Effect of intermittent hyperoxia on stem cell mobilization and cytokine expression

The best known form of oxygen therapy is hyperbaric oxygen (HBO) therapy, which increases both concentration and atmospheric pressure. HBO supports tissue regeneration and is indicated in an increasing number of pathologies. Less known but still showing some promising effects is normobaric oxygen (NBO) therapy, which provides some advantages over HBO including eliminating barotrauma risk, increased ease of administration and a significant cost reduction. However, still little is known about differences and similarities in treatment effects between HBO and NBO. Therefore we tested whether NBO induces a biological response comparable to HBO with a focus on stem progenitor cell mobilization and changes in serum cytokine concentration. We randomly assigned Sprague-Dawley rats into an NBO treatment group (n = 6), and a room air control group (n = 6). The NBO treatment group was exposed to 42% oxygen for 2 hours a day for 10 days. The room air group was concurrently kept at 20.9% oxygen. The frequency and number of stem progenitor cells in peripheral blood were analyzed by flow cytometry. Plasma cytokine expression was analyzed by cytokine array enzyme linked immunosorbent assay. All analyses were performed 24 hours after the final exposure to control for transient post treatment effects. The NBO treatment group showed an increase in circulating CD133⁺/CD45⁺ stem progenitor cell frequency and number compared to the room air control group. This rise was largely caused by CD34^- stem progenitor cells (CD133⁺/CD34^-/CD45⁺) without changes in the CD34⁺ population. The plasma cytokine levels tested were mostly unchanged with the exception of tumor necrosis factor-α which showed a decrease 24 hours after the last NBO exposure. These findings support our hypothesis that NBO induces a biological response similar to HBO, affecting serum stem progenitor cell populations and tumor necrosis factor-α concentration. The study was approved by Institutional Animal Care and Use Committee (IACUC) of the University of Wisconsin, Madison, WI, USA (approval No. M005439) on June 28, 2016.