Eltrombopag increases the hematopoietic supporting ability of mesenchymal stem/stromal cells
[EN]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 ef...
| Autores: | , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2022 |
| País: | España |
| Institución: | Universidad de Salamanca (USAL) |
| Repositorio: | GREDOS. Repositorio Institucional de la Universidad de Salamanca |
| OAI Identifier: | oai:gredos.usal.es:10366/161402 |
| Acceso en línea: | http://hdl.handle.net/10366/161402 |
| Access Level: | acceso abierto |
| Palabra clave: | Aplasia, Eltrombopag, Hematopoiesis, Mesenchymal stem cells, MSC Aplasia Eltrombopag Hematopoiesis Mesenchymal stem cells Receptors, Thrombopoietin Anemia, Aplastic Mesenchymal Stromal Cells 3205.04 Hematología hematopoyesis receptores de trombopoyetina células del estroma mesenquimatoso anemia aplásica |
| Sumario: | [EN]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. genomewide 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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