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Blood, 15 July 2005, Vol. 106, No. 2, pp. 419-427.
Prepublished online as a Blood First Edition Paper on March 22, 2005; DOI 10.1182/blood-2004-09-3507.
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Submitted September 9, 2004
Accepted March 16, 2005
Bone marrow mesenchymal stem cells express a restricted set of functionally active chemokine receptors capable of promoting migration to pancreatic islets
Valeria Sordi, Maria L Malosio, Federica Marchesi, Alessia Mercalli, Raffaella Melzi, Tiziana Giordano, Nathalie Belmonte, Giuliana Ferrari, Biagio E Leone, Federico Bertuzzi, Gianpaolo Zerbini, Paola Allavena, Ezio Bonifacio, and Lorenzo Piemonti*
Telethon-Juvenile Diabetes Research Foundation Center for Cell Replacement, San Raffaele Scientific Institute, Milan, Italy
Department of Immunology and Cell Biology, Mario Negri Institute, Milan, Italy
H.S. Raffaele-Telethon Institute for Gene Therapy (HSR-TIGET), San Raffaele Scientific Institute, Milan, Italy
Department of Surgery, University of Milano-Bicocca, Milan, Italy
Renal Pathophysiology Laboratory, Division of Medicine, San Raffaele Scientific Institute, Milan, Italy
* Corresponding author; email: piemonti.lorenzo{at}hsr.it.
Bone marrow-derived mesenchymal stem cells (BM-MSCs) are stromal cells with the ability to proliferate and differentiate into many tissues. Although they represent powerful tools for several therapeutic settings, mechanisms regulating their migration to peripheral tissues are still unknown. Here, we report chemokine receptor expression on human BM-MSCs and their role in mediating migration to tissues. A minority of BM-MSCs (2 to 25%) expressed a restricted set of chemokine receptors (CXCR4, CX3CR1, CXCR6, CCR1, CCR7) and, accordingly, showed appreciable chemotactic migration in response to the chemokines CXCL12, CX3CL1, CXCL16, CCL3, and CCL19. Using human pancreatic islets as an in vitro model of peripheral tissue, we showed that islet supernatants released factors able to attract BM-MSCs in vitro, and this attraction was principally mediated by CX3CL1 and CXCL12. Moreover, cells with features of BM-MSCs were detected within the pancreatic islets of mice injected with GFP positive BM. A population of bona fide MSCs that also expressed CXCR4, CXCR6, CCR1, and CCR7 could be isolated from normal adult human pancreas. This study defines the chemokine receptor repertoire of human BM-MSCs which determines their migratory activity. Modulation of homing capacity may be instrumental for harnessing the therapeutic potential of BM-MSCs.

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