Mesenchymal Stem/Stromal Cells Derived from Dental Tissues: A Comparative In Vitro Evaluation of Their Immunoregulatory Properties Against T cells

Bone marrow mesenchymal stem/stromal cells (BM-MSCs) have immunoregulatory properties and have been used as immune regulators for the treatment of graft-versus-host disease (GVHD). Human dental tissue mesenchymal stem cells (DT-MSCs) constitute an attractive alternative to BM-MSCs for potential clin...

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Main Authors: María del Pilar De la Rosa-Ruiz, Marco Antonio Álvarez-Pérez, Víctor Adrián Cortés-Morales, Alberto Monroy-García, Héctor Mayani, Gladis Fragoso-González, Sara Caballero-Chacón, Daniel Diaz, Fernando Candanedo-González, Juan José Montesinos
Format: Article
Language:English
Published: MDPI AG 2019-11-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/8/12/1491
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author María del Pilar De la Rosa-Ruiz
Marco Antonio Álvarez-Pérez
Víctor Adrián Cortés-Morales
Alberto Monroy-García
Héctor Mayani
Gladis Fragoso-González
Sara Caballero-Chacón
Daniel Diaz
Fernando Candanedo-González
Juan José Montesinos
author_facet María del Pilar De la Rosa-Ruiz
Marco Antonio Álvarez-Pérez
Víctor Adrián Cortés-Morales
Alberto Monroy-García
Héctor Mayani
Gladis Fragoso-González
Sara Caballero-Chacón
Daniel Diaz
Fernando Candanedo-González
Juan José Montesinos
author_sort María del Pilar De la Rosa-Ruiz
collection DOAJ
description Bone marrow mesenchymal stem/stromal cells (BM-MSCs) have immunoregulatory properties and have been used as immune regulators for the treatment of graft-versus-host disease (GVHD). Human dental tissue mesenchymal stem cells (DT-MSCs) constitute an attractive alternative to BM-MSCs for potential clinical applications because of their accessibility and easy preparation. The aim of this in vitro study was to compare MSCs from dental pulp (DP-MSCs), gingival tissue (G-MSCs), and periodontal ligament (PDL-MSCs) in terms of their immunosuppressive properties against lymphoid cell populations enriched for CD3<sup>+</sup> T cells to determine which MSCs would be the most appropriate for in vivo immunoregulatory applications. BM-MSCs were included as the gold standard. Our results demonstrated, in vitro, that MSCs from DP, G, and PDL showed immunoregulatory properties similar to those from BM, in terms of the cellular proliferation inhibition of both CD4<sup>+</sup>- and CD8<sup>+</sup>-activated T-cells. This reduced proliferation in cell co-cultures correlated with the production of interferon-&#947; and tumor necrosis factor alpha (TNF-&#945;) and the upregulation of programmed death ligand 1 (PD-L1) in MSCs and cytotoxic T-cell-associated Ag-4 (CTLA-4) in T-cells and increased interleukin-10 and prostaglandin E<sub>2</sub> production. Interestingly, we observed differences in the production of cytokines and surface and secreted molecules that may participate in T-cell immunosuppression in co-cultures in the presence of DT-MSCs compared with BM-MSCs. Importantly, MSCs from four sources favored the generation of T-cell subsets displaying the regulatory phenotypes CD4<sup>+</sup>CD25<sup>+</sup>Foxp3<sup>+</sup> and CD4<sup>+</sup>CD25<sup>+</sup>CTLA-4<sup>+</sup>. Our results in vitro indicate that, in addition to BM-MSCs, MSCs from all of the dental sources analyzed in this study might be candidates for future therapeutic applications.
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spelling doaj.art-f4b34242e80d45ccab3a48a3bd65ea282023-09-02T21:16:47ZengMDPI AGCells2073-44092019-11-01812149110.3390/cells8121491cells8121491Mesenchymal Stem/Stromal Cells Derived from Dental Tissues: A Comparative In Vitro Evaluation of Their Immunoregulatory Properties Against T cellsMaría del Pilar De la Rosa-Ruiz0Marco Antonio Álvarez-Pérez1Víctor Adrián Cortés-Morales2Alberto Monroy-García3Héctor Mayani4Gladis Fragoso-González5Sara Caballero-Chacón6Daniel Diaz7Fernando Candanedo-González8Juan José Montesinos9Mesenchymal Stem Cells Laboratory, Oncology Research Unit, Oncology Hospital, National Medical Center (IMSS), POST 06720 Mexico City, MexicoTissue Bioengineering Laboratory, Division of Graduate Studies and Research of the Faculty of Dentistry, National Autonomous University of Mexico (UNAM), 04510 Mexico City, MexicoMesenchymal Stem Cells Laboratory, Oncology Research Unit, Oncology Hospital, National Medical Center (IMSS), POST 06720 Mexico City, MexicoImmunology and Cancer Laboratory; Oncology Research Unit, Oncology Hospital, National Medical Center (IMSS), 06720 Mexico City, MexicoHematopoietic Stem Cells Laboratory, Oncology Research Unit, Oncology Hospital, National Medical Center (IMSS), 06720 Mexico City, MexicoInstitute of Biomedical Research, Immunology Departament, National Autonomous University of Mexico (UNAM), 04510 Mexico City, MexicoDepartment of Physiology and Pharmacology, Faculty of Veterinary Medicine, National Autonomous University of Mexico (UNAM), 04510 Mexico City, MexicoFaculty of Veterinary Medicine, Autonomous University of Sinaloa, Culiacan Rosales, 80246 Sinaloa, MexicoDepartment of Pathology, High Specialty Medical Unit (UMAE), National Medical Center (IMSS), 06720 Mexico City, MexicoMesenchymal Stem Cells Laboratory, Oncology Research Unit, Oncology Hospital, National Medical Center (IMSS), POST 06720 Mexico City, MexicoBone marrow mesenchymal stem/stromal cells (BM-MSCs) have immunoregulatory properties and have been used as immune regulators for the treatment of graft-versus-host disease (GVHD). Human dental tissue mesenchymal stem cells (DT-MSCs) constitute an attractive alternative to BM-MSCs for potential clinical applications because of their accessibility and easy preparation. The aim of this in vitro study was to compare MSCs from dental pulp (DP-MSCs), gingival tissue (G-MSCs), and periodontal ligament (PDL-MSCs) in terms of their immunosuppressive properties against lymphoid cell populations enriched for CD3<sup>+</sup> T cells to determine which MSCs would be the most appropriate for in vivo immunoregulatory applications. BM-MSCs were included as the gold standard. Our results demonstrated, in vitro, that MSCs from DP, G, and PDL showed immunoregulatory properties similar to those from BM, in terms of the cellular proliferation inhibition of both CD4<sup>+</sup>- and CD8<sup>+</sup>-activated T-cells. This reduced proliferation in cell co-cultures correlated with the production of interferon-&#947; and tumor necrosis factor alpha (TNF-&#945;) and the upregulation of programmed death ligand 1 (PD-L1) in MSCs and cytotoxic T-cell-associated Ag-4 (CTLA-4) in T-cells and increased interleukin-10 and prostaglandin E<sub>2</sub> production. Interestingly, we observed differences in the production of cytokines and surface and secreted molecules that may participate in T-cell immunosuppression in co-cultures in the presence of DT-MSCs compared with BM-MSCs. Importantly, MSCs from four sources favored the generation of T-cell subsets displaying the regulatory phenotypes CD4<sup>+</sup>CD25<sup>+</sup>Foxp3<sup>+</sup> and CD4<sup>+</sup>CD25<sup>+</sup>CTLA-4<sup>+</sup>. Our results in vitro indicate that, in addition to BM-MSCs, MSCs from all of the dental sources analyzed in this study might be candidates for future therapeutic applications.https://www.mdpi.com/2073-4409/8/12/1491gingival tissuedental pulpperiodontal ligamentimmunoregulationmesenchymal stem/stromal cellst cells
spellingShingle María del Pilar De la Rosa-Ruiz
Marco Antonio Álvarez-Pérez
Víctor Adrián Cortés-Morales
Alberto Monroy-García
Héctor Mayani
Gladis Fragoso-González
Sara Caballero-Chacón
Daniel Diaz
Fernando Candanedo-González
Juan José Montesinos
Mesenchymal Stem/Stromal Cells Derived from Dental Tissues: A Comparative In Vitro Evaluation of Their Immunoregulatory Properties Against T cells
Cells
gingival tissue
dental pulp
periodontal ligament
immunoregulation
mesenchymal stem/stromal cells
t cells
title Mesenchymal Stem/Stromal Cells Derived from Dental Tissues: A Comparative In Vitro Evaluation of Their Immunoregulatory Properties Against T cells
title_full Mesenchymal Stem/Stromal Cells Derived from Dental Tissues: A Comparative In Vitro Evaluation of Their Immunoregulatory Properties Against T cells
title_fullStr Mesenchymal Stem/Stromal Cells Derived from Dental Tissues: A Comparative In Vitro Evaluation of Their Immunoregulatory Properties Against T cells
title_full_unstemmed Mesenchymal Stem/Stromal Cells Derived from Dental Tissues: A Comparative In Vitro Evaluation of Their Immunoregulatory Properties Against T cells
title_short Mesenchymal Stem/Stromal Cells Derived from Dental Tissues: A Comparative In Vitro Evaluation of Their Immunoregulatory Properties Against T cells
title_sort mesenchymal stem stromal cells derived from dental tissues a comparative in vitro evaluation of their immunoregulatory properties against t cells
topic gingival tissue
dental pulp
periodontal ligament
immunoregulation
mesenchymal stem/stromal cells
t cells
url https://www.mdpi.com/2073-4409/8/12/1491
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