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

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dc.contributor.authorFañanas-Baquero, Sara
dc.contributor.authorOrman, Israel
dc.contributor.authorBecerra Aparicio, Federico
dc.contributor.authorBermudez de Miguel, Silvia
dc.contributor.authorGarcia Merino, Jordi
dc.contributor.authorYañez, Rosa
dc.contributor.authorFernández Sainz, Yolanda
dc.contributor.authorSánchez, Rebeca
dc.contributor.authorDessy-Rodríguez, Mercedes
dc.contributor.authorAlberquilla, Omaira
dc.contributor.authorAlfaro Sánchez, David
dc.contributor.authorZapata González, Agustín
dc.contributor.authorBueren, Juan A.
dc.contributor.authorSegovia, Jose Carlos
dc.contributor.authorQuintana-Bustamante, Oscar
dc.date.accessioned2023-06-16T15:19:35Z
dc.date.available2023-06-16T15:19:35Z
dc.date.issued2020-04
dc.description.abstractHematopoietic 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.
dc.description.departmentDepto. de Biología Celular
dc.description.facultyFac. de Ciencias Biológicas
dc.description.refereedTRUE
dc.description.sponsorshipMinisterio de Economía y Competitividad (MINECO /Fondo Europeo de Desarrollo Regional (FEDER)
dc.description.sponsorshipInstituto de Salud Carlos III (ISCIII).Fondo de Investigaciones Sanitarias
dc.description.sponsorshipComunidad de Madrid
dc.description.statuspub
dc.eprint.idhttps://eprints.ucm.es/id/eprint/61310
dc.identifier.doi10.3324/haematol.2019.233924
dc.identifier.issn0390-6078, ESSN: 1592-8721
dc.identifier.officialurlhttp://www.haematologica.org/content/early/2020/04/29/haematol.2019.233924.full.pdf+html
dc.identifier.urihttps://hdl.handle.net/20.500.14352/6358
dc.journal.titleHaematologica
dc.language.isoeng
dc.page.final60
dc.page.initial1
dc.publisherFerrata Storti Foundation
dc.relation.projectID(SAF2017-84248-P)
dc.relation.projectID(RD16/0011/0011)
dc.rightsAtribución-NoComercial 3.0 España
dc.rights.accessRightsopen access
dc.rights.urihttps://creativecommons.org/licenses/by-nc/3.0/es/
dc.subject.cdu612.119
dc.subject.cdu611.018.5
dc.subject.cdu577.175.6
dc.subject.keywordHematopoietic stem cell
dc.subject.keywordHematopoiesis
dc.subject.keywordStem cell transplantation
dc.subject.ucmHematología
dc.subject.ucmBiología celular (Biología)
dc.subject.unesco3205.04 Hematología
dc.subject.unesco2407 Biología Celular
dc.titleNatural estrogens enhance the engraftment of human hematopoietic stem and progenitor cells in immunodeficient mice
dc.typejournal article
dc.volume.number105
dspace.entity.typePublication
relation.isAuthorOfPublication58e4dddb-810a-4cc1-9bbe-083be83d06fd
relation.isAuthorOfPublication.latestForDiscovery58e4dddb-810a-4cc1-9bbe-083be83d06fd
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