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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Enhanced growth of megakaryocyte colonies in culture in the presence of heparin and fibroblast growth factor.

Fibroblast growth factors (FGFs) are a family of mitogenic proteins that promote the division of most mesoderm- and neuroectoderm-derived cells. Interaction with heparin-like molecules appears to be critical for FGFs to exert their activity. We previously reported that FGF-1, FGF-2, and heparin are each capable of stimulating megakaryocytopoiesis in vitro and that heparin has a thrombopoietic effect when administered to patients with chronic immune thrombocytopenic purpura. The present study was designed to determine whether the combination of heparin and FGF results in a synergistic effect on murine megakaryocytopoiesis. In vitro, in both plasma clot and agar serum-free culture systems, FGF-1 and FGF-2 stimulated megakaryocyte colony formation in a dose-dependent fashion. Half-maximal effect of the two FGFs was observed at 1 ng/ml, and their effect was saturating at 20 ng/ml. The addition of heparin to cultures stimulated by FGF-1 or FGF-2 resulted in a 2-fold increase in the number of megakaryocyte colonies compared to the culture containing FGF alone. In the presence of heparin (5 IU/ml), FGF at 1 ng/ml exerted an almost maximal stimulating effect on megakaryocyte colony formation. When murine and human CD34+ cells were used as target cells, a similar interaction between FGF and heparin was observed. The combination of FGF and heparin induced a maximal growth of megakaryocyte colonies from CD34+ cells. These findings demonstrate the synergistic effect of heparin and FGF on megakaryocytopoiesis.[1]


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