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Mesenchymal and haematopoietic stem cells form a unique bone marrow niche

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  • Simón Méndez-Ferrer

    (Mount Sinai School of Medicine
    Mount Sinai School of Medicine
    Present address: Department of Cardiovascular Developmental Biology, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid 28029, Spain (S.M.-F.); Institute for Life Sciences, University of Southampton, Highfield, Southampton SO17 1BJ, UK (B.D.M.).)

  • Tatyana V. Michurina

    (Cold Spring Harbor Laboratory)

  • Francesca Ferraro

    (Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School)

  • Amin R. Mazloom

    (Mount Sinai School of Medicine)

  • Ben D. MacArthur

    (Mount Sinai School of Medicine
    Present address: Department of Cardiovascular Developmental Biology, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid 28029, Spain (S.M.-F.); Institute for Life Sciences, University of Southampton, Highfield, Southampton SO17 1BJ, UK (B.D.M.).)

  • Sergio A. Lira

    (Mount Sinai School of Medicine)

  • David T. Scadden

    (Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School)

  • Avi Ma’ayan

    (Mount Sinai School of Medicine)

  • Grigori N. Enikolopov

    (Cold Spring Harbor Laboratory)

  • Paul S. Frenette

    (Mount Sinai School of Medicine
    Mount Sinai School of Medicine
    Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine)

Abstract

The cellular constituents forming the haematopoietic stem cell (HSC) niche in the bone marrow are unclear, with studies implicating osteoblasts, endothelial and perivascular cells. Here we demonstrate that mesenchymal stem cells (MSCs), identified using nestin expression, constitute an essential HSC niche component. Nestin+ MSCs contain all the bone-marrow colony-forming-unit fibroblastic activity and can be propagated as non-adherent ‘mesenspheres’ that can self-renew and expand in serial transplantations. Nestin+ MSCs are spatially associated with HSCs and adrenergic nerve fibres, and highly express HSC maintenance genes. These genes, and others triggering osteoblastic differentiation, are selectively downregulated during enforced HSC mobilization or β3 adrenoreceptor activation. Whereas parathormone administration doubles the number of bone marrow nestin+ cells and favours their osteoblastic differentiation, in vivo nestin+ cell depletion rapidly reduces HSC content in the bone marrow. Purified HSCs home near nestin+ MSCs in the bone marrow of lethally irradiated mice, whereas in vivo nestin+ cell depletion significantly reduces bone marrow homing of haematopoietic progenitors. These results uncover an unprecedented partnership between two distinct somatic stem-cell types and are indicative of a unique niche in the bone marrow made of heterotypic stem-cell pairs.

Suggested Citation

  • Simón Méndez-Ferrer & Tatyana V. Michurina & Francesca Ferraro & Amin R. Mazloom & Ben D. MacArthur & Sergio A. Lira & David T. Scadden & Avi Ma’ayan & Grigori N. Enikolopov & Paul S. Frenette, 2010. "Mesenchymal and haematopoietic stem cells form a unique bone marrow niche," Nature, Nature, vol. 466(7308), pages 829-834, August.
    • Handle: RePEc:nat:nature:v:466:y:2010:i:7308:d:10.1038_nature09262
    DOI: 10.1038/nature09262
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