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Eltrombopag increases the hematopoietic supporting ability of mesenchymal stem/stromal cells

BACKGROUND: Eltrombopag (EP) is a small molecule that acts directly on hematopoietic stem cells (HSCs) and megakaryocytes to stimulate the hematopoietic process. Mesenchymal stem/stromal cells (MSCs) are key hematopoietic niche regulators. OBJECTIVES: We aimed to determine whether EP has any effect...

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Autores principales: Muntión, Sandra, Preciado, Silvia, Sánchez-Luis, Elena, Corchete, Luis, Díez-Campelo, María, Osugui, Lika, Martí-Chillón, Gerardo-Javier, Vidriales, María-Belén, Navarro-Bailón, Almudena, De Las Rivas, Javier, Sánchez-Guijo, Fermín
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9806379/
https://www.ncbi.nlm.nih.gov/pubmed/36601635
http://dx.doi.org/10.1177/20406207221142137
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author Muntión, Sandra
Preciado, Silvia
Sánchez-Luis, Elena
Corchete, Luis
Díez-Campelo, María
Osugui, Lika
Martí-Chillón, Gerardo-Javier
Vidriales, María-Belén
Navarro-Bailón, Almudena
De Las Rivas, Javier
Sánchez-Guijo, Fermín
author_facet Muntión, Sandra
Preciado, Silvia
Sánchez-Luis, Elena
Corchete, Luis
Díez-Campelo, María
Osugui, Lika
Martí-Chillón, Gerardo-Javier
Vidriales, María-Belén
Navarro-Bailón, Almudena
De Las Rivas, Javier
Sánchez-Guijo, Fermín
author_sort Muntión, Sandra
collection PubMed
description BACKGROUND: Eltrombopag (EP) is a small molecule that acts directly on hematopoietic stem cells (HSCs) and megakaryocytes to stimulate the hematopoietic process. Mesenchymal stem/stromal cells (MSCs) are key hematopoietic niche regulators. OBJECTIVES: We aimed to determine whether EP has any effect on MSC function and properties (especially on their hematopoietic-supporting ability) and if so, what changes (e.g. genome-wide transcriptomic alterations) are induced in MSC after EP treatment. DESIGN/METHODS: MSCs were isolated from 12 healthy donors and treated with 15 µM and 50 µM of EP for 24 h. The toxicity of the drug on MSCs and their differentiation ability were analyzed, as well as the transcriptomic profile, reactive oxygen species (ROS) and DNA damage and the changes induced in the clonogenic capacity of HSCs. RESULTS: The results show that EP also modifies MSC functions, decreasing their adipogenic differentiation, increasing the expression of genes involved in hypoxia and other pathways related to oxygen homeostasis, and enhancing their ability to support hematopoiesis in vitro. CONCLUSION: Our findings support the use of EP in cases where hematopoiesis is defective, despite its well-known direct effects on hematopoietic cells. Our findings suggest that further studies on the effects of EP on MSCs from patients with aplastic anemia are warranted.
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spelling pubmed-98063792023-01-03 Eltrombopag increases the hematopoietic supporting ability of mesenchymal stem/stromal cells Muntión, Sandra Preciado, Silvia Sánchez-Luis, Elena Corchete, Luis Díez-Campelo, María Osugui, Lika Martí-Chillón, Gerardo-Javier Vidriales, María-Belén Navarro-Bailón, Almudena De Las Rivas, Javier Sánchez-Guijo, Fermín Ther Adv Hematol Original Research BACKGROUND: Eltrombopag (EP) is a small molecule that acts directly on hematopoietic stem cells (HSCs) and megakaryocytes to stimulate the hematopoietic process. Mesenchymal stem/stromal cells (MSCs) are key hematopoietic niche regulators. OBJECTIVES: We aimed to determine whether EP has any effect on MSC function and properties (especially on their hematopoietic-supporting ability) and if so, what changes (e.g. genome-wide transcriptomic alterations) are induced in MSC after EP treatment. DESIGN/METHODS: MSCs were isolated from 12 healthy donors and treated with 15 µM and 50 µM of EP for 24 h. The toxicity of the drug on MSCs and their differentiation ability were analyzed, as well as the transcriptomic profile, reactive oxygen species (ROS) and DNA damage and the changes induced in the clonogenic capacity of HSCs. RESULTS: The results show that EP also modifies MSC functions, decreasing their adipogenic differentiation, increasing the expression of genes involved in hypoxia and other pathways related to oxygen homeostasis, and enhancing their ability to support hematopoiesis in vitro. CONCLUSION: Our findings support the use of EP in cases where hematopoiesis is defective, despite its well-known direct effects on hematopoietic cells. Our findings suggest that further studies on the effects of EP on MSCs from patients with aplastic anemia are warranted. SAGE Publications 2022-12-26 /pmc/articles/PMC9806379/ /pubmed/36601635 http://dx.doi.org/10.1177/20406207221142137 Text en © The Author(s), 2022 https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Original Research
Muntión, Sandra
Preciado, Silvia
Sánchez-Luis, Elena
Corchete, Luis
Díez-Campelo, María
Osugui, Lika
Martí-Chillón, Gerardo-Javier
Vidriales, María-Belén
Navarro-Bailón, Almudena
De Las Rivas, Javier
Sánchez-Guijo, Fermín
Eltrombopag increases the hematopoietic supporting ability of mesenchymal stem/stromal cells
title Eltrombopag increases the hematopoietic supporting ability of mesenchymal stem/stromal cells
title_full Eltrombopag increases the hematopoietic supporting ability of mesenchymal stem/stromal cells
title_fullStr Eltrombopag increases the hematopoietic supporting ability of mesenchymal stem/stromal cells
title_full_unstemmed Eltrombopag increases the hematopoietic supporting ability of mesenchymal stem/stromal cells
title_short Eltrombopag increases the hematopoietic supporting ability of mesenchymal stem/stromal cells
title_sort eltrombopag increases the hematopoietic supporting ability of mesenchymal stem/stromal cells
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9806379/
https://www.ncbi.nlm.nih.gov/pubmed/36601635
http://dx.doi.org/10.1177/20406207221142137
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