Natural estrogens enhance the engraftment of human hematopoietic stem and progenitor cells in immunodeficient mice
Sara Fañanas-BaqueroIsrael OrmanFederico Becerra-AparicioS. B. MiguelJordi Garcia MerinoRosa María Pérez YáñezYolanda Fernandez SainzRebeca Sánchez‐DomínguezMercedes Dessy-RodríguezOmaira AlberquillaDavid AlfaroA. ZapataJuan A. BuerenJosé C. SegoviaOscar Quintana‐Bustamante
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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 after myeloablative conditioning, especially when limiting numbers of Hematopoietic Stem and Progenitor Cells are available.Keywords:
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Bone marrow-derived circulating endothelial progenitor cells have been succesfully used to enhance angiogenesis after tissue ischemia. The role of endothelial progenitor cells in endothelial cell homeostasis and their putative role in atherogenesis have been recently investigated. Cardiovascular risk factors negatively influence endothelial progenitor cell number and function while vasculoprotection e.g. by statins, estrogens and physical activity may be partly mediated by progenitor cells. Endogenous mobilization or injection of ex-vivo generated endothelial progenitor cells is associated with an enhanced reendothelialization, an improvement of endothelial function and reduced athersclerotic burden. In contrast, endothelial progenitor cells may promote plaque angiogenesis in animal models and may negatively influence plaque development and stability. However, in humans with coronary atherosclerotic disease, endothelial progenitor cells are a novel risk prdictor for cardiovascular mortality and morbidity. In this review we focus on the role of circulating endothelial progenitor cells in endothelial cell repair mechanisms at the vascular wall and their potentially protective and therapeutic role in atherosclerotic disease.
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After the injury of vascular endothelial,bone marrow-derived endothelial progenitor cell can be mobilized into the peripheral circulation,home to ischemic areas or sites of vascular damage,inducing endothelial cell proliferation,migration or differentiating into functional mature endothelial cell to promote the reendothelization of the damaged vessels.So it may become a new tool for treatment of cardiovascular disease.However,the signaling pathway that regulates endothelial progenitor cell proliferation,migration,differentiation and other biological characteristics needs to be thoroughly researched,which is not only difficult,but also hot in this area.This review will focus on the research regulation of endothelial progenitor cell signaling pathway.
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Integrity of vascular endothelial structure and function keeps the cardiovascular system in steady state. Endothelial dysfunction and limited repair ability is thought to result in the development of many vascular diseases. Endothelial progenitor cells are precursors of vascular endothelial cell,which play an important role in maintaining endothelial steady state and promote the vascular repair. In recent years the researchers of endothelial progenitor cells found they are closely related to hypertension disease occurrence and development. The decrease in the number and function disorder could lead to an increased risk for hypertension disease. Hypertension is a damage to endothelial progenitor cells as an independent risk factor. Here is to make a review of the research progress of relationship between endothelia progenitor cell and hypertension.
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Accumulating evidence indicates the impact of endothelial progenitor cells (EPCs) in vascular repair. In patients, the number of EPCs is negatively correlated with the severity of atherosclerosis. In various animal models, transplantation of bone marrow-derived progenitor cells could sufficiently rescue organ function and enhance vascular repair and tissue regeneration. Increase in the number of circulating progenitors, induced by cell transfusion or enhanced mobilization, can also enhance restoration and integrity of the endothelial lining, suppress neointimal formation, and increase blood flow to ischaemic sites. However, the beneficial outcome of EPC infusion very much depends on the growth and differentiation factors within the tissue, cell-to-cell interactions, and the degree of injury. As highlighted by several studies, EPCs derive from different sources including bone marrow and non-bone marrow organs such as the spleen, the functional repair properties of which may vary with the maturation state of the cell. Thus, understanding the molecular mechanisms involved in EPC-repairing processes is essential. In the present review we focus on the role of EPCs in vascular diseases, and we provide an update on the mechanisms of EPC mobilization, homing, and differentiation.
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Cardiovascular disease is associated with damage of the endothelial monolayer leading to endothelial dysfunction and atherosclerosis. A growing body of evidence suggests that circulating endothelial progenitor cells play an important role in endothelial cell regeneration. In this review we discuss the evolving role of stem- and progenitor cells in the maintenance of the vascular wall focusing on new pathophysiological concepts of endothelial cell regeneration. We discuss new insights into vascular stem cell biology derived from experimental and clinical studies.
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Endothelial progenitor cells(EPCs) are precursors of endothelial cells,which are able to differentiate into mature endothelial cells.Studies are needed to increase more detailed understanding on the mechanisms of EPCs differentiation,survival,homing and distribution of the tissue.The human EPCs has potential to be used as diagnostic and prognostic or therapeutic tools in the future.This paper reviewed the biological characteristics and its advancement of EPCs,which including separation,culture and iden-tification,surface marker,mobilization,differentiation and homing.
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The first description of endothelial progenitor cells in 1997 rapidly lead to substantial changes in our understanding of angiogenesis.In the subsequent 10 years researchers have investigated methods of inducing,isolating and culturing endothelial progenitor cells,as well as identification and differentiation,resulting in endothelial progenitor cells emerging as a promising candidate for treating ischemic heart disease.Studies have shown that the introduction of endothelial progenitor cells can restore tissue vascularization,as well as target tumor growth.This review examines the general features and functions of endothelial progenitor cells currently being investigated,and includes some perspectives on the future of endothelial progenitor cell therapy.
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