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 (.NO) dependent mechanism. The population of CD34+ cells in the peripheral circulation of humans (n=23) doubled in response to a single exposure to 2.0 atmospheres absolute (ATA) O2 for 2 hours. Over a course of twenty treatments, circulating CD34+ cells increased eightfold, although the over‐all 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+ sub‐population, but increased cell growth only occurred in samples obtained immediately post‐treatment. 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 1008 + 255 nM in association with HBO2. Stem cell mobilization did not occur in knock out mice lacking genes for endothelial .NO synthase. Moreover, pre‐treatment of wild type mice with a nitric oxide (.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. Supported by NIH grant AT00428.