Mobilization of hematopoietic stem cells from the bone marrow niche to the blood compartment

The vast majority of hematopoietic stem cells (HSCs) reside in specialized niches within the bone marrow during steady state, maintaining lifelong blood cell production. A small number of HSCs normally traffic throughout the body; however, exogenous stimuli can enhance their release from the niche and entry into the peripheral circulation. This process, termed mobilization, has become the primary means to acquire a stem cell graft for hematopoietic transplant at most transplant centers. Currently, the preferred method of HSC mobilization for subsequent transplantation is treatment of the donor with granulocyte colony-stimulating factor. The mobilizing effect of granulocyte colony-stimulating factor is not completely understood, but recent studies suggest that its capacity to mobilize HSCs, at least in part, is a consequence of alterations to the hematopoietic niche. The present article reviews some of the key mechanisms mediating HSC mobilization, highlighting recent advances and controversies in the field

IFN-1 Bid crosstalk: foe or friend to stem cells

Comment on DNA Damage-Induced HSPC Malfunction Depends on ROS Accumulation Downstream of IFN-1 Signaling and Bid Mobilization. [Cell Stem Cell. 2016

Inhibition of DPP4/CD26 and dmPGE2 treatment enhances engraftment of mouse bone marrow hematopoietic stem cells

Enhancing the engraftment of hematopoietic stem cells (HSC) is especially important when times to engraftment are prolonged due either to limiting numbers of HSC in the donor graft or to intrinsic slower engrafting time of the tissue sources of HSC. Both inhibition of Dipeptidylpeptidase (DPP) 4/CD26 and treatment of cells with 16,16 dimethyl prostaglandin E2 (dmPGE2) have been shown to enhance hematopoietic stem cell engraftment in murine transplantation models and have been evaluated in clinical settings for their influence on engraftment of cord blood cells, a tissue source of HSC known to manifest an extended time to engraftment of donor cells compared to that of bone marrow (BM) and mobilized peripheral blood for hematopoietic cell transplantation (HCT). Herein, we present new experimental data, using a CD45+ head-to head congenic model of donor mouse BM cells for engraftment of lethally-irradiated mice, demonstrating that similar levels of enhanced engraftment are detected by pulsing donor BM cells with Diprotin A, a DPP4 inhibitor, or with dmPGE2 prior to infusion, or by pretreating recipient mice with sitagliptin, also a DPP4 inhibitor, by oral gavage. Moreover, the combined effects of pretreating the donor BM cells with dmPGE2 in context of pretreating the recipient mice with sitagliptin after administration of a lethal dose of radiation resulted in significantly enhanced competitively repopulating HCT compared to either treatment alone. This information is highly relevant to the goal of enhancing engraftment in human clinical HCT

Peripheral Blood Stem Cell Mobilization: a Look Ahead

The purpose of review: Mobilized peripheral blood is the predominant source of stem and progenitor cells for hematologic transplantation. Successful transplant requires sufficient stem cells of high enough quality to recapitulate lifelong hematopoiesis, but in some patients and normal donors, reaching critical threshold stem cell numbers are difficult to achieve. Novel strategies, particularly those offering rapid mobilization and reduced costs, remains an area of interest. This review summarizes critical scientific underpinnings in understanding the process of stem cell mobilization, with a focus on new or improved strategies for their efficient collection and engraftment. Recent findings: Studies are described that provide new insights into the complexity of stem cell mobilization. Agents that target new pathways such HSC egress, identify strategies to collect more potent competing HSC and new methods to optimize stem cell collection and engraftment are being evaluated. Summary: Agents and more effective strategies that directly address the current shortcomings of hematopoietic stem cell mobilization and transplantation and offer the potential to facilitate collection and expand use of mobilized stem cells have been identified

Pulse exposure of haematopoietic grafts to prostaglandin E2 in vitro facilitates engraftment and recovery

OBJECTIVES: The aim of this study was to evaluate the effects of prostaglandin E(2) (PGE(2) ) on haematopoietic stem cell (HSC) function and determine its mechanism of action. MATERIALS AND METHODS: HSC were exposed to PGE(2) for 2 h and effects on their homing, engraftment and self-renewal evaluated in vivo. Effects of PGE(2) on HSC cell cycle, CXCR4 expression and migration to SDF-1α were analysed in vitro. Apoptosis was evaluated by examination of survivin expression and active caspase-3 levels. RESULTS: Equivalent haematopoietic reconstitution was demonstrated using 4-fold fewer PGE(2) -treated cells compared to controls. Multilineage reconstitution was stable on secondary transplantation, indicating that PGE(2) affects long-term repopulating HSC (LT-HSC) and that enhanced chimaerism of PGE(2) -pulsed cells results from their initial treatment. PGE(2) increased CXCR4 expression on mouse and human HSC, increased their migration to SDF-1αin vitro and enhanced in vivo marrow homing 2-fold, which was blocked by a CXCR4 receptor antagonist. PGE(2) pulse exposure reduced apoptosis of mouse and human HSC, with increase in endogenous caspase inhibitor survivin, and concomitant decrease in active caspase-3. Two-fold more HSC entered the cell cycle and proliferated within 24 h after PGE(2) pulse exposure. CONCLUSIONS: These studies demonstrate that short-term PGE(2) exposure enhances HSC function and supports the concept of utility of PGE(2) as an ex vivo strategy to improve function of haematopoietic grafts, particularly those where HSC numbers are limited

Cosmopolitisme et internationalisme : théories, pratiques, combats (XVe - XXIe siècles)

National audienceLes contributions rassemblées dans ce volume se proposent d’illustrer ce double niveau : que signifie « être citoyen du monde », aujourd’hui, etautrefois ? Qui sont ces « citoyens du monde » aux différentes étapes de l’Histoire ? Les « cosmopolites » ne sont ils qu’une petite élite, intellectuelle ou sociale, peu en prise sur les réalités massives de leur temps ? Leur philosophie n’est-elle qu’un idéalisme aveugle, une simple utopie, ou bien au contraire voit-elle loin, assez loin pour inspirer encore de nos jours un vrai cosmopolitisme, c’est-à-dire une volonté agissante à l’échelle de l’humanité ? Quels liens peut-on établir dans l’Histoire entre cosmopolitisme et internationalisme, ce dernier terme impliquant, même si c’est pour la critiquer, l’idée de « nation » comme point de départ d’une coopération entre les peuples ? Cette introduction se contentera, à partir des textes réunis dans ce volume, signés par des spécialistes de divers champs du savoir, d’ouvrir quelques pistes à la méditation

Sowing the Seeds of a Fruitful Harvest: Hematopoietic Stem Cell Mobilization

Hematopoietic stem cell transplantation is the only curative option for a number of malignant and non-malignant diseases. As the use of hematopoietic transplant has expanded, so too has the source of stem and progenitor cells. The predominate source of stem and progenitors today, particularly in settings of autologous transplantation, is mobilized peripheral blood. This review will highlight the historical advances which lead to the widespread use of peripheral blood stem cells for transplantation, with a look towards future enhancements to mobilization strategies