Stem cell mobilization by hyperbaric oxygen

We hypothesized that exposure to hyperbaric oxygen (HBO2) would mobilize stem/progenitor cells from the bone marrow by a nitric oxide (center dot NO)-dependent mechanism. The population of CD34(+) cells in the peripheral circulation of humans doubled in response to a single exposure to 2.0 atmospheres absolute (ATA) O-2 for 2 h. Over a course of 20 treatments, circulating CD34(+) cells increased eightfold, although the overall circulating white cell count was not significantly increased. The number of colony-forming cells (CFCs) increased from 16 +/- 2 to 26 +/- 3 CFCs/100,000 monocytes plated. Elevations in CFCs were entirely due to the CD34(+) subpopulation, but increased cell growth only occurred in samples obtained immediately posttreatment. A high proportion of progeny cells express receptors for vascular endothelial growth factor-2 and for stromal-derived growth factor. In mice, HBO2 increased circulating stem cell factor by 50%, increased the number of circulating cells expressing stem cell antigen-1 and CD34 by 3.4-fold, and doubled the number of CFCs. Bone marrow center dot NO concentration increased by 1,008 +/- 255 nM in association with HBO2. Stem cell mobilization did not occur in knockout mice lacking genes for endothelial center dot NO synthase. Moreover, pretreatment of wild-type mice with a center dot NO synthase inhibitor prevented the HBO2-induced elevation in stem cell factor and circulating stem cells. We conclude that HBO2 mobilizes stem/progenitor cells by stimulating center dot NO synthesis.