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ORIGINAL RESEARCH article

Front. Cell Dev. Biol.
Sec. Stem Cell Research
Volume 12 - 2024 | doi: 10.3389/fcell.2024.1377203

Stem cell mobilization and cytokine modulation in humans by 100% oxygen; a new point on the hormetic dose curve

Provisionally accepted
Kent J. MacLaughlin Kent J. MacLaughlin 1,2*Gregory P Barton Gregory P Barton 3Julia E Maclaughlin Julia E Maclaughlin 4Jacob Lamers Jacob Lamers 1Matthew Marcou Matthew Marcou 1Matthew J O'brien Matthew J O'brien 1Rudolf Karl Braun Rudolf Karl Braun 1Marlowe W Eldridge Marlowe W Eldridge 1
  • 1 University of Wisconsin-Madison, Madison, Wisconsin, United States
  • 2 Department of Pediatrics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, United States
  • 3 Medical School, University of Texas Southwestern Medical Center, Dallas, Texas, United States
  • 4 Medical Oxygen Hyperbaric Clinic and Research Center, Madison, United States

The final, formatted version of the article will be published soon.

    Introduction: The aim of the current study was to test normobaric 100% oxygen (NBO) (PiO2=713mmHg) for stem cell mobilization and cytokine modulation. Although current oxygen therapy (PiO2=1473 to 2233 mmHg) is well known to mobilize stem cells and modulate cytokine, little is known about NBO and its place on the low dose stimulation phase of the hormetic dose curve of oxygen. We asked the question, will NBO mobilize stem cells and modulate cytokines. A positive outcome presents the potential to create and refine oxygen treatment protocols, expand access, and optimize patient outcomes. Methods: Healthy 34–35-year-old volunteers were exposed to 100% normobaric oxygen for 60 minutes, M-F, for 10 exposures over 2 weeks. Venous blood samples were collected at four time points: (1) prior to the first exposure (serving as the control for each subject), (2) immediately after the first exposure (to measure the acute effect), (3) immediately before the ninth exposure (to measure the chronic effect), and (4) three days after the final exposure (to assess durability). Blinded scientists used flow cytometry to gate and quantify the Stem Progenitor Cells (SPCs). Results: CD45dim/CD34+/CD133+ and CD45+/CD34+/CD133+ were significantly mobilized following nine daily one-hour exposures to normobaric 100% oxygen. Conversely CD45-/CD34+/CD133+, CD45-/CD34+/CD133- and CD45-/CD34-/CD133+ phenotypes were downregulated suggesting differentiation into more mature phenotypes. The CD133+ phenotype exhibited a maturing from CD45- to CD45dim stem cells. CD45-/CD34, CD45-/CD31 and CD45-/CD105 were down-regulated with no changes in related CD45dim and CD45+ phenotypes. The cytokines “macrophage migration inhibitory factor" (MIF) and “a proliferation inducing ligand” (APRIL) were significantly upregulated. Conclusions: This study demonstrates that 100% normobaric oxygen mobilizes stem cells and upregulates the expression of inflammatory cytokines marking a new point on the low dose stimulation phase of the hormetic dose curve of oxygen.

    Keywords: Oxygen therapy, Stem cell mobilization and homing, Inflammatory cyotokines, Macrophage migration inhibition factor, hematopoietic (stem cell) transplant (HSCT), Proangiogenic, A proliferation inducing ligand (APRIL), hemangioblast differentiation

    Received: 02 Feb 2024; Accepted: 26 Dec 2024.

    Copyright: © 2024 MacLaughlin, Barton, Maclaughlin, Lamers, Marcou, O'brien, Braun and Eldridge. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Kent J. MacLaughlin, University of Wisconsin-Madison, Madison, 53715-1149, Wisconsin, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.