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Menstrual blood-derived stromal cells: insights into their secretome in acute hypoxia conditions

BACKGROUND: Despite constant advances in regenerative medicine, the closure of chronic wounds is still challenging. Therapeutic approaches using locally administered MSCs have been considered a promising option. However, the viability of these cells is seriously threatened by acute hypoxic stress li...

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Autores principales: de Pedro, María Ángeles, Pulido, María, Álvarez, Verónica, Marinaro, Federica, Marchena, Ana María, Sánchez-Margallo, Francisco Miguel, Casado, Javier G., López, Esther
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10074862/
https://www.ncbi.nlm.nih.gov/pubmed/37016307
http://dx.doi.org/10.1186/s10020-023-00646-1
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author de Pedro, María Ángeles
Pulido, María
Álvarez, Verónica
Marinaro, Federica
Marchena, Ana María
Sánchez-Margallo, Francisco Miguel
Casado, Javier G.
López, Esther
author_facet de Pedro, María Ángeles
Pulido, María
Álvarez, Verónica
Marinaro, Federica
Marchena, Ana María
Sánchez-Margallo, Francisco Miguel
Casado, Javier G.
López, Esther
author_sort de Pedro, María Ángeles
collection PubMed
description BACKGROUND: Despite constant advances in regenerative medicine, the closure of chronic wounds is still challenging. Therapeutic approaches using locally administered MSCs have been considered a promising option. However, the viability of these cells is seriously threatened by acute hypoxic stress linked to wound healing. In this work, we aimed to study the tolerance of Menstrual blood-derived stromal cells (MenSCs) to acute hypoxia and their therapeutic paracrine effect. METHODS: Isolated MenSCs were phenotypically characterized and evaluated in terms of proliferation, viability, and gene expression, under acute hypoxia (AH) compared with conventional cultured condition or normoxia (N). A step further, the secretome of MenSCs under acute hypoxia was analyzed with respect to their miRNAs content and by in vitro functional assays. For the analysis of differences between the two groups, Student’s t-test was performed and one-way ANOVA and Tukey’s multiple comparisons test for multiple groups were used. RESULTS: Our results revealed that the viability of MenSCs was not affected under acute hypoxia, although proliferation rate slowed down. Gene analysis revealed 5 up-regulated (BNIP3, ANGPTL4, IL6, IL1B, and PDK1) and 4 down-regulated genes (IDO1, HMOX1, ANGPTL2, and HGF) in AH compared to N. Global gene expression analysis revealed a decrease in the gene ontology functions of migration and wound response with respect to the normoxic condition. In contrast, functions such as angiogenesis were enriched under the AH condition. Regarding the secretome analysis, two miRNAs involved in angiogenic processes (hsa-miR-148a-3p and hsa-miR-378a-3p), were significantly up-expressed when compared to the normoxic condition, being MYC gene, the unique target of both. Functional assays on HUVECs revealed a potential pro-angiogenic capacity of MenSCs cultured in both oxygen conditions (N and AH) based on the wound closure and tube formation results of their released paracrine factors. However, when compared to normoxia, the paracrine factors of MenSCs under acute hypoxia slightly reduced the proliferation, migration, and in vitro wound closure of HUVECs. CONCLUSIONS: MenSC exhibited a good survival capacity under acute hypoxic conditions as well as beneficial properties applicable in the field of tissue regeneration through their secretome, which makes them a potential cell source for wound healing interventions. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s10020-023-00646-1.
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spelling pubmed-100748622023-04-06 Menstrual blood-derived stromal cells: insights into their secretome in acute hypoxia conditions de Pedro, María Ángeles Pulido, María Álvarez, Verónica Marinaro, Federica Marchena, Ana María Sánchez-Margallo, Francisco Miguel Casado, Javier G. López, Esther Mol Med Research Article BACKGROUND: Despite constant advances in regenerative medicine, the closure of chronic wounds is still challenging. Therapeutic approaches using locally administered MSCs have been considered a promising option. However, the viability of these cells is seriously threatened by acute hypoxic stress linked to wound healing. In this work, we aimed to study the tolerance of Menstrual blood-derived stromal cells (MenSCs) to acute hypoxia and their therapeutic paracrine effect. METHODS: Isolated MenSCs were phenotypically characterized and evaluated in terms of proliferation, viability, and gene expression, under acute hypoxia (AH) compared with conventional cultured condition or normoxia (N). A step further, the secretome of MenSCs under acute hypoxia was analyzed with respect to their miRNAs content and by in vitro functional assays. For the analysis of differences between the two groups, Student’s t-test was performed and one-way ANOVA and Tukey’s multiple comparisons test for multiple groups were used. RESULTS: Our results revealed that the viability of MenSCs was not affected under acute hypoxia, although proliferation rate slowed down. Gene analysis revealed 5 up-regulated (BNIP3, ANGPTL4, IL6, IL1B, and PDK1) and 4 down-regulated genes (IDO1, HMOX1, ANGPTL2, and HGF) in AH compared to N. Global gene expression analysis revealed a decrease in the gene ontology functions of migration and wound response with respect to the normoxic condition. In contrast, functions such as angiogenesis were enriched under the AH condition. Regarding the secretome analysis, two miRNAs involved in angiogenic processes (hsa-miR-148a-3p and hsa-miR-378a-3p), were significantly up-expressed when compared to the normoxic condition, being MYC gene, the unique target of both. Functional assays on HUVECs revealed a potential pro-angiogenic capacity of MenSCs cultured in both oxygen conditions (N and AH) based on the wound closure and tube formation results of their released paracrine factors. However, when compared to normoxia, the paracrine factors of MenSCs under acute hypoxia slightly reduced the proliferation, migration, and in vitro wound closure of HUVECs. CONCLUSIONS: MenSC exhibited a good survival capacity under acute hypoxic conditions as well as beneficial properties applicable in the field of tissue regeneration through their secretome, which makes them a potential cell source for wound healing interventions. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s10020-023-00646-1. BioMed Central 2023-04-04 /pmc/articles/PMC10074862/ /pubmed/37016307 http://dx.doi.org/10.1186/s10020-023-00646-1 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
de Pedro, María Ángeles
Pulido, María
Álvarez, Verónica
Marinaro, Federica
Marchena, Ana María
Sánchez-Margallo, Francisco Miguel
Casado, Javier G.
López, Esther
Menstrual blood-derived stromal cells: insights into their secretome in acute hypoxia conditions
title Menstrual blood-derived stromal cells: insights into their secretome in acute hypoxia conditions
title_full Menstrual blood-derived stromal cells: insights into their secretome in acute hypoxia conditions
title_fullStr Menstrual blood-derived stromal cells: insights into their secretome in acute hypoxia conditions
title_full_unstemmed Menstrual blood-derived stromal cells: insights into their secretome in acute hypoxia conditions
title_short Menstrual blood-derived stromal cells: insights into their secretome in acute hypoxia conditions
title_sort menstrual blood-derived stromal cells: insights into their secretome in acute hypoxia conditions
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10074862/
https://www.ncbi.nlm.nih.gov/pubmed/37016307
http://dx.doi.org/10.1186/s10020-023-00646-1
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