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Natural estrogens enhance the engraftment of human hematopoietic stem and progenitor cells in immunodeficient mice

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Fañanas-Baquero, Sara and Orman, Israel and Becerra Aparicio, Federico and Bermudez de Miguel, Silvia and Garcia Merino, Jordi and Yañez, Rosa and Fernández Sainz, Yolanda and Sánchez, Rebeca and Dessy-Rodríguez, Mercedes and Alberquilla, Omaira and Alfaro Sánchez, David and Zapata González, Agustín and Bueren, Juan A. and Segovia, Jose Carlos and Quintana-Bustamante, Oscar (2020) Natural estrogens enhance the engraftment of human hematopoietic stem and progenitor cells in immunodeficient mice. Haematologica, 105 . pp. 1-60. ISSN 0390-6078, ESSN: 1592-8721

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Official URL: http://www.haematologica.org/content/early/2020/04/29/haematol.2019.233924.full.pdf+html



Abstract

Hematopoietic Stem and Progenitor Cells are crucial in the maintenance of lifelong production of all blood cells. These Stem Cells are highly regulated to maintain homeostasis through a delicate balance between quiescence, self-renewal and differentiation. However, this balance is altered during the hematopoietic recovery after Hematopoietic Stem and Progenitor Cell Transplantation. Transplantation efficacy can be limited by inadequate Hematopoietic Stem Cells number, poor homing, low level of engraftment, or limited self-renewal. As recent evidences indicate that estrogens are involved in regulating the hematopoiesis, we sought to examine whether natural estrogens (estrone or E1, estradiol or E2, estriol or E3 and estetrol or E4) modulate human Hematopoietic Stem and Progenitor Cells. Our results show that human Hematopoietic Stem and Progenitor Cell subsets express estrogen receptors, and whose signaling is activated by E2 and E4 on these cells. Additionally, these natural estrogens cause different effects on human Progenitors in vitro. We found that both E2 and E4 expand human Hematopoietic Stem and Progenitor Cells. However, E4 was the best tolerated estrogen and promoted cell cycle of human Hematopoietic Progenitors. Furthermore, we identified that E2 and, more significantly, E4 doubled human hematopoietic engraftment in immunodeficient mice without altering other Hematopoietic Stem and Progenitor Cells properties. Finally, the impact of E4 on promoting human hematopoietic engraftment in immunodeficient mice might be mediated through the regulation of mesenchymal stromal cells in the bone marrow niche. Together, our data demonstrate that E4 is well tolerated and enhances human reconstitution in immunodeficient mice, directly by modulating human Hematopoietic Progenitor properties and indirectly by interacting with the bone marrow niche. This application might have particular relevance to ameliorate the hematopoietic recovery 3 after myeloablative conditioning, especially when limiting numbers of Hematopoietic Stem and Progenitor Cells are available.


Item Type:Article
Uncontrolled Keywords:Hematopoietic stem cell; Hematopoiesis; Stem cell transplantation
Subjects:Medical sciences > Medicine > Hematology
Medical sciences > Biology > Cytology
ID Code:61310
Deposited On:02 Jul 2020 08:56
Last Modified:02 Jul 2020 08:56

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