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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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	menstrual blood mesenchymal stromal cells secretome priming extracellular vesicles Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/c5f6d5b090f04fb1a9d62a8a5ec93534
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spelling	oai:doaj.org-article:c5f6d5b090f04fb1a9d62a8a5ec935342021-11-25T17:54:07ZIFN-Gamma and TNF-Alpha as a Priming Strategy to Enhance the Immunomodulatory Capacity of Secretomes from Menstrual Blood-Derived Stromal Cells10.3390/ijms2222121771422-00671661-6596https://doaj.org/article/c5f6d5b090f04fb1a9d62a8a5ec935342021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12177https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Mesenchymal 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.María Ángeles de PedroMaría Gómez-SerranoFederica MarinaroEsther LópezMaría PulidoChristian PreußerElke Pogge von StrandmannFrancisco Miguel Sánchez-MargalloVerónica ÁlvarezJavier G. CasadoMDPI AGarticlemenstrual bloodmesenchymal stromal cellssecretomeprimingextracellular vesiclesBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12177, p 12177 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	menstrual blood mesenchymal stromal cells secretome priming extracellular vesicles Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	menstrual blood mesenchymal stromal cells secretome priming extracellular vesicles Biology (General) QH301-705.5 Chemistry QD1-999 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
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.
format	article
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
title	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_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_sort	ifn-gamma and tnf-alpha as a priming strategy to enhance the immunomodulatory capacity of secretomes from menstrual blood-derived stromal cells
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/c5f6d5b090f04fb1a9d62a8a5ec93534
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IFN-Gamma and TNF-Alpha as a Priming Strategy to Enhance the Immunomodulatory Capacity of Secretomes from Menstrual Blood-Derived Stromal Cells

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