title: The Human Mesenchymal Stromal Cell-Derived Osteocyte Capacity to Modulate Dendritic Cell Functions Is Strictly Dependent on the Culture System.
abstract: In vitro differentiation of mesenchymal stromal cells (MSC) into osteocytes (human differentiated osteogenic cells, hDOC) before implantation has been proposed to optimize bone regeneration. However, a deep characterization of the immunological properties of DOC, including their effect on dendritic cell (DC) function, is not available. DOC can be used either as cellular suspension (detached, Det-DOC) or as adherent cells implanted on scaffolds (adherent, Adh-DOC). By mimicking in vitro these two different routes of administration, we show that both Det-DOC and Adh-DOC can modulate DC functions. Specifically, the weak downregulation of CD80 and CD86 caused by Det-DOC on DC surface results in a weak modulation of DC functions, which indeed retain a high capacity to induce T-cell proliferation and to generate CD4(+)CD25(+)Foxp3(+) T cells. Moreover, Det-DOC enhance the DC capacity to differentiate CD4(+)CD161(+)CD196(+) Th17-cells by upregulating IL-6 secretion. Conversely, Adh-DOC strongly suppress DC functions by a profound downregulation of CD80 and CD86 on DC as well as by the inhibition of TGF-β production. In conclusion, we demonstrate that different types of DOC cell preparation may have a different impact on the modulation of the host immune system. This finding may have relevant implications for the design of cell-based tissue-engineering strategies.
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology "L. & A. Seràgnoli", University of Bologna, 40138 Bologna, Italy ; Ludwig Center for Cancer Research, The University of Lausanne, 1011 Lausanne, Switzerland.
authors.forename: Sara
authors.initials: S
authors.lastname: Trabanelli
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology "L. & A. Seràgnoli", University of Bologna, 40138 Bologna, Italy ; Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, 4714 Meldola, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: La Manna
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology "L. & A. Seràgnoli", University of Bologna, 40138 Bologna, Italy ; MRC Centre for Transplantation, Division of Transplantation Immunology & Mucosal Biology, King's College London, London WC2R 2LS, UK.
authors.forename: Marco
authors.initials: M
authors.lastname: Romano
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology "L. & A. Seràgnoli", University of Bologna, 40138 Bologna, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Salvestrini
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology "L. & A. Seràgnoli", University of Bologna, 40138 Bologna, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Cavo
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology "L. & A. Seràgnoli", University of Bologna, 40138 Bologna, Italy.
authors.forename: Marilena
authors.initials: M
authors.lastname: Ciciarello
authors.affiliation: Department of Internal Medicine (DiMI), University of Genoa and IRCCS Azienda Ospedaliera Universitaria S. Martino-IST, 16132 Genoa, Italy.
authors.forename: Roberto M
authors.initials: RM
authors.lastname: Lemoli
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology "L. & A. Seràgnoli", University of Bologna, 40138 Bologna, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Curti
mesh_terms: D002450:Cell Communication; D002454:Cell Differentiation; D018920:Coculture Techniques; D016207:Cytokines; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D056747:Immunomodulation; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000276:immunology; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D010011:Osteocytes / Q000166:cytology / Q000378:metabolism*; D010641:Phenotype; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines