# 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](https://pubmed.ncbi.nlm.nih.gov/31113492/)
- **DOI**: [10.1186/s13287-019-1241-x](https://doi.org/10.1186/s13287-019-1241-x)
- **PMC**: [PMC6528353](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6528353/)
- **Study type**: animal study
- **Delivery route**: inhalation
- **Effect reported**: positive
- **H2 concentration**: 67%

## Delivery context

For inhalation applications of molecular hydrogen, the lower flammability limit (LFL) deserves careful handling. The classical 4% figure applies to closed-system mixtures; the practical inhalation-environment threshold is 10%. Even pure-hydrogen output (the UFL 75% paradox) passes through the flammable range at the air–gas boundary. High-concentration (66% / 100%) inhalers are documented in the Japanese Consumer Affairs Agency accident-information database and are not recommended.

## Safety notes

For inhalation applications of molecular hydrogen, the lower flammability limit (LFL) deserves careful handling. The classical 4% figure applies to closed-system mixtures; the practical inhalation-environment threshold is 10%. Even pure-hydrogen output (the UFL 75% paradox) passes through the flammable range at the air–gas boundary. High-concentration (66% / 100%) inhalers are documented in the Japanese Consumer Affairs Agency accident-information database and are not recommended.

See also:
- [Inhalation concentration and LFL / UFL](https://h2-papers.org/en/safety-notes/inhalation-concentration)
- [Consumer Affairs Agency accident cases](https://h2-papers.org/en/safety-notes/accident-cases)
- [LFL / UFL terminology](https://h2-papers.org/en/safety-notes/lfl-ufl-explained)
- [Inhalation safety threshold lineage](https://h2-papers.org/en/safety-notes/lineage)

---

> **Cite as**: H2 Papers — PMID 31113492. https://h2-papers.org/en/papers/31113492
> **Source**: PubMed PMID [31113492](https://pubmed.ncbi.nlm.nih.gov/31113492/)