IFN-Gamma and TNF-Alpha as a Priming Strategy to Enhance the Immunomodulatory Capacity of Secretomes from Menstrual Blood-Derived Stromal Cells
| Autor: | María de Los Ángeles de Pedro, Francisco M. Sánchez-Margallo, Elke Pogge von Strandmann, Verónica Álvarez, Federica Marinaro, Christian Preußer, Javier G. Casado, Esther López, María Gómez-Serrano, María Pulido |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Adult
Stromal cell QH301-705.5 T-Lymphocytes Priming (immunology) Inflammation Catalysis Article Inorganic Chemistry Immunomodulation Extracellular Vesicles Interferon-gamma Immune system medicine Humans Indoleamine-Pyrrole 2 3 -Dioxygenase Interferon gamma Biology (General) Physical and Theoretical Chemistry priming QD1-999 Molecular Biology Spectroscopy Chemistry Tumor Necrosis Factor-alpha Organic Chemistry Mesenchymal stem cell Mesenchymal Stem Cells General Medicine Coculture Techniques Healthy Volunteers Computer Science Applications menstrual blood Menstruation secretome MicroRNAs Gene Expression Regulation Antigens Surface Cancer research Tumor necrosis factor alpha Female medicine.symptom mesenchymal stromal cells CD8 medicine.drug |
| Zdroj: | International Journal of Molecular Sciences International Journal of Molecular Sciences, Vol 22, Iss 12177, p 12177 (2021) Volume 22 Issue 22 |
| ISSN: | 1422-0067 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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