Human Bone Marrow Mesenchymal Stromal/Stem Cells Regulate the Proinflammatory Response of Monocytes and Myeloid Dendritic Cells from Patients with Rheumatoid Arthritis
Rheumatoid arthritis (RA) is a disabling autoimmune disease whose treatment is ineffective for one-third of patients. Thus, the immunomodulatory potential of mesenchymal stromal/stem cells (MSCs) makes MSC-based therapy a promising approach to RA. This study aimed to explore the immunomodulatory act...
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MDPI AG
2022-02-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/2/404 |
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| author | Paula Laranjeira Mónia Pedrosa Cátia Duarte Susana Pedreiro Brígida Antunes Tânia Ribeiro Francisco dos Santos António Martinho Margarida Fardilha M. Rosário Domingues Manuel Abecasis José António Pereira da Silva Artur Paiva |
| author_facet | Paula Laranjeira Mónia Pedrosa Cátia Duarte Susana Pedreiro Brígida Antunes Tânia Ribeiro Francisco dos Santos António Martinho Margarida Fardilha M. Rosário Domingues Manuel Abecasis José António Pereira da Silva Artur Paiva |
| author_sort | Paula Laranjeira |
| collection | DOAJ |
| description | Rheumatoid arthritis (RA) is a disabling autoimmune disease whose treatment is ineffective for one-third of patients. Thus, the immunomodulatory potential of mesenchymal stromal/stem cells (MSCs) makes MSC-based therapy a promising approach to RA. This study aimed to explore the immunomodulatory action of human bone marrow (BM)-MSCs on myeloid dendritic cells (mDCs) and monocytes, especially on cytokines/chemokines involved in RA physiopathology. For that, LPS plus IFNγ-stimulated peripheral blood mononuclear cells from RA patients (n = 12) and healthy individuals (n = 6) were co-cultured with allogeneic BM-MSCs. TNF-α, CD83, CCR7 and MIP-1β protein levels were assessed in mDCs, classical, intermediate, and non-classical monocytes. mRNA expression of other cytokines/chemokines was also evaluated. BM-MSCs effectively reduced TNF-α, CD83, CCR7 and MIP-1β protein levels in mDCs and all monocyte subsets, in RA patients. The inhibition of TNF-α production was mainly achieved by the reduction of the percentage of cellsproducing this cytokine. BM-MSCs exhibited a remarkable suppressive action over antigen-presenting cells from RA patients, potentially affecting their ability to stimulate the immune adaptive response at different levels, by hampering their migration to the lymph node and the production of proinflammatory cytokines and chemokines. Accordingly, MSC-based therapies can be a valuable approach for RA treatment, especially for non-responder patients. |
| first_indexed | 2024-03-09T21:13:58Z |
| format | Article |
| id | doaj.art-68c52330462d417c867dcf4c7f176b49 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T21:13:58Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-68c52330462d417c867dcf4c7f176b492023-11-23T21:38:47ZengMDPI AGPharmaceutics1999-49232022-02-0114240410.3390/pharmaceutics14020404Human Bone Marrow Mesenchymal Stromal/Stem Cells Regulate the Proinflammatory Response of Monocytes and Myeloid Dendritic Cells from Patients with Rheumatoid ArthritisPaula Laranjeira0Mónia Pedrosa1Cátia Duarte2Susana Pedreiro3Brígida Antunes4Tânia Ribeiro5Francisco dos Santos6António Martinho7Margarida Fardilha8M. Rosário Domingues9Manuel Abecasis10José António Pereira da Silva11Artur Paiva12Flow Cytometry Unit, Department of Clinical Pathology, Centro Hospitalar e Universitário de Coimbra, Av. Bissaya Barreto, Bloco de Celas, 3000-075 Coimbra, PortugalCentro do Sangue e da Transplantação de Coimbra, Instituto Português do Sangue e da Transplantação, Coimbra, Portugal, Quinta da Vinha Moura, São Martinho do Bispo, 3041-861 Coimbra, PortugalCoimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, PortugalCentro do Sangue e da Transplantação de Coimbra, Instituto Português do Sangue e da Transplantação, Coimbra, Portugal, Quinta da Vinha Moura, São Martinho do Bispo, 3041-861 Coimbra, PortugalCell2B Advanced Therapeutics, SA, Biocant Park, Núcleo 04, Lote 4A, 3060-197 Cantanhede, PortugalCell2B Advanced Therapeutics, SA, Biocant Park, Núcleo 04, Lote 4A, 3060-197 Cantanhede, PortugalCell2B Advanced Therapeutics, SA, Biocant Park, Núcleo 04, Lote 4A, 3060-197 Cantanhede, PortugalCentro do Sangue e da Transplantação de Coimbra, Instituto Português do Sangue e da Transplantação, Coimbra, Portugal, Quinta da Vinha Moura, São Martinho do Bispo, 3041-861 Coimbra, PortugalSignal Transduction Laboratory, Center of Cellular Biology, SACS and Department of Biology, University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, PortugalMass Spectrometry Centre, LAQV REQUIMTE, Department of Chemistry, University of Aveiro, Santiago University Campus, 3810-193 Aveiro, PortugalServiço de Transplantação de Progenitores Hematopoiéticos (UTM), Instituto Português de Oncologia de Lisboa Francisco Gentil, Rua Professor Lima Basto, 1099-023 Lisbon, PortugalCoimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, PortugalFlow Cytometry Unit, Department of Clinical Pathology, Centro Hospitalar e Universitário de Coimbra, Av. Bissaya Barreto, Bloco de Celas, 3000-075 Coimbra, PortugalRheumatoid arthritis (RA) is a disabling autoimmune disease whose treatment is ineffective for one-third of patients. Thus, the immunomodulatory potential of mesenchymal stromal/stem cells (MSCs) makes MSC-based therapy a promising approach to RA. This study aimed to explore the immunomodulatory action of human bone marrow (BM)-MSCs on myeloid dendritic cells (mDCs) and monocytes, especially on cytokines/chemokines involved in RA physiopathology. For that, LPS plus IFNγ-stimulated peripheral blood mononuclear cells from RA patients (n = 12) and healthy individuals (n = 6) were co-cultured with allogeneic BM-MSCs. TNF-α, CD83, CCR7 and MIP-1β protein levels were assessed in mDCs, classical, intermediate, and non-classical monocytes. mRNA expression of other cytokines/chemokines was also evaluated. BM-MSCs effectively reduced TNF-α, CD83, CCR7 and MIP-1β protein levels in mDCs and all monocyte subsets, in RA patients. The inhibition of TNF-α production was mainly achieved by the reduction of the percentage of cellsproducing this cytokine. BM-MSCs exhibited a remarkable suppressive action over antigen-presenting cells from RA patients, potentially affecting their ability to stimulate the immune adaptive response at different levels, by hampering their migration to the lymph node and the production of proinflammatory cytokines and chemokines. Accordingly, MSC-based therapies can be a valuable approach for RA treatment, especially for non-responder patients.https://www.mdpi.com/1999-4923/14/2/404mesenchymal stromal cellsmesenchymal stem cellsimmunomodulationrheumatoid arthritisdendritic cellsmonocytes |
| spellingShingle | Paula Laranjeira Mónia Pedrosa Cátia Duarte Susana Pedreiro Brígida Antunes Tânia Ribeiro Francisco dos Santos António Martinho Margarida Fardilha M. Rosário Domingues Manuel Abecasis José António Pereira da Silva Artur Paiva Human Bone Marrow Mesenchymal Stromal/Stem Cells Regulate the Proinflammatory Response of Monocytes and Myeloid Dendritic Cells from Patients with Rheumatoid Arthritis Pharmaceutics mesenchymal stromal cells mesenchymal stem cells immunomodulation rheumatoid arthritis dendritic cells monocytes |
| title | Human Bone Marrow Mesenchymal Stromal/Stem Cells Regulate the Proinflammatory Response of Monocytes and Myeloid Dendritic Cells from Patients with Rheumatoid Arthritis |
| title_full | Human Bone Marrow Mesenchymal Stromal/Stem Cells Regulate the Proinflammatory Response of Monocytes and Myeloid Dendritic Cells from Patients with Rheumatoid Arthritis |
| title_fullStr | Human Bone Marrow Mesenchymal Stromal/Stem Cells Regulate the Proinflammatory Response of Monocytes and Myeloid Dendritic Cells from Patients with Rheumatoid Arthritis |
| title_full_unstemmed | Human Bone Marrow Mesenchymal Stromal/Stem Cells Regulate the Proinflammatory Response of Monocytes and Myeloid Dendritic Cells from Patients with Rheumatoid Arthritis |
| title_short | Human Bone Marrow Mesenchymal Stromal/Stem Cells Regulate the Proinflammatory Response of Monocytes and Myeloid Dendritic Cells from Patients with Rheumatoid Arthritis |
| title_sort | human bone marrow mesenchymal stromal stem cells regulate the proinflammatory response of monocytes and myeloid dendritic cells from patients with rheumatoid arthritis |
| topic | mesenchymal stromal cells mesenchymal stem cells immunomodulation rheumatoid arthritis dendritic cells monocytes |
| url | https://www.mdpi.com/1999-4923/14/2/404 |
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