5-Azacytidine restores interleukin 6-increased production in mesenchymal stromal cells from myelodysplastic patients
| Autor: | Cristina Touriño, L. Echarte, Lilián Díaz, Matilde Boada, Sofía Grille, Cecilia Guillermo |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Stromal cell
medicine.medical_treatment Myelodysplastic syndromes Mesenchymal stromal cells Proinflammatory cytokine hemic and lymphatic diseases medicine Immunology and Allergy Interferon gamma Interleukin 6 Azacytidine biology business.industry lcsh:RC633-647.5 Mesenchymal stem cell Hematology lcsh:Diseases of the blood and blood-forming organs Inflammatory cytokines Cytokine medicine.anatomical_structure Cancer research biology.protein Original Article Bone marrow Stem cell business medicine.drug |
| Zdroj: | Hematology, Transfusion and Cell Therapy Hematology, Transfusion and Cell Therapy, Vol 43, Iss 1, Pp 35-42 (2021) Hematology, Transfusion and Cell Therapy, Volume: 43, Issue: 1, Pages: 35-42, Published: 26 MAR 2021 |
| ISSN: | 2531-1387 2531-1379 |
| Popis: | Introduction Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematological diseases. In addition to defects in hematologic progenitor and stem cells, dysfunctions in the bone marrow microenvironment (BMM) participate in the MDS pathogenesis. Furthermore, the immune response is deregulated by the pro-inflammatory response prevailing in low-risk MDS, while immunosuppression predominates in high-risk MDS. Mesenchymal stromal cells (MSC), part of the BMM, are characterized by plastic adherent growth and multipotentiality. They exhibit immunomodulatory properties and sustain hematopoiesis. There is conflicting evidence regarding their status in MDS. The aim of this study was to characterize MDS-MSC and evaluate the effect of 5-Azacytidine. Methods The MSC from MDS patients and controls were cultured and characterized according to the International Society of Cell Therapy recommendations. Immunomodulatory properties were assessed by studying the MSD cytokine production, using the cytometric bead array. We evaluated the effect of 5-Azacytidine on the MSC cytokine production. Results We included 35 MDS patients and 22 controls. The MSC from patients and controls were cultured and characterized. The MSC from patients showed morphological differences, but there were no differences in immunophenotype or multipotentiality. The interleukin 6 (IL-6) was the main MSC secreted cytokine. The MDS-MSC produced higher levels of IL-6, IL-17, interferon gamma, or interferon γ (INF-γ), and tumor necrosis factor alpha (TNF-α). The in vitro 5-Azacytidine treatment induced a significant decrease in the IL-6 production by MDS-MSC. Conclusions The MDS-MSC show an increased production of pro-inflammatory cytokines. The in vitro treatment with 5-Azacytidine lead to a significant reduction in the IL-6 production by the MDS-MSC, restoring the IL-6 levels to those found in controls. The MSC produced inflammatory cytokines involved in the MDS pathogenesis, representing a potential future therapeutic target. Moreover, 5-Azacytidine may have a stromal effect, modulating the immune response in MDS. |
| Databáze: | OpenAIRE |
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