In vitro study of matrix metalloproteinase/tissue inhibitor of metalloproteinase production by mesenchymal stromal cells in response to inflammatory cytokines: the role of their migration in injured tissues |
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| Authors: | Tatiana Tondreau Nathalie Meuleman Basile Stamatopoulos Cecile De Bruyn Alain Delforge Marielle Dejeneffe Philippe Martiat Dominique Bron Laurence Lagneaux |
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| Affiliation: | 1. Department of Obstetrics and Gynecology, Inselspital, Bern University Hospital, University of Bern, Switzerland;2. Department of Clinical Research, University of Bern, Switzerland;3. Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University, New Haven, Connecticut, USA;1. Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan;2. Department of Dental Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan;3. Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School, Okayama, Japan;4. Department of Biomaterials, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan;1. Department of Immunology, University College London, Royal Free Hospital NHS Trust, Pond Street, Hampstead NW3 2QG, London;2. Faculty of Sciences, Kingston University, Penrhyn Road, Kingston upon Thames, Surrey, KT1 2EE;3. Department of Haematology, St George''s University of London, Cranmer Terrace SW17 0RE, London |
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| Abstract: | Background aimsThe transmigratory capacity of bone marrow (BM) mesenchymal stromal cells (MSC) through the endothelial cell barrier into various tissues and their differentiation potential makes them ideal candidates for cell therapy. Nevertheless, the mechanisms and agents promoting their migration are not fully understood. We evaluated the effects of several inflammatory cytokines on the migration of BM MSC and matrix metalloproteinase (MMP)/tissue inhibitor of metalloproteinase (TIMP) production.MethodsThe migratory potential of BM MSC was evaluated using a Boyden chamber coated with Matrigel® in the presence and absence of stromal cell-derived (SDF)-1α, platelet-derived growth factor (PDGF)bb, insulin-like growth factor (IGF)-I and interleukin (IL)-6. The ability of inflammatory cytokines to induce MSC migration was tested in presence of their respective Ab or blocking peptide. We used immunofluorescence to check the expression of cytokine receptors, and MMP/TIMP production was analyzed at the protein (human cytokine array, enzyme-linked immunosorbent assay (ELISA), gelatine zymography and Western blot) and mRNA quantitative real-time polymerase chain reaction (qRT-PCR) levels.ResultsWe have demonstrated that inflammatory cytokines promote the migratory capacity of BM MSC according to the expression of their respective receptors. Higher migration through Matrigel was observed in response to IL-6 and PDGFbb. qRT-PCR and cytokine array revealed that migration was the result of the variable level of MMP/TIMP in response to inflammatory stimuli.ConclusionsOur observations suggest that chemokines and cytokines involved in the regulation of the immunity or inflammatory process promote the migration of MSC into BM or damaged tissues. One of the mechanisms used by MSC to promote their migration though the extracellular matrix is modulation of the production of MMP-1, MMP-2, MMP-13, TIMP-1 and TIMP-2. |
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