IFN-Gamma and TNF-Alpha as a Priming Strategy to Enhance the Immunomodulatory Capacity of Secretomes from Menstrual Blood-Derived Stromal Cells
Mesenchymal stromal cells isolated from menstrual blood (MenSCs) exhibit a potent pro-angiogenic and immunomodulatory capacity. Their therapeutic effect is mediated by paracrine mediators released by their secretomes. In this work, we aimed to evaluate the effect of a specific priming condition on t...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/22/12177 |
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| author | María Ángeles de Pedro María Gómez-Serrano Federica Marinaro Esther López María Pulido Christian Preußer Elke Pogge von Strandmann Francisco Miguel Sánchez-Margallo Verónica Álvarez Javier G. Casado |
| author_facet | María Ángeles de Pedro María Gómez-Serrano Federica Marinaro Esther López María Pulido Christian Preußer Elke Pogge von Strandmann Francisco Miguel Sánchez-Margallo Verónica Álvarez Javier G. Casado |
| author_sort | María Ángeles de Pedro |
| collection | DOAJ |
| description | Mesenchymal stromal cells isolated from menstrual blood (MenSCs) exhibit a potent pro-angiogenic and immunomodulatory capacity. Their therapeutic effect is mediated by paracrine mediators released by their secretomes. In this work, we aimed to evaluate the effect of a specific priming condition on the phenotype and secretome content of MenSCs. Our results revealed that the optimal condition for priming MenSCs was the combination of interferon gamma (IFNγ) and tumor necrosis factor alpha (TNFα) that produced a synergistic and additive effect on IDO1 release and immune-related molecule expression. The analyses of MenSC-derived secretomes after IFNγ and TNFα priming also revealed an increase in EV release and in the differentially expressed miRNAs involved in the immune response and inflammation. Proliferation assays on lymphocyte subsets demonstrated a decrease in CD4+ T cells and CD8+ T cells co-cultured with secretomes, especially in the lymphocytes co-cultured with secretomes from primed cells. Additionally, the expression of immune checkpoints (PD-1 and CTLA-4) was increased in the CD4+ T cells co-cultured with MenSC-derived secretomes. These findings demonstrate that the combination of IFNγ and TNFα represents an excellent priming strategy to enhance the immunomodulatory capacity of MenSCs. Moreover, the secretome derived from primed MenSCs may be postulated as a therapeutic option for the regulation of adverse inflammatory reactions. |
| first_indexed | 2024-03-10T05:26:56Z |
| format | Article |
| id | doaj.art-c5f6d5b090f04fb1a9d62a8a5ec93534 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T05:26:56Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-c5f6d5b090f04fb1a9d62a8a5ec935342023-11-22T23:38:23ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-11-0122221217710.3390/ijms222212177IFN-Gamma and TNF-Alpha as a Priming Strategy to Enhance the Immunomodulatory Capacity of Secretomes from Menstrual Blood-Derived Stromal CellsMaría Ángeles de Pedro0María Gómez-Serrano1Federica Marinaro2Esther López3María Pulido4Christian Preußer5Elke Pogge von Strandmann6Francisco Miguel Sánchez-Margallo7Verónica Álvarez8Javier G. Casado9Stem Cell Therapy Unit, Jesús Usón Minimally Invasive Surgery Centre, 10071 Cáceres, SpainInstitute for Tumor Immunology, Center for Tumor Biology and Immunology (ZTI), Philipps University, 35043 Marburg, GermanyStem Cell Therapy Unit, Jesús Usón Minimally Invasive Surgery Centre, 10071 Cáceres, SpainStem Cell Therapy Unit, Jesús Usón Minimally Invasive Surgery Centre, 10071 Cáceres, SpainStem Cell Therapy Unit, Jesús Usón Minimally Invasive Surgery Centre, 10071 Cáceres, SpainInstitute for Tumor Immunology, Center for Tumor Biology and Immunology (ZTI), Philipps University, 35043 Marburg, GermanyInstitute for Tumor Immunology, Center for Tumor Biology and Immunology (ZTI), Philipps University, 35043 Marburg, GermanyStem Cell Therapy Unit, Jesús Usón Minimally Invasive Surgery Centre, 10071 Cáceres, SpainStem Cell Therapy Unit, Jesús Usón Minimally Invasive Surgery Centre, 10071 Cáceres, SpainCIBER de Enfermedades Cardiovasculares (CIBERCV), 28029 Madrid, SpainMesenchymal stromal cells isolated from menstrual blood (MenSCs) exhibit a potent pro-angiogenic and immunomodulatory capacity. Their therapeutic effect is mediated by paracrine mediators released by their secretomes. In this work, we aimed to evaluate the effect of a specific priming condition on the phenotype and secretome content of MenSCs. Our results revealed that the optimal condition for priming MenSCs was the combination of interferon gamma (IFNγ) and tumor necrosis factor alpha (TNFα) that produced a synergistic and additive effect on IDO1 release and immune-related molecule expression. The analyses of MenSC-derived secretomes after IFNγ and TNFα priming also revealed an increase in EV release and in the differentially expressed miRNAs involved in the immune response and inflammation. Proliferation assays on lymphocyte subsets demonstrated a decrease in CD4+ T cells and CD8+ T cells co-cultured with secretomes, especially in the lymphocytes co-cultured with secretomes from primed cells. Additionally, the expression of immune checkpoints (PD-1 and CTLA-4) was increased in the CD4+ T cells co-cultured with MenSC-derived secretomes. These findings demonstrate that the combination of IFNγ and TNFα represents an excellent priming strategy to enhance the immunomodulatory capacity of MenSCs. Moreover, the secretome derived from primed MenSCs may be postulated as a therapeutic option for the regulation of adverse inflammatory reactions.https://www.mdpi.com/1422-0067/22/22/12177menstrual bloodmesenchymal stromal cellssecretomeprimingextracellular vesicles |
| spellingShingle | María Ángeles de Pedro María Gómez-Serrano Federica Marinaro Esther López María Pulido Christian Preußer Elke Pogge von Strandmann Francisco Miguel Sánchez-Margallo Verónica Álvarez Javier G. Casado IFN-Gamma and TNF-Alpha as a Priming Strategy to Enhance the Immunomodulatory Capacity of Secretomes from Menstrual Blood-Derived Stromal Cells International Journal of Molecular Sciences menstrual blood mesenchymal stromal cells secretome priming extracellular vesicles |
| title | IFN-Gamma and TNF-Alpha as a Priming Strategy to Enhance the Immunomodulatory Capacity of Secretomes from Menstrual Blood-Derived Stromal Cells |
| title_full | IFN-Gamma and TNF-Alpha as a Priming Strategy to Enhance the Immunomodulatory Capacity of Secretomes from Menstrual Blood-Derived Stromal Cells |
| title_fullStr | IFN-Gamma and TNF-Alpha as a Priming Strategy to Enhance the Immunomodulatory Capacity of Secretomes from Menstrual Blood-Derived Stromal Cells |
| title_full_unstemmed | IFN-Gamma and TNF-Alpha as a Priming Strategy to Enhance the Immunomodulatory Capacity of Secretomes from Menstrual Blood-Derived Stromal Cells |
| title_short | IFN-Gamma and TNF-Alpha as a Priming Strategy to Enhance the Immunomodulatory Capacity of Secretomes from Menstrual Blood-Derived Stromal Cells |
| title_sort | ifn gamma and tnf alpha as a priming strategy to enhance the immunomodulatory capacity of secretomes from menstrual blood derived stromal cells |
| topic | menstrual blood mesenchymal stromal cells secretome priming extracellular vesicles |
| url | https://www.mdpi.com/1422-0067/22/22/12177 |
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