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The Antioxidant TEMPOL Protects Human Hematopoietic Stem Cells From Culture-Mediated Loss of Functions

In a steady state, hematopoietic stem cells (HSC) exhibit very low levels of reactive oxygen species (ROS). Upon stress, HSC get activated and enter into proliferation and differentiation process to ensure blood cell regeneration. Once activated, their levels of ROS increase, as messengers to mediat...

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Autores principales: Henry, Elia, Picou, Frédéric, Barroca, Vilma, Dechamps, Nathalie, Sobrino, Steicy, Six, Emmanuelle, Gobeaux, Camille, Auberger, Patrick, Hérault, Olivier, Pflumio, Françoise, Arcangeli, Marie-Laure
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10552687/
https://www.ncbi.nlm.nih.gov/pubmed/37616262
http://dx.doi.org/10.1093/stcltm/szad049
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author Henry, Elia
Picou, Frédéric
Barroca, Vilma
Dechamps, Nathalie
Sobrino, Steicy
Six, Emmanuelle
Gobeaux, Camille
Auberger, Patrick
Hérault, Olivier
Pflumio, Françoise
Arcangeli, Marie-Laure
author_facet Henry, Elia
Picou, Frédéric
Barroca, Vilma
Dechamps, Nathalie
Sobrino, Steicy
Six, Emmanuelle
Gobeaux, Camille
Auberger, Patrick
Hérault, Olivier
Pflumio, Françoise
Arcangeli, Marie-Laure
author_sort Henry, Elia
collection PubMed
description In a steady state, hematopoietic stem cells (HSC) exhibit very low levels of reactive oxygen species (ROS). Upon stress, HSC get activated and enter into proliferation and differentiation process to ensure blood cell regeneration. Once activated, their levels of ROS increase, as messengers to mediate their proliferation and differentiation programs. However, at the end of the stress episode, ROS levels need to return to normal to avoid HSC exhaustion. It was shown that antioxidants can prevent loss of HSC self-renewal potential in several contexts such as aging or after exposure to low doses of irradiation suggesting that antioxidants can be used to maintain HSC functional properties upon culture-induced stress. Indeed, in humans, HSC are increasingly used for cell and gene therapy approaches, requiring them to be cultured for several days. As expected, we show that a short culture period leads to drastic defects in HSC functional properties. Moreover, a switch of HSC transcriptional program from stemness to differentiation was evidenced in cultured HSC. Interestingly, cultured-HSC treated with 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl (4-hydroxy-TEMPO or Tempol) exhibited a higher clonogenic potential in secondary colony forming unit cell (CFU-C) assay and higher reconstitution potential in xenograft model, compared to untreated cultured-HSC. By transcriptomic analyses combined with serial CFU-C assays, we show that Tempol, which mimics superoxide dismutase, protects HSC from culture-induced stress partly through VEGFα signaling. Thus, we demonstrate that adding Tempol leads to the protection of HSC functional properties during ex vivo culture.
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spelling pubmed-105526872023-10-06 The Antioxidant TEMPOL Protects Human Hematopoietic Stem Cells From Culture-Mediated Loss of Functions Henry, Elia Picou, Frédéric Barroca, Vilma Dechamps, Nathalie Sobrino, Steicy Six, Emmanuelle Gobeaux, Camille Auberger, Patrick Hérault, Olivier Pflumio, Françoise Arcangeli, Marie-Laure Stem Cells Transl Med Cord Blood In a steady state, hematopoietic stem cells (HSC) exhibit very low levels of reactive oxygen species (ROS). Upon stress, HSC get activated and enter into proliferation and differentiation process to ensure blood cell regeneration. Once activated, their levels of ROS increase, as messengers to mediate their proliferation and differentiation programs. However, at the end of the stress episode, ROS levels need to return to normal to avoid HSC exhaustion. It was shown that antioxidants can prevent loss of HSC self-renewal potential in several contexts such as aging or after exposure to low doses of irradiation suggesting that antioxidants can be used to maintain HSC functional properties upon culture-induced stress. Indeed, in humans, HSC are increasingly used for cell and gene therapy approaches, requiring them to be cultured for several days. As expected, we show that a short culture period leads to drastic defects in HSC functional properties. Moreover, a switch of HSC transcriptional program from stemness to differentiation was evidenced in cultured HSC. Interestingly, cultured-HSC treated with 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl (4-hydroxy-TEMPO or Tempol) exhibited a higher clonogenic potential in secondary colony forming unit cell (CFU-C) assay and higher reconstitution potential in xenograft model, compared to untreated cultured-HSC. By transcriptomic analyses combined with serial CFU-C assays, we show that Tempol, which mimics superoxide dismutase, protects HSC from culture-induced stress partly through VEGFα signaling. Thus, we demonstrate that adding Tempol leads to the protection of HSC functional properties during ex vivo culture. Oxford University Press 2023-08-24 /pmc/articles/PMC10552687/ /pubmed/37616262 http://dx.doi.org/10.1093/stcltm/szad049 Text en © The Author(s) 2023. Published by Oxford University Press. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com.
spellingShingle Cord Blood
Henry, Elia
Picou, Frédéric
Barroca, Vilma
Dechamps, Nathalie
Sobrino, Steicy
Six, Emmanuelle
Gobeaux, Camille
Auberger, Patrick
Hérault, Olivier
Pflumio, Françoise
Arcangeli, Marie-Laure
The Antioxidant TEMPOL Protects Human Hematopoietic Stem Cells From Culture-Mediated Loss of Functions
title The Antioxidant TEMPOL Protects Human Hematopoietic Stem Cells From Culture-Mediated Loss of Functions
title_full The Antioxidant TEMPOL Protects Human Hematopoietic Stem Cells From Culture-Mediated Loss of Functions
title_fullStr The Antioxidant TEMPOL Protects Human Hematopoietic Stem Cells From Culture-Mediated Loss of Functions
title_full_unstemmed The Antioxidant TEMPOL Protects Human Hematopoietic Stem Cells From Culture-Mediated Loss of Functions
title_short The Antioxidant TEMPOL Protects Human Hematopoietic Stem Cells From Culture-Mediated Loss of Functions
title_sort antioxidant tempol protects human hematopoietic stem cells from culture-mediated loss of functions
topic Cord Blood
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10552687/
https://www.ncbi.nlm.nih.gov/pubmed/37616262
http://dx.doi.org/10.1093/stcltm/szad049
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