100% oxygen mobilizes stem cells and up-regulates MIF and APRIL in humans: a new point on the hormetic dose curve

IntroductionThe aim of the current study was to test normobaric 100% oxygen (NBO) (PiO2 = 713 mmHg) for stem cell mobilization and cytokine modulation. Although current oxygen therapy (PiO2 = 1,473–2,233 mmHg) is well known to mobilize stem cells and modulate cytokine, little is known about NBO and...

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Main Authors: Kent J. MacLaughlin, Gregory P. Barton, Julia E. MacLaughlin, Jacob J. Lamers, Matthew D. Marcou, Matthew J. O’Brien, Rudolf K. Braun, Marlowe W. Eldridge
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-02-01
Series:Frontiers in Cell and Developmental Biology
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Online Access:https://www.frontiersin.org/articles/10.3389/fcell.2024.1377203/full
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author Kent J. MacLaughlin
Gregory P. Barton
Julia E. MacLaughlin
Jacob J. Lamers
Matthew D. Marcou
Matthew J. O’Brien
Rudolf K. Braun
Marlowe W. Eldridge
author_facet Kent J. MacLaughlin
Gregory P. Barton
Julia E. MacLaughlin
Jacob J. Lamers
Matthew D. Marcou
Matthew J. O’Brien
Rudolf K. Braun
Marlowe W. Eldridge
author_sort Kent J. MacLaughlin
collection DOAJ
description IntroductionThe aim of the current study was to test normobaric 100% oxygen (NBO) (PiO2 = 713 mmHg) for stem cell mobilization and cytokine modulation. Although current oxygen therapy (PiO2 = 1,473–2,233 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.MethodsHealthy 30–35-year-old volunteers were exposed to 100% normobaric oxygen for 60 min, 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).ResultsCD45dim/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 downregulated 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.ConclusionThis study demonstrates that 100% normobaric oxygen mobilizes stem cells and upregulates the expression of the inflammatory cytokines marking a new point on the low dose stimulation phase of the hormetic dose curve of oxygen.
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spelling doaj-art-e013c0053a8a41478f5d7ea5774f2e422025-02-05T07:32:59ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2025-02-011210.3389/fcell.2024.13772031377203100% oxygen mobilizes stem cells and up-regulates MIF and APRIL in humans: a new point on the hormetic dose curveKent J. MacLaughlin0Gregory P. Barton1Julia E. MacLaughlin2Jacob J. Lamers3Matthew D. Marcou4Matthew J. O’Brien5Rudolf K. Braun6Marlowe W. Eldridge7Department of Pediatrics, University of Wisconsin, Madison, WI, United StatesDepartment of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, United StatesMedical Oxygen Hyperbaric Clinic, The American Center, Madison, WI, United StatesDepartment of Pediatrics, University of Wisconsin, Madison, WI, United StatesDepartment of Pediatrics, University of Wisconsin, Madison, WI, United StatesUniversity of Wisconsin School of Medicine and PublicHealth, Madison, WI, United StatesDepartment of Pediatrics, University of Wisconsin, Madison, WI, United StatesDepartment of Pediatrics, University of Wisconsin, Madison, WI, United StatesIntroductionThe aim of the current study was to test normobaric 100% oxygen (NBO) (PiO2 = 713 mmHg) for stem cell mobilization and cytokine modulation. Although current oxygen therapy (PiO2 = 1,473–2,233 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.MethodsHealthy 30–35-year-old volunteers were exposed to 100% normobaric oxygen for 60 min, 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).ResultsCD45dim/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 downregulated 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.ConclusionThis study demonstrates that 100% normobaric oxygen mobilizes stem cells and upregulates the expression of the inflammatory cytokines marking a new point on the low dose stimulation phase of the hormetic dose curve of oxygen.https://www.frontiersin.org/articles/10.3389/fcell.2024.1377203/fulloxygen therapystem cell mobilization and hominginflammatory cyotokinesmacrophage migration inhibition factorhematopoietic (stem cell) transplant (HSCT)proangiogenic
spellingShingle Kent J. MacLaughlin
Gregory P. Barton
Julia E. MacLaughlin
Jacob J. Lamers
Matthew D. Marcou
Matthew J. O’Brien
Rudolf K. Braun
Marlowe W. Eldridge
100% oxygen mobilizes stem cells and up-regulates MIF and APRIL in humans: a new point on the hormetic dose curve
Frontiers in Cell and Developmental Biology
oxygen therapy
stem cell mobilization and homing
inflammatory cyotokines
macrophage migration inhibition factor
hematopoietic (stem cell) transplant (HSCT)
proangiogenic
title 100% oxygen mobilizes stem cells and up-regulates MIF and APRIL in humans: a new point on the hormetic dose curve
title_full 100% oxygen mobilizes stem cells and up-regulates MIF and APRIL in humans: a new point on the hormetic dose curve
title_fullStr 100% oxygen mobilizes stem cells and up-regulates MIF and APRIL in humans: a new point on the hormetic dose curve
title_full_unstemmed 100% oxygen mobilizes stem cells and up-regulates MIF and APRIL in humans: a new point on the hormetic dose curve
title_short 100% oxygen mobilizes stem cells and up-regulates MIF and APRIL in humans: a new point on the hormetic dose curve
title_sort 100 oxygen mobilizes stem cells and up regulates mif and april in humans a new point on the hormetic dose curve
topic oxygen therapy
stem cell mobilization and homing
inflammatory cyotokines
macrophage migration inhibition factor
hematopoietic (stem cell) transplant (HSCT)
proangiogenic
url https://www.frontiersin.org/articles/10.3389/fcell.2024.1377203/full
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