Stem cell factor augments tumor necrosis factor-granulocyte-macrophage colony-stimulating factor-mediated dendritic cell hematopoiesis

Stem Cells
F Santiago-SchwarzS E Carsons

Abstract

We describe the effects of stem cell factor (SCF) on the dendritic cell (DC) pathway and provide evidence for the existence of a post granulocyte-macrophage colony-forming unit (GM-CFU) DC progenitor. When employed with cytokines regulating DC development (tumor necrosis factor [TNF] + GM colony-stimulating factor [GM-CSF]), SCF increased the size of monocyte (mono) and mono-DC colonies arising from cord blood CD34+ progenitor cells. The overall plating efficiency of these colonies increased approximately threefold, as compared with growth in TNF + GM-CSF. Most (approximately 70%) of the CFUs were mono-DC CFU, and SCF did not alter the proportion of mono-DC CFU to mono-CFU obtained with TNF + GM-CSF alone. Proliferation, as measured by thymidine uptake and manual cell counts, at least doubled and occurred earlier (by day 4). In long-term cultures established with TNF + GM-CSF + SCF, high levels of proliferation were prolonged for up to three weeks. These were associated with extended DC development and the capacity to form 2 degree mono-DC colonies. There was no induction of polymorphonuclear (PMN) cells in 2 degree cultures treated with either GM-CSF, GM-CSF + SCF or GM-CSF + granulocyte CSF (G-CSF), implying that the DC proge...Continue Reading

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