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Untersuchte Arbeit:
Seite: 12, Zeilen: 1 ff.
Quelle: Smith 2003
Seite(n): Internet, Zeilen: Internet
[For example, the chemokine SDF-1 (which binds the receptor CCXR4) is essential

for trafficking of hematopoietic cells in the developing embryo, mediating] homing of HSC and progenitors to the bone marrow following transplantation and, in stem cell mobilization, for collecting peripheral blood stem cells for transplant purposes [31]. A number of other chemokines likely play important roles in hematopoiesis and are under active investigation.

HSC and progenitors bind tightly to a number of ECM components including heparin sulfates, chemokines, collagens, laminin, thrombospondin-1, fibronectin, and others. These molecules provide a scaffold for colocalizing progenitors and HSC with a wide array of positive and negative cytokines and other growth regulators. In addition, ECM and stromal components may directly mediate signaling to HSC to activate growth, protect cells from apoptosis, or modulate responses to positive and negative regulatory factors. The adhesion molecules on HSC and progenitors that mediate binding to these ECM components include CD44, integrins, selectins, and mucins. Adherence of cells to microenvironmental elements can trigger a variety of signaling pathways and can lead to changes in intracellular ions such as proton (pH), calcium, and the small GTPase Rho as well as lipid mediators such as phosphoinositides, diacylglycerol, and arachidonic acid metabolites [35]. Adhesion may also regulate expression of immediate-early genes such as c-fos and key cell cycle events such as kinase activity of cyclin-cdk complexes and phosphorylation of the retinoblastoma (Rb) protein [36]. Cell adhesion may potentiate the responses to growth factors and by modulating the downstream components of growth factor signaling cascades including PI-3 kinase, AKT, and p70rsk [37]. Hematopoietic and non-hematopoietic cells that may regulate hematopoiesis include NK cells, T cells, macrophages, fibroblasts, osteoblasts, adipocytes, and perhaps even neurons [38, 39]. These cells may produce important growth factors, facilitate engraftment, or induce apoptosis. A number of nutrients, trace elements, and vitamins (zinc, selenium, copper, vitamins A, D, and E) are also critical to hematopoiesis. Retinoids and particularly retinoid antagonists play important roles in differentiation at even low concentrations.

For example, the chemokine SDF-1 (which binds the receptor CCXR4) is essential for trafficking of hematopoietic cells in the developing embryo, mediating homing of HSCs and progenitors to the bone marrow following transplantation and, in stem cell mobilization, for collecting peripheral blood stem cells for transplant purposes.[47] A number of other chemokines likely play important roles in hematopoiesis and are under active investigation.

Other important environmental regulators of hematopoiesis include the ECM components, other hematopoietic and nonhematopoietic cells, nutrients and vitamins, and a variety of physiologic processes. HSCs and progenitors bind tightly to a number of ECM components including heparin sulfates, chemokines, collagens, laminin, thrombospondin-1, fibronectin, and others. These molecules provide a scaffold for colocalizing progenitors and HSCs with a wide array of positive and negative cytokines and other growth regulators. In addition, ECM and stromal components may directly mediate signaling to HSCs to activate growth, protect cells from apoptosis, or modulate responses to positive and negative regulatory factors. The adhesion molecules on HSCs and progenitors that mediate binding to these ECM components include integrins, selectins, and mucins. Adherence of cells to microenvironmental elements can trigger a variety of signaling pathways and can lead to changes in intra-cellular ions such as proton (pH), calcium, and the small GTPase Rho as well as lipid mediators such as phosphoinositides, diacylglycerol, and arachidonic acid metabolites.[51] Adhesion may also regulate expression of immediate-early genes such as c-fos and key cell cycle events such as kinase activity of cyclincdk complexes and phosphorylation of the retinoblastoma (Rb) protein.[52] Cell adhesion may potentiate the responses to growth factors and by modulating the downstream components of growth factor signaling cascades including PI 3 kinase, AKT, and p70rsk.[53] Hematopoietic and nonhematopoietic cells that may regulate hematopoiesis include NK cells, T cells, macrophages, fibroblasts, osteoblasts, adipocytes, and perhaps even neurons.[54,55] These cells may produce important growth factors, facilitate engraftment, or induce apoptosis. A number of nutrients, trace elements, and vitamins (eg, zinc, selenium, copper, vitamins A, D, and E) are also critical to hematopoiesis. Retinoids and particularly retinoid antagonists play important roles in differentiation at even low concentrations.

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