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TISSUE-SPECIFIC STEM CELLS

The In Vitro Migration Capacity of Human Bone Marrow Mesenchymal Stem Cells: Comparison of Chemokine and Growth Factor Chemotactic Activities

^aLaboratoire d'Hématopoïèse, Institut National de la Santé et de la Recherche Médicale ERI5, IFR135 Université François Rabelais, Tours, France;
^bEFS Centre-Atlantique, Tours, France;
^cCHRU de Tours, Tours, France

Key Words. Bone marrow • Mesenchymal stem cell • In vitro migration • Growth factors • Chemokines • Tumor necrosis factor

Correspondence: Jorge Domenech M.D., Ph.D., Laboratoire d'Hématopoïèse, Inserm-ESPRI-EA3855, Faculté de Médecine, 10 boulevard Tonnellé, 37 032 Tours Cedex, France. Telephone: 33-247-47-47-21; Fax: 33-247-47-69-34; e-mail: domenech{at}med.univ-tours.fr

Received on January 24, 2007; accepted for publication on March 20, 2007.

First published online in STEM CELLS EXPRESS  March 29, 2007.


Adult bone marrow (BM)-derived stem cells, including hematopoietic stem cells (HSCs) and 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, preincubated or not with the inflammatory cytokines interleukin 1ß (IL1ß) and tumor necrosis factor (TNF), in response to 16 growth factors (GFs) and chemokines. We show that BM MSCs migrate in response to many chemotactic factors. The GFs platelet-derived growth factor-AB (PDGF-AB) and insulin-like growth factor 1 (IGF-1) are the most potent, whereas the chemokines RANTES, macrophage-derived chemokine (MDC), and stromal-derived factor-1 (SDF-1) have limited effect. Remarkably, preincubation with TNF leads to increased MSC migration toward chemokines, whereas migration toward most GFs is unchanged. Consistent with these results, BM MSCs express the tyrosine kinase receptors PDGF-receptor (R) , PDGF-Rß, and IGF-R, as well as the RANTES and MDC receptors CCR2, CCR3, and CCR4 and the SDF-1 receptor CXCR4. TNF 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. Most chemokines are more effective on TNF-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.

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

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