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100%氧气可动员人类干细胞并上调巨噬细胞移动抑制因子（MIF）和增殖诱导配体（APRIL）：应激剂量曲线上的一个新点。

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

作者信息

MacLaughlin Kent J, Barton Gregory P, MacLaughlin Julia E, Lamers Jacob J, Marcou Matthew D, O'Brien Matthew J, Braun Rudolf K, Eldridge Marlowe W

机构信息

Department of Pediatrics, University of Wisconsin, Madison, WI, United States.

Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, United States.

出版信息

Front Cell Dev Biol. 2025 Feb 5;12:1377203. doi: 10.3389/fcell.2024.1377203. eCollection 2024.

DOI:10.3389/fcell.2024.1377203
PMID:39974348
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11836035/
Abstract

INTRODUCTION

The 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.

METHODS

Healthy 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).

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 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.

CONCLUSION

This 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.

摘要

引言

本研究的目的是测试常压100%氧气（NBO）（吸入氧分压=713 mmHg）对干细胞动员和细胞因子调节的作用。尽管目前已知的氧气疗法（吸入氧分压=1473 - 2233 mmHg）能促进干细胞动员并调节细胞因子，但对于常压100%氧气及其在氧气应激剂量曲线低剂量刺激阶段的作用却知之甚少。我们提出一个问题，常压100%氧气能否动员干细胞并调节细胞因子。如果结果呈阳性，就有可能制定和完善氧气治疗方案、扩大治疗途径并优化患者治疗效果。

方法

选取30 - 35岁的健康志愿者，周一至周五每天暴露于常压100%氧气中60分钟，共进行2周，10次暴露。在四个时间点采集静脉血样本：1）首次暴露前（作为每个受试者的对照）；2）首次暴露后立即采集（测量急性效应）；3）第九次暴露前立即采集（测量慢性效应）；4）最后一次暴露后三天采集（评估持续性）。不知情的科学家使用流式细胞术对干祖细胞（SPCs）进行门控和定量分析。

结果

在每日1小时暴露于常压100%氧气9天后，CD45dim/CD34+/CD133+和CD45+/CD34+/CD133+细胞显著动员。相反，CD45-/CD34+/CD133+、CD45-/CD34+/CD133-和CD45-/CD34-/CD133+表型下调，表明其分化为更成熟的表型。CD133+表型显示从CD45-干细胞向CD45dim干细胞成熟。CD45-/CD34、CD45-/CD31和CD45-/CD105下调，而相关的CD45dim和CD45表型无变化。细胞因子“巨噬细胞迁移抑制因子”（MIF）和“增殖诱导配体”（APRIL）显著上调。

结论

本研究表明，常压100%氧气可动员干细胞并上调炎性细胞因子的表达，这在氧气应激剂量曲线的低剂量刺激阶段标志着一个新的点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2801/11836035/3cbaf9d597c7/fcell-12-1377203-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2801/11836035/adf6e7c17b62/fcell-12-1377203-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2801/11836035/545742ff87e6/fcell-12-1377203-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2801/11836035/182db9787be9/fcell-12-1377203-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2801/11836035/3cbaf9d597c7/fcell-12-1377203-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2801/11836035/adf6e7c17b62/fcell-12-1377203-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2801/11836035/545742ff87e6/fcell-12-1377203-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2801/11836035/182db9787be9/fcell-12-1377203-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2801/11836035/3cbaf9d597c7/fcell-12-1377203-g004.jpg

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