RT Journal Article
T1 Natural estrogens enhance the engraftment of human hematopoietic stem and progenitor cells in immunodeficient mice
A1 Fañanas-Baquero, Sara
A1 Orman, Israel
A1 Becerra Aparicio, Federico
A1 Bermudez de Miguel, Silvia
A1 Garcia Merino, Jordi
A1 Yañez, Rosa
A1 Fernández Sainz, Yolanda
A1 Sánchez, Rebeca
A1 Dessy-Rodríguez, Mercedes
A1 Alberquilla, Omaira
A1 Alfaro Sánchez, David
A1 Zapata González, Agustín
A1 Bueren, Juan A.
A1 Segovia, Jose Carlos
A1 Quintana-Bustamante, Oscar
AB 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.
PB Ferrata Storti Foundation
SN 0390-6078, ESSN: 1592-8721
YR 2020
FD 2020-04
LK https://hdl.handle.net/20.500.14352/6358
UL https://hdl.handle.net/20.500.14352/6358
LA eng
NO Ministerio de Economía y Competitividad (MINECO /Fondo Europeo de Desarrollo Regional (FEDER)
NO Instituto de Salud Carlos III (ISCIII).Fondo de Investigaciones Sanitarias
NO Comunidad de Madrid
DS Docta Complutense
RD 29 abr 2024