Cytokine-induced hematopoietic stem and progenitor cell mobilization: unraveling interactions between stem cells and their niche

Peripheral blood hematopoietic stem and progenitor cells (HSPCs), mobilized by granulocyte colony-stimulating factor, are widely used as a source for both autologous and allogeneic stem cell transplantation. The use of mobilized HSPCs has several advantages over traditional bone marrow-derived HSPCs, including a less invasive harvesting process for the donor, higher HSPC yields, and faster hematopoietic reconstitution in the recipient. For years, the mechanisms by which cytokines and other agents mobilize HSPCs from the bone marrow were not fully understood. The field of stem cell mobilization research has advanced significantly over the past decade, with major breakthroughs in the elucidation of the complex mechanisms that underlie stem cell mobilization. In this review, we provide an overview of the events that underlie HSPC mobilization and address the relevant cellular and molecular components of the bone marrow niche. Furthermore, current and future mobilizing agents will be discussed

Biology of cytokine-induced hematopoietic stem and progenitor cell mobilization

Hematopoietic stem and progenitor cells (HSPC) reside in specific niches in the bone marrow, where they are part of a complex micro-environment. Several cytokines, chemokines and small molecules are involved in mobilization of HSPC from the bone marrow towards peripheral blood. This thesis describes several studies on the mechanisms of HSPC mobilization: the kinetics of HSPC mobilization following the administration of Flt3-ligand in a murine model, the effects of repeated in vivo administration of recombinant human G-CSF and murine recombinant G-CSF in mice, the role of alpha-1-antitrypsin in steady state and during G-CSF-induced mobilization in humans and the effects of mesenchymal stromal cells on the stem cell niche in a murine model of G-CSF-induced HSPC mobilization.LUMC / Geneeskund

Yellow swelling around the eyes: periocular lymphoma

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Mesenchymal stromal cells induce a permissive state in the bone marrow that enhances G-CSF-induced hematopoietic stem cell mobilization in mice

Transplantation and autoimmunit

Mesenchymal Stromal Cells Enhance G-CSF-Induced Mobilization Of Hematopoietic Stem- and Progenitor Cells

Stemcel biology/Regenerative medicine (incl. bloodtransfusion

Enhancement of G-CSF-induced stem cell mobilization by antibodies against the beta2 integrins LFA-1 and Mac-1

Item does not contain fulltextThe beta 2 integrins leukocyte function antigen-1 (LFA-1, CD11a) and macrophage antigen-1 (Mac-1, CD11b) have been reported to play a role in the attachment of CD34(+) cells to stromal cells in the bone marrow. When administered prior to interleukin-8 (IL-8), anti-LFA-1 antibodies completely prevent the IL-8-induced mobilization of hematopoietic stem cells in mice. Here, we studied the role of anti-beta 2 integrin antibodies in granulocyte colony-stimulating factor (G-CSF)-induced mobilization of hematopoietic progenitor cells. Administration of antibodies against the alpha chain of LFA-1 or against the alpha chain of Mac-1 followed by daily injections of G-CSF for more than 1 day resulted in a significant enhancement of mobilization of hematopoietic progenitor cells when compared with mobilization induced by G-CSF alone. Also, the number of late (day 28) cobblestone area-forming cells in vitro was significantly higher after mobilization with anti-LFA-1 antibodies followed by 5 microg G-CSF for 5 days than with G-CSF alone (119 +/- 34 days vs 17 +/- 14 days), indicating mobilization of repopulating stem cells. Pretreatment with blocking antibodies to intercellular adhesion molecule-1 (ICAM-1; CD54), a ligand of LFA-1 and Mac-1, did not result in an effect on G-CSF-induced mobilization, suggesting that the enhancing effect required an interaction of the beta 2 integrins and one of their other ligands. Enhancement of mobilization was not observed in LFA-1-deficient (CD11a) mice, indicating that activated cells expressing LFA-1 mediate the synergistic effect, rather than LFA-1-mediated adhesion

Phase 1/2 Trial Of Lenalidomide In Combination With Cyclophosphamide and Prednisone (REP) In Patients With Lenalidomide-Refractory Multiple Myeloma (REPEAT-study)

Stemcel biology/Regenerative medicine (incl. bloodtransfusion