Cited by 801Hematopoietic Stem Cell TransplantationMesenchymal stem cell researchBone Metabolism and Diseases

Bone marrow macrophages maintain hematopoietic stem cell (HSC) niches and their depletion mobilizes HSCs

Winkler, Ingrid G., Sims, Natalie A., Pettit, Allison R., Barbier, Valérie, Nowlan, Bianca, Helwani, Falak, Poulton, Ingrid J., van Rooijen, Nico +3 more·2010·Blood

Abstract

In the bone marrow, hematopoietic stem cells (HSCs) reside in specific niches near osteoblast-lineage cells at the endosteum. To investigate the regulation of these endosteal niches, we studied the mobilization of HSCs into the bloodstream in response to granulocyte colony-stimulating factor (G-CSF). We report that G-CSF mobilization rapidly depletes endosteal osteoblasts, leading to suppressed endosteal bone formation and decreased expression of factors required for HSC retention and self-renewal. Importantly, G-CSF administration also depleted a population of trophic endosteal macrophages (osteomacs) that support osteoblast function. Osteomac loss, osteoblast suppression, and HSC mobilization occurred concomitantly, suggesting that osteomac loss could disrupt endosteal niches. Indeed, in vivo depletion of macrophages, in either macrophage Fas-induced apoptosis (Mafia) transgenic mice or by administration of clodronate-loaded liposomes to wild-type mice, recapitulated the: (1) loss of endosteal osteoblasts and (2) marked reduction of HSC-trophic cytokines at the endosteum, with (3) HSC mobilization into the blood, as observed during G-CSF administration. Together, these results establish that bone marrow macrophages are pivotal to maintain the endosteal HSC niche and that the loss of such macrophages leads to the egress of HSCs into the blood.

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Crossref · 10.1182/blood-2009-11-253534

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  • Macrophages regulate HSPCs indirectly through interaction with MSCs.

    “Previous studies demonstrated that macrophages regulate HSPCs indirectly through interaction with MSCs.82”

    From Inflammatory bone marrow microenvironment (2019) · cites this paper as [82]

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Authors
Winkler, I. G., Sims, N. A., Pettit, A. R., Barbier, V., Nowlan, B., Helwani, F., Poulton, I. J., van Rooijen, N., Alexander, K. A., Raggatt, L. J., & Lévesque, J.-P.
Affiliations
  • Mater Research (AU)
  • The University of Melbourne (AU)
  • The University of Queensland (AU)
  • Department of Molecular Cell Biology, Vrije Universiteit, Amsterdam, The Netherlands; and
Corresponding author
  • Winkler, Ingrid G.
  • Sims, Natalie A.
  • Pettit, Allison R.
  • Raggatt, Liza J.
  • Lévesque, Jean-Pierre
Venue
Blood
Published
2010-12-02
Volume
116
Issue
23
Pages
4815-4828
ISSN
  • 0006-4971 (ISSN-L)
  • 1528-0020
OpenAlex
W2109525494
Cited by
801
References
50
Citations by year
2026: 15 · 2025: 21 · 2024: 40 · 2023: 39 · 2022: 39 · 2021: 68 · 2020: 70 · 2019: 61 · 2018: 58 · 2017: 67 · 2016: 49 · 2015: 60 · 2014: 64 · 2013: 45 · 2012: 60
FWCI
29.83
Type
journal article
Language
en
Open access
closed
Locations
  • Blood (publishedVersion)
  • PubMed (publishedVersion)
  • Pure Amsterdam UMC (publishedVersion)
  • Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
Topics
  • Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
Keywords
hematopoietic stem cells, HSC niche, bone marrow-derived macrophages, endosteal niche, osteoblasts, G-CSF mobilization, hematopoietic stem cell mobilization, osteoblast activity, bone formation, HSC self-renewal, macrophage depletion, clodronate liposomes
MeSH terms
Animals, Bone Marrow Cells, Cell Differentiation, Cell Movement, Cell Separation, Flow Cytometry, Hematopoietic Stem Cells, Immunohistochemistry, Macrophages, Mice, Inbred C57BL, Granulocyte Colony-Stimulating Factor, Mice, Knockout, Cell Lineage, Reverse Transcriptase Polymerase Chain Reaction, Mice, Stem Cell Niche

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