Stem cell mobilization by hyperbaric oxygen

1 Institute for Environmental Medicine and Departments of 2 Emergency Medicine, 3 Surgery, and 4 Physiology, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania Submitted 19 August 2005 ; accepted in final form 7 November 2005 We hypothesized that exposure to hyperbaric oxygen (HBO 2 ) 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) 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, HBO 2 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 HBO 2 . 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 HBO 2 -induced elevation in stem cell factor and circulating stem cells. We conclude that HBO 2 mobilizes stem/progenitor cells by stimulating ·NO synthesis. nitric oxide; CD34; CD133; CXCR4; cKit; colony-forming cells; progenitor cells Address for reprint requests and other correspondence: S. R. Thom, Institute for Environmental Medicine, Univ. of Pennsylvania, 1 John Morgan Bldg., 3620 Hamilton Walk, Philadelphia, PA 19104-6068 (e-mail: sthom{at}mail.med.upenn.edu )