Mesenchymal and haematopoietic stem cells form a unique bone marrow niche

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 and Paul S. Frenette ()
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Simón Méndez-Ferrer: Mount Sinai School of Medicine
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
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

Nature, 2010, vol. 466, issue 7308, 829-834

Abstract: 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.

Date: 2010
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DOI: 10.1038/nature09262

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