasts, and inhibited expression of endosteal cytokines resulting in major impairment of HSC reconstitution potential remaining in the mobilized BM. In sharp contrast, although AMD3100 was effective at mobilizing HSC, it did not suppress osteoblasts, endosteal cytokine expression or reconstitution potential of HSC remaining in the mobilized BM. In conclusion, although G-CSF, CYP and AMD3100 efficiently mobilize HSC into the blood, their effects on HSC niches and bone formation are distinct with both G-CSF and CYP targeting HSC niche function and bone formation, whereas AMD3100 directly targets HSC without altering niche function or bone formation.
Keyword G-csf
Cyclophosphamide
Amd3100
Mobilization
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online 7 February 2012

 
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