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Regulation and Function of Stem Cells in the Cardiovascular System

Stem cell mobilization by hyperbaric oxygen

¹Institute for Environmental Medicine and Departments of ²Emergency Medicine, ³Surgery, and ⁴Physiology, 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 (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.

nitric oxide; CD34; CD133; CXCR4; cKit; colony-forming cells; progenitor cells

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