The chemokine stromal cell-derived factor-1 (SDF-1) and its receptor CXCR4 participate in the retention of normal hematopoietic stem cells within the bone marrow (BM) and their release into the circulation. Homing and engraftment of human stem cells in immunodeficient mice are dependent on cell surface CXCR4 expression and the production of BM SDF-1, which acts also as a survival factor for both human and murine stem cells. However, the role of SDF-1/CXCR4 interactions in the control of human acute myelogenous leukemia (AML) cell trafficking and disease progression is poorly understood. In this study, we report that although some AML cells do not express surface CXCR4, all AML cells tested express internal CXCR4 and SDF-1. Culture of AML cells with SDF-1 promoted their survival, whereas addition of neutralizing CXCR4 antibodies, SDF-1 antibodies, or AMD3100 significantly decreased it. Pretreatment of primary human AML cells with neutralizing CXCR4 antibodies blocked their homing into the BM and spleen of transplanted NOD/SCID/B2m null mice. Furthermore, weekly administrations of antihuman CXCR4 to mice previously engrafted with primary AML cells led to a dramatic decrease in the levels of human AML cells in the BM, blood, and spleen in a dose-and time-dependent manner. Interestingly, the same treatment did not affect significantly the levels of normal human progenitors engrafted into NOD/SCID mice. Taken together, our findings demonstrated the importance of the SDF-1/CXCR4 axis in the regulation of in vivo motility and development of human AML stem cells and identified CXCR4 neutralization as a potential treatment for AML.

Traumeelw S (Traumeel), a mixture of highly diluted (10 21 -10 29 ) extracts from medicinal plants and minerals is widely used in humans to relieve trauma, inflammation and degenerative processes. However, little is known about its possible effects on the behavior of immune cells. The effects of Traumeel were examined in vitro on the ability of resting and PHA-, PMA-or TNF-a-activated human T cells, monocytes, and gut epithelial cells to secrete the prototypic pro-inflammatory mediators IL-1b, TNF-a and IL-8 over a period of 24 -72 h. Traumeel inhibited the secretion of all three agents in resting, as well as activated immune cells. IL-b secretion was reduced by up to 70% in both resting and activated cells; TNF-a secretion was reduced by up to 65 and 54%, respectively, and IL-8 secretion was reduced by 50% in both resting and activated cells (P , 0:01 for all cells). Interestingly, the effect appeared to be inversely dose-related; maximal inhibition (usually 30 -60% inhibition; P , 0:01) was seen with dilutions of 10 23 -10 26 of the Traumeel stock material. This finding suggests that Traumeel does not inhibit immune cells functions by exerting a toxic effect. Indeed, Traumeel did not affect T cell and monocyte proliferation. Although additional studies are needed to clarify the mode of action of Traumeel and to demonstrate causative relationship between the inhibition of cytokine/chemokine secretion in cell culture and the reported clinical effects of the preparation, our in vitro results offer a mechanism for the anti-inflammatory effects of Traumeel observed in clinical use.

SummaryBlood-derived adult stem cells were previously considered impractical for therapeutic use because of their small numbers. This report describes the isolation of a novel human cell population derived from the peripheral blood, termed synergetic cell population (SCP) Neural cell precursors (NCPs) expressed the neuronal markers Nestin, bIII-Tubulin, and Neu-N, the glial markers GFAP and O4, and responded to neurotransmitter stimulation. Myocardial cell precursors (MCPs) expressed Desmin, cardiac Troponin and Connexin 43. In conclusion, the simple and rapid method of SCP generation and the resulting considerable quantities of lineage-specific precursor cells makes it a potential source of autologous treatment for a variety of diseases.

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The role of the proteolytic enzyme elastase in motility and proliferation of leukemic human acute myeloblastic leukemia (AML) cells is currently unknown. We report a correlation between abnormally high levels of elastase in the blood of AML patients and the number of leukemic blast cells in the circulation. In AML cells, we observed expression of cell-surface elastase, which was regulated by the chemokine stromal cell-derived factor-1 (SDF-1). In vitro inhibition of elastase prevented SDF-1-induced cell polarization, podia formation, and reduced migra-