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THE STEM CELL NICHE

Human Bone Marrow Adipocytes Block Granulopoiesis Through Neuropilin-1-Induced Granulocyte Colony-Stimulating Factor Inhibition

Departments of ^aCytology and Histology and
^bPathological Anatomy (Groupe Interdisciplinaire de Génoprotéomique Appliquée-Recherche), University of Liege, Belgium;
^cCentre National de la Recherche Scientifique-Unité Mixte de Recherche, Université Paris V. René Descartes,
^gLaboratory of Hematology, Université Paris V. René Descartes, Assistance Publique-Hôpitaux de Paris, and
ⁱDepartment of Clinical Hematology, Université Paris V. René Descartes, Assistance Publique-Hôpitaux de Paris, Hôpital Necker, Paris, France;
^dService de Biochimie et Hormonologie, Hôpital Tenon, Paris, France;
Laboratories of ^eHematobiology and Immunohematology (Groupe Interdisciplinaire de Génoprotéomique Appliquée-Recherche) and
^fConnective Tissue Biology (Groupe Interdisciplinaire de Génoprotéomique Appliquée-Recherche), University of Liege, Liège, Belgium

Key Words. Adult human bone marrow • Granulopoiesis • Stem cell-microenvironment interactions • Bone marrow stromal cells • In vitro differentiation • Bone marrow adipocytes • Neuropilin-1 • Macrophages

Correspondence: Correspondence: Marie Paule Defresne, M.D., Ph.D., Department of Cytology and Histology (Groupe Interdisciplinaire de Génoprotéomique Appliquée-Recherche), University of Liege, CHU-B23, 4000 Liège, Belgium. Telephone: 32-4-366-29-19; Fax: 32-4-366-29-19; e-mail: mp.defresne{at}ulg.ac.be; or Olivier Hermine, M.D., Ph.D., Centre National de la Recherche Scientifique-Unité Mixte de Recherche 8147, Université Paris V. René Descartes, Hôpital Necker, 161 rue de Sèvres, 75015 Paris, France. Telephone: 0033144490675; Fax: 0033144490676; e-mail: hermine{at}necker.fr

Received on January 22, 2008; accepted for publication on March 24, 2008.

First published online in STEM CELLS EXPRESS  April 3, 2008.

Adipocytes are part of hematopoietic microenvironment, even though up to now in humans, their role in hematopoiesis is still questioned. We have previously shown that accumulation of fat cells in femoral bone marrow (BM) coincides with increased expression of neuropilin-1 (NP-1), while it is weakly expressed in hematopoietic iliac crest BM. Starting from this observation, we postulated that adipocytes might exert a negative effect on hematopoiesis mediated through NP-1. To test this hypothesis, we set up BM adipocytes differentiated into fibroblast-like fat cells (FLFC), which share the major characteristics of primitive unilocular fat cells, as an experimental model. As expected, FLFCs constitutively produced macrophage colony stimulating factor and induced CD34⁺ differentiation into macrophages independently of cell-to-cell contact. By contrast, granulopoiesis was hampered by cell-to-cell contact but could be restored in transwell culture conditions, together with granulocyte colony stimulating factor production. Both functions were also recovered when FLFCs cultured in contact with CD34⁺ cells were treated with an antibody neutralizing NP-1, which proved its critical implication in contact inhibition. An inflammatory cytokine such as interleukin-1 β or dexamethasone modulates FLFC properties to restore granulopoiesis. Our data provide the first evidence that primary adipocytes exert regulatory functions during hematopoiesis that might be implicated in some pathological processes.

Disclosure of potential conflicts of interest is found at the end of this article.