The Human Mesenchymal Stromal Cell-Derived Osteocyte Capacity to Modulate Dendritic Cell Functions Is Strictly Dependent on the Culture System

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...

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Main Authors: Sara Trabanelli, Federico La Manna, Marco Romano, Valentina Salvestrini, Michele Cavo, Marilena Ciciarello, Roberto M. Lemoli, Antonio Curti
Format: Article
Language:English
Published: Wiley 2015-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2015/526195
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author Sara Trabanelli
Federico La Manna
Marco Romano
Valentina Salvestrini
Michele Cavo
Marilena Ciciarello
Roberto M. Lemoli
Antonio Curti
author_facet Sara Trabanelli
Federico La Manna
Marco Romano
Valentina Salvestrini
Michele Cavo
Marilena Ciciarello
Roberto M. Lemoli
Antonio Curti
author_sort Sara Trabanelli
collection DOAJ
description 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.
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spelling doaj-art-fbf31d21ba6249bf9da157d7b94844ad2025-02-03T05:51:29ZengWileyJournal of Immunology Research2314-88612314-71562015-01-01201510.1155/2015/526195526195The Human Mesenchymal Stromal Cell-Derived Osteocyte Capacity to Modulate Dendritic Cell Functions Is Strictly Dependent on the Culture SystemSara Trabanelli0Federico La Manna1Marco Romano2Valentina Salvestrini3Michele Cavo4Marilena Ciciarello5Roberto M. Lemoli6Antonio Curti7Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology “L. & A. Seràgnoli”, University of Bologna, 40138 Bologna, ItalyDepartment of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology “L. & A. Seràgnoli”, University of Bologna, 40138 Bologna, ItalyDepartment of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology “L. & A. Seràgnoli”, University of Bologna, 40138 Bologna, ItalyDepartment of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology “L. & A. Seràgnoli”, University of Bologna, 40138 Bologna, ItalyDepartment of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology “L. & A. Seràgnoli”, University of Bologna, 40138 Bologna, ItalyDepartment of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology “L. & A. Seràgnoli”, University of Bologna, 40138 Bologna, ItalyDepartment of Internal Medicine (DiMI), University of Genoa and IRCCS Azienda Ospedaliera Universitaria S. Martino-IST, 16132 Genoa, ItalyDepartment of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology “L. & A. Seràgnoli”, University of Bologna, 40138 Bologna, ItalyIn 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.http://dx.doi.org/10.1155/2015/526195
spellingShingle Sara Trabanelli
Federico La Manna
Marco Romano
Valentina Salvestrini
Michele Cavo
Marilena Ciciarello
Roberto M. Lemoli
Antonio Curti
The Human Mesenchymal Stromal Cell-Derived Osteocyte Capacity to Modulate Dendritic Cell Functions Is Strictly Dependent on the Culture System
Journal of Immunology Research
title The Human Mesenchymal Stromal Cell-Derived Osteocyte Capacity to Modulate Dendritic Cell Functions Is Strictly Dependent on the Culture System
title_full The Human Mesenchymal Stromal Cell-Derived Osteocyte Capacity to Modulate Dendritic Cell Functions Is Strictly Dependent on the Culture System
title_fullStr The Human Mesenchymal Stromal Cell-Derived Osteocyte Capacity to Modulate Dendritic Cell Functions Is Strictly Dependent on the Culture System
title_full_unstemmed The Human Mesenchymal Stromal Cell-Derived Osteocyte Capacity to Modulate Dendritic Cell Functions Is Strictly Dependent on the Culture System
title_short The Human Mesenchymal Stromal Cell-Derived Osteocyte Capacity to Modulate Dendritic Cell Functions Is Strictly Dependent on the Culture System
title_sort human mesenchymal stromal cell derived osteocyte capacity to modulate dendritic cell functions is strictly dependent on the culture system
url http://dx.doi.org/10.1155/2015/526195
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