Vascular endothelial growth factor (VEGF) is pivotal for blood vessel formation and haematopoiesis, but its effect on stem cells has remained unclear. In 27 June Nature, Hans-Peter Gerber and colleagues from Genentech Inc., San Francisco, show that VEGF regulates haematopoietic stem cell (HSC) survival by an internal autocrine loop mechanism (Nature 2002, 417:954-958).

Gerber et al. transplanted normal bone marrow cells, or cells in which the VEGF gene had been deleted into irradiated wild-type mice. They observed that HSCs deficient in VEGF showed reduced survival, colony formation and in vivo repopulation rates.

They also observed that only VEGF inhibitors acting intracellularly mimicked the deletion of the VEGF gene; blocking VEGF by extracellular mechanisms had only minor effects. Ligands selective for VEGF and VEGFR-2 and also a VEGF receptor agonist could rescue survival and repopulation of VEGF-deficient HSCs.

"The discovery of an autocrine loop formed by...

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