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 ofCD80 andCD86 caused byDet-DOConDCsurface results in a weakmodulation ofDCfunctions,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- 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.
The Human Mesenchymal Stromal Cell-Derived Osteocyte Capacity to Modulate Dendritic Cell Functions Is Strictly Dependent on the Culture System
ROMANO, MARCO;LEMOLI, ROBERTO MASSIMO;
2015-01-01
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 ofCD80 andCD86 caused byDet-DOConDCsurface results in a weakmodulation ofDCfunctions,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- 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.File | Dimensione | Formato | |
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