Professor Stephen R. Thom, MD, PhD., et al. Institute for Environmental Medicine and Departments of Emergency Medicine, Surgery, and Physiology, University of Pennsylvania Medical Center, Philadelphia. Am J Physiol Heart Circ Physiol 290: H1378-H1386, 2006. Nov 18 2005; doi:10.1152/ajpheart.00888.2005
We hypothesized that exposure to hyperbaric oxygen (HBO2) would mobilize stem/progenitor cells from the bone marrow by a nitric oxide (∑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) O2 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 ∑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 ∑NO synthase. Moreover, pretreatment of wild-type mice with a ∑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 ∑NO synthesis.
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