We hypothesized that exposure tohyperbaric oxygen (HBO2) would mobilize stem/progenitor cells from the bone marrow by a nitric oxide from the bone marrow by a nitric oxide ( NO) -dependent mechanism.The population of CD34 cells in the peripheral circulation of humansdoubled 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 cellcount was not significantly increased. The number of colony-formingcells (CFCs) increased from 16 2 to 26 3 CFCs/100,000monocytes plated. Elevations in CFCs were entirely due to the CD34 subpopulation, but increased cell growth only occurred in samplesobtained immediately posttreatment. A high proportion of progenycells express receptors for vascular endothelial growth factor-2 andfor stromal-derived growth factor. In mice, HBO2 increased circulatingstem cell factor by 50%, increased the number of circulating cellsexpressing stem cell antigen-1 and CD34 by 3.4-fold, and doubled thenumber of CFCs. Bone marrow NO concentration increased by1,008 255 nM in association with HBO2. Stem cell mobilization didnot occur in knockout mice lacking genes for endothelial NO synthase.Moreover, pretreatment of wild-type mice with a NO synthaseinhibitor prevented the HBO2-induced elevation in stem cell factorand circulating stem cells. We conclude that HBO2 mobilizes stem/progenitor cells by stimulating NO synthesis.
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