Bone marrow mesenchymal stem cells express a restricted set of functionally active chemokine receptors capable of promoting migration to pancreatic islets

Valeria Sordi, Maria Luisa Malosio, Federica Marchesi, Alessia Mercalli, Raffaella Melzi, Tiziana Giordano, Nathalie Belmonte, Giuliana Ferrari, Biagio Eugenio Leone, Federico Bertuzzi, Gianpaolo Zerbini, Paola Allavena, Ezio Bonifacio, Lorenzo Piemonti

Research output: Contribution to journalArticle

454 Citations (Scopus)

Abstract

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 (CXC receptor 4 [CXCR4], CX3C receptor 1 [CX3CR1], CXCR6, CC chemokine receptor 1 [CCR1], CCR7) and, accordingly, showed appreciable chemotactic migration in response to the chemokines CXC ligand 12 (CXCL12), CX3CL1, CXCL16, CC chemokine ligand 3 (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 green fluorescent protein (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 that determines their migratory activity. Modulation of homing capacity may be instrumental for harnessing the therapeutic potential of BM-MSCs.

Original languageEnglish
Pages (from-to)419-427
Number of pages9
JournalBlood
Volume106
Issue number2
DOIs
Publication statusPublished - Jul 15 2005

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Chemokine Receptors
Stem cells
Mesenchymal Stromal Cells
Islets of Langerhans
Bone
Bone Marrow
CCR7 Receptors
CCR1 Receptors
Tissue
Ligands
CXCR Receptors
CXCR4 Receptors
CXC Chemokines
CC Chemokines
Stromal Cells
Green Fluorescent Proteins
Pancreas
Modulation
Therapeutics
Population

ASJC Scopus subject areas

  • Hematology

Cite this

Bone marrow mesenchymal stem cells express a restricted set of functionally active chemokine receptors capable of promoting migration to pancreatic islets. / Sordi, Valeria; Malosio, Maria Luisa; Marchesi, Federica; Mercalli, Alessia; Melzi, Raffaella; Giordano, Tiziana; Belmonte, Nathalie; Ferrari, Giuliana; Leone, Biagio Eugenio; Bertuzzi, Federico; Zerbini, Gianpaolo; Allavena, Paola; Bonifacio, Ezio; Piemonti, Lorenzo.

In: Blood, Vol. 106, No. 2, 15.07.2005, p. 419-427.

Research output: Contribution to journalArticle

Sordi, Valeria ; Malosio, Maria Luisa ; Marchesi, Federica ; Mercalli, Alessia ; Melzi, Raffaella ; Giordano, Tiziana ; Belmonte, Nathalie ; Ferrari, Giuliana ; Leone, Biagio Eugenio ; Bertuzzi, Federico ; Zerbini, Gianpaolo ; Allavena, Paola ; Bonifacio, Ezio ; Piemonti, Lorenzo. / Bone marrow mesenchymal stem cells express a restricted set of functionally active chemokine receptors capable of promoting migration to pancreatic islets. In: Blood. 2005 ; Vol. 106, No. 2. pp. 419-427.
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AU - Marchesi, Federica

AU - Mercalli, Alessia

AU - Melzi, Raffaella

AU - Giordano, Tiziana

AU - Belmonte, Nathalie

AU - Ferrari, Giuliana

AU - Leone, Biagio Eugenio

AU - Bertuzzi, Federico

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AU - Bonifacio, Ezio

AU - Piemonti, Lorenzo

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