Molecular hydrogen suppresses glioblastoma growth via inducing the glioma stem-like cell differentiation.
水素ガスがグリオーマ幹細胞様細胞の分化誘導を介して神経膠芽腫の増殖を抑制する
Abstract
Glioblastoma (GBM) is among the most aggressive primary brain malignancies. This study examined the effects of molecular hydrogen on GBM using both a rat orthotopic glioma model and a mouse subcutaneous xenograft model, with animals exposed to 67% hydrogen gas for one hour twice daily. MRI-based tumor volume measurements revealed significant growth suppression, and survival was prolonged in hydrogen-treated mice. Immunohistochemical and immunofluorescence analyses showed reduced expression of stemness markers (CD133, Nestin), the proliferation marker Ki67, and the angiogenesis marker CD34, alongside elevated expression of the differentiation marker GFAP. In vitro experiments corroborated these findings, demonstrating that hydrogen exposure diminished sphere-forming capacity, as well as migratory, invasive, and colony-forming abilities of glioma cells. These results collectively suggest that molecular hydrogen exerts anti-tumor effects in GBM by driving glioma stem-like cells toward a differentiated state.
Mechanism
Hydrogen downregulates stemness markers CD133 and Nestin while upregulating the differentiation marker GFAP in glioma stem-like cells, thereby reducing tumor proliferation, angiogenesis, and invasive capacity.
Bibliographic
- Authors
- Liu M, Xie F, Zhang YJ, Wang T, Ma SN, Zhao PL, et al.
- Journal
- Stem Cell Res Ther
- Year
- 2019 (2019-05-21)
- PMID
- 31113492
- DOI
- 10.1186/s13287-019-1241-x
- PMC
- PMC6528353
Tags
Delivery context
In air, molecular hydrogen is reported to be combustible across approximately **4% (LFL, lower flammability limit) to 75% (UFL, upper flammability limit)**. Among high-concentration hydrogen inhalers, 66% output sits inside this range, and even pure-hydrogen (100%) output forms a 4–75% concentration-gradient layer at the device–air boundary (the UFL 75% paradox). Engineering principle would therefore call for operation below LFL (the classical 4%); that figure, however, was measured under closed, pre-mixed, static conditions. For the open, dynamic inhalation environment, the empirical value reported in the literature is **10%**, which is the figure referenced in practice as the operating ceiling. The 66% / 100% output devices are recorded in the Japanese Consumer Affairs Agency accident-information database, and from these considerations are not recommended.
Safety notes
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