H2O2-preconditioned human adipose-derived stem cells (HC016) increase theirresistance to oxidative stress byoverexpressing Nrf2 and bioenergetic adaptation
dc.contributor.author | Garrido Pascual, Patricia | |
dc.contributor.author | Alonso Varona, Ana Isabel | |
dc.contributor.author | Castro Feo, María Begoña | |
dc.contributor.author | Burón Aizpiri, María | |
dc.contributor.author | Palomares Casado, Teodoro | |
dc.date.accessioned | 2021-01-22T12:23:32Z | |
dc.date.available | 2021-01-22T12:23:32Z | |
dc.date.issued | 2020-08-03 | |
dc.identifier.citation | Stem Cell Research & Therapy 11(1) : (2020) // Article ID 335 | es_ES |
dc.identifier.issn | 1757-6512 | |
dc.identifier.uri | http://hdl.handle.net/10810/49838 | |
dc.description.abstract | BackgroundMesenchymal stem cells, including those derived from human adipose tissue (hASCs), are currently being widely investigated for cell therapy. However, when transplanted at the site of injury, the survival and engraftment rates of hASCs are low, mainly due to the harsh microenvironment they encounter, characterized by inflammation and oxidative stress. To overcome these therapeutic limitations, cell preconditioning with low-concentration of hydrogen peroxide (H2O2) has been proposed as a plausible strategy to increase their survival and adaptation to oxidative stress. Nonetheless, the underlying mechanisms of this approach are not yet fully understood. In this study, we analyzed molecular and bioenergetic changes that take place in H2O2 preconditioned hASCs.MethodsLong-term exposure to a low concentration of H2O2 was applied to obtain preconditioned hASCs (named HC016), and then, their response to oxidative stress was analyzed. The effect of preconditioning on the expression of Nrf2 and its downstream antioxidant enzymes (HO-1, SOD-1, GPx-1, and CAT), and of NF-kappa B and its related inflammatory proteins (COX-2 and IL-1 beta), were examined by Western blot. Finally, the Seahorse XF96 Flux analysis system was used to evaluate the mitochondrial respiration and glycolytic function, along with the total ATP production.ResultsWe found that under oxidative conditions, HC016 cells increased the survival by (i) decreasing intracellular ROS levels through the overexpression of the transcription factor Nrf2 and its related antioxidant enzymes HO-1, SOD-1, GPx-1, and CAT; (ii) reducing the secretion of pro-inflammatory molecules COX-2 and IL-1 beta through the attenuation of the expression of NF-kappa B; and (iii) increasing the total ATP production rate through the adaption of their metabolism to meet the energetic demand required to survive.ConclusionsH(2)O(2) preconditioning enhances hASC survival under oxidative stress conditions by stimulating their antioxidant response and bioenergetic adaptation. Therefore, this preconditioning strategy might be considered an excellent tool for strengthening the resistance of hASCs to harmful oxidative stress. | es_ES |
dc.description.sponsorship | Partial funding for this project was provided by the Department of Economic Development and Competitiveness of the Basque Government, the European Regional Development Fund (PREMISE IG-2015/0000558), and the University of the Basque Country (UPV/EHU; research grants PES 17/29 and 16/37). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Biomed Central | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
dc.subject | human adipose-derived stem cells | es_ES |
dc.subject | H2O2 preconditioning | es_ES |
dc.subject | oxidative stress | es_ES |
dc.subject | Nrf2 | es_ES |
dc.subject | bioenergetic | es_ES |
dc.subject | cell therapy | es_ES |
dc.subject | mitochondrial complex-III | es_ES |
dc.subject | NF-KAPPA-B | es_ES |
dc.subject | in-vitro | es_ES |
dc.subject | signaling pathway | es_ES |
dc.subject | hypoxia | es_ES |
dc.subject | inflammation | es_ES |
dc.subject | metabolism | es_ES |
dc.subject | activation | es_ES |
dc.subject | activation | es_ES |
dc.subject | protection | es_ES |
dc.subject | system | es_ES |
dc.title | H2O2-preconditioned human adipose-derived stem cells (HC016) increase theirresistance to oxidative stress byoverexpressing Nrf2 and bioenergetic adaptation | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.holder | This 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/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. | es_ES |
dc.rights.holder | Atribución 3.0 España | * |
dc.relation.publisherversion | https://stemcellres.biomedcentral.com/articles/10.1186/s13287-020-01851-z | es_ES |
dc.identifier.doi | 10.1186/s13287-020-01851-z | |
dc.departamentoes | Biología celular e histología | es_ES |
dc.departamentoeu | Zelulen biologia eta histologia | es_ES |
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