Stem Cells
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First published online March 29, 2007
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2007-0054v1
25/7/1737    most recent
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Submitted on January 24, 2007
Accepted on March 20, 2007

Tissue-Specific Stem Cells

The in vitro migration capacity of human bone marrow mesenchymal stem cells: Comparison of chemokine and growth factor chemotactic activities

Adriana López Ponte 1, Emeline Marais 1, Nathalie Gallay 1, Alain Langonné 2, Bruno Delorme 1, Olivier Hérault 3, Pierre Charbord 1, Jorge Domenech 3*

1 Laboratoire d'Hématopoïése, Inserm ERI5 EA3855, IFR135, Université François Rabelais de Tours, Tours, France
2 Laboratoire d'Hématopoïése, Inserm ERI5 EA3855, IFR135, Université François Rabelais de Tours, Tours, France; EFS Centre-Atlantique, Tours, France
3 Laboratoire d'Hématopoïése, Inserm ERI5 EA3855, IFR135, Université François Rabelais de Tours, Tours, France; CHRU de Tours, Tours, France

* To whom correspondence should be addressed. E-mail: domenech{at}med.univ-tours.fr.


  Abstract

Adult bone marrow (BM)-derived stem cells, including hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs), represent an important source of cells for the repair of a number of damaged tissues. In contrast to HSCs, the soluble factors able to induce MSC migration have not been extensively studied. In the present work, we compared the in vitro migration capacity of human BM-derived MSCs, pre-incubated or not with the inflammatory cytokines interleukin 1-beta (IL1{beta}) and tumor-necrosis factor-alpha (TNF{alpha}), in response to 16 growth factors (GFs) and chemokines. We show that BM MSCs migrate in response to many chemotactic factors. The GFs PDGF-AB and IGF-1 are the most potent, while the chemokines RANTES, MDC and SDF-1 have limited effect. Remarkably, pre-incubation with TNF{alpha} leads to increased MSC migration towards chemokines, while migration towards most GFs is unchanged. Consistent with these results, BM MSCs express the tyrosine kinase receptors PDGF-R{alpha}, PDGF-R{beta} and IGF-R, as well as the RANTES and MDC receptors CCR2, CCR3, CCR4 and the SDF-1 receptor CXCR4. TNF{alpha} increases CCR2, CCR3 and CCR4 expression (as opposed to that of CXCR4) together with RANTES membrane binding. These data indicate that the migration capacity of BM MSCs is under the control of a large range of receptor tyrosine kinase GFs and CC and CXC chemokines. Chemokines are mostly more effective on TNF{alpha}-primed cells. Our results suggest that the mobilization of MSCs and their subsequent homing to injured tissues may depend on the systemic and local inflammatory state.

Key Words. Bone marrow, mesenchymal stem cell, in vitro migration, growth factors, chemokines, TNF{alpha}




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