Defining the pathways of early adult hematopoiesis

The journeys that hematopoietic cells take to differentiate from long-term stem cells into committed cells have recently been a topic of debate. In this issue of Cell Stem Cell, Arinobu et al. (2007) and Pronk et al. (2007) provide new insights into the paths traveled by hematopoietic progenitors.     

An SDF-1 trap for myeloid cells stimulates angiogenesis

In this issue of Cell, Grunewald et al. (2005) examine the role of hematopoietic cells in the formation of new blood vessels. They show that organ-specific expression of vascular endothelial growth factor (VEGF) is sufficient to mobilize and recruit hematopoietic cells from the bone marrow to the blood, but retention of the proangiogenic subpopulation of hematopoietic cells in peripheral organs requires an additional factor, stromal-derived factor 1 (SDF-1).     

Contribution of the fibrinolytic pathway to hematopoietic regeneration

Hematopoietic stem cells (HSCs) can differentiate and proliferate in response to hematopoietic stress (e.g., myelosuppression, infections, and allergic reactions), thereby ensuring a well‐regulated supply of mature and immature hematopoietic cells within the circulation and prompt adjustment of blood cell levels within normal ranges. The recovery of tissues and organs from hematopoietic stress (e.g., myelosuppression or ionizing irradiation) is dependent on two cell types: resident HSCs which repopulate the bone marrow (BM) cavity, and stromal cells. BM regeneration critically depends on the release of soluble factors from cells such as stromal cells, a process regulated by proteases. Two proteolytic systems, the fibrinolytic system and the matrix metalloproteinases (MMPs), have recently been shown to be involved in this process (Heissig B, 2007, Cell Stem Cell 1: 658–670). The plasminogen/plasmin system is mostly recognized for its fibrinolytic activity, but it is also involved in processes such as cell invasion, chemotaxis, growth factor activity modulation, and tissue remodeling. This review focuses on the role of plasmin and its activators as key players in controlling the hematopoietic stress response after myelosuppression (hematopoietic regeneration). Aspects of plasmin regulation, especially regulation of its ability to activate MMPs and the functional consequences of this enzyme activation, such as plasmin‐mediated release of biologically relevant cytokines from the matrix and cell surfaces, will be discussed. J. Cell. Physiol. 221: 521–525, 2009. © 2009 Wiley‐Liss, Inc.     

Wnt signaling in the niche

There is much interest in understanding the signals in the bone marrow niche that keep hematopoietic stem cells (HSCs) in a quiescent state. In the current issue of Cell Stem Cell, Fleming et al. (2008) report that blocking Wnt signaling in the niche increases the number of proliferating HSCs and reduces their ability to reconstitute the hematopoietic system of irradiated recipient mice. These findings show that Wnt/beta-catenin activity is crucial for the maintenance of HSC quiescence in the bone marrow niche.     

Stem cells remember their grade

The stem cell state is understood based on what cells do in performance assays, crude measures of a highly refined state. In this issue of Cell Stem Cell, Dykstra et al. (2007) reveal stem cell gradation and the extent to which that gradation is retained in stem cell daughters of hematopoietic stem cells.     

A roundabout way to the niche

A new player in hematopoietic stem cell (HSC)-niche interactions is introduced in this issue of Cell Stem Cell. Smith-Berdan et al. (2010) demonstrate that Robo4 is involved in HSC engraftment and mobilization and does so in cooperation with Cxcr4 to guide stem cells to and secure them in the niche.     

Does N-Cadherin Regulate Interaction of Hematopoietic Stem Cells with Their Niches?

In this issue of Cell Stem Cell, Kiel et al. (2007) demonstrate that N-cadherin is not expressed on repopulating hematopoietic stem cells (HSCs) and that reduction of osteoblasts does not affect HSC frequency, suggesting that other molecular pathways may also modulate the interaction of HSCs with their niches.     

Functional expression in mast cells of chimeric receptors with antibody specificity

Cell Biochemistry and Biophysics - Chimeric genes composed of a single-chain Fv domain (scFv) of an antibody linked with receptor chains normally present in cells of hematopoietic origin were...     

The origins of blood: induction of hematopoietic stem cells from different sources

Ex vivo hematopoiesis from embryonic sources offers exciting promises in basic research and medicine. In this issue of Cell Stem Cell, Ledran et al. (2008) describe human embryonic stem cell (hESC)-derived hematopoiesis, while Taoudi et al. (2008) define the origin of definitive hematopoietic stem cells (HSCs) from the mouse aorta-gonad-mesonephros (AGM) region.     

The complex cartography of stem cell commitment

In this issue of Cell, a study by Adolfsson and coworkers (Adolfsson et al., 2005) provides insight into the early lineage commitment events of multipotent hematopoietic stem cells (HSCs). These studies demonstrate the importance of the Flt3 receptor tyrosine kinase as the earliest marker of hematopoietic cell fate commitment in that erythrocyte and megakaryocyte potentials are lost first as HSCs differentiate to lymphocyte progenitors.     

Are Hematopoietic Stem Cells Generated in the Placenta?

In this issue of Cell Stem Cell, the origin of multipotent hematopoietic cells present in the placenta has been assessed in Ncx1(-/-) embryos lacking a functional heart and circulation. Rhodes and colleagues (Rhodes et al., 2008) found lymphoid progenitors in the placenta, as well as in dorsal aorta and yolk sac and vitelline vessels, indicating that they arose in situ.     

Cell therapy for inherited diseases of the hematopoietic system

Cell therapy was born in 1968 with the first allogeneic transplantation of hematopoietic stem cells for two immune deficiency disorders: the Wiskott-Aldrich syndrome and the Severe Combined ImmunoDeficiency (SCID). From this pioneering experience, thousands of patients affected with inherited or acquired diseases of the hematopoietic system have benefited from this therapeutic approach. Unfortunately, immunologic obstacles, represented by the compatibility in the major histocompatibility HLA system, still dictate today important limitations for a larger therapeutic utilization of hematopoietic stem cells (HSC). In this review, we have summarized the difficulties and the scientific advances leading us to improve the clinical results; the therapeutic research's track for primary immunodeficiencies is also discussed.     

Nervous activity in a stem cell niche

In this issue of Cell, report a new regulatory axis for the mobilization of hematopoietic stem cells that links these cells to the nervous system and bone in an unanticipated way. The new findings suggest that the nervous system, which has the inherent ability to integrate information from throughout the organism, may govern the local relationship between stem cells and their niches.     

Characterization of hematopoietic potential of mesenchymal stem cells

Mesenchymal and hematopoietic tissues are important reservoirs of adult stem cells. The potential of tissue resident mesenchymal stem cells (MSCs) to differentiate into cells of mesodermal and ectodermal lineages has been reported previously. We examined the hypothesis that adherent adipose tissue resident mesenchymal stem cells (ASCs) are capable of generating cells with hematopoietic characteristics. When cultured in differentiation media, clonally isolated ASCs develop into cells with hematopoietic attributes. The hematopoietic differentiated cells (HD) express early hematopoietic (c‐kit, PROM1, CD4) as well as monocyte/macrophage markers (CCR5, CD68, MRC1, CD11b, CSF1R). Additionally, HD cells display functional characteristics of monocyte/macrophages such as phagocytosis and enzymatic activity of α‐Naphthyl Acetate Esterase. HD cells are also responsive to stimulation by IL‐4 and LPS as shown by increased CD14 and HLA‐DRB1 expressions and release of IL‐2, IL10, and TNF. Taken together, this study characterizes the potential of ASCs to generate functional macrophages in vitro, and therefore paves way for their possible use in cell therapy applications. J. Cell. Physiol. 225: 888–897, 2010. © 2010 Wiley‐Liss, Inc.     

Disrupting the stem cell niche: good seeds in bad soil

Stem cells reside in a microenvironment or niche that is critical for stem cell maintenance and regulation. But what happens when a stem cell niche is disrupted? In this issue of Cell, two reports (Walkley et al., 2007a, 2007b) demonstrate in mice that alterations in the niche for hematopoietic stem cells lead to the development of myeloproliferative disease.