International immunopharmacology · 2025
H₂O₂ preconditioning enhances the transplantation-mediated therapeutic effect of bone marrow-derived mesenchymal stem cells after traumatic brain injury.
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Jiang En-Yan, Wang Kun, Zhang Qing-Zhou, Cui Zhi-Fei, Jiang Zong-Yuan, Gao Shuang-Qi, Chen Jun-Quan
Аннотация
BACKGROUND: Bone marrow mesenchymal stem cell (BMSC) transplantation has shown therapeutic potential in the treatment of traumatic brain injury (TBI). However, its efficacy is limited by the low survival rate of transplanted BMSCs within the brain microenvironment characterized by persistent inflammation and oxidative stress. Preconditioning BMSCs with low concentrations of hydrogen peroxide (H₂O₂) has been reported to enhance cell viability under oxidative stress. Nevertheless, the mechanisms by which H₂O₂ pretreatment enhances BMSC survival and the role of pretreated BMSCs in promoting functional recovery after TBI remain to be elucidated.
METHODS: BMSCs were exposed to varying concentrations of H₂O₂ to evaluate their proliferation, migration, and survival. The optimal concentration (50 μM) was selected for subsequent experiments. To investigate the underlying mechanisms, miRNA sequencing (miRNA-Seq) was performed. Differentially expressed microRNAs were identified using DESeq2, with a screening threshold of fold change ≥1.0 and p-value <0.05. A rat TBI model then established, and green fluorescent protein (GFP)-labeled BMSCs, either preconditioned with H₂O₂ or left untreated, were transplanted into the lesion site. The survival of BMSCs and the lesion volume in the TBI model were assessed using immunofluorescence and histopathological examination. Functional recovery in TBI rats was evaluated through a modified neurological severity score (mNSS) system and the rotarod test. The inflammatory response in the brain injury area was assessed using immunofluorescence and enzyme-linked immunosorbent assay (ELISA).
RESULTS: Low-dose H₂O₂ preconditioning significantly enhanced BMSCs proliferation, migration, and survival. miRNA analysis revealed that H₂O₂ treatment reduced the expression of miR-9a-5p, which in turn boosted BMSCs viability by increasing levels of a key survival protein, CXCR4. In vivo, H₂O₂-preconditioned BMSCs showed improved survival after transplantation, reduced inflammation, smaller lesion volumes, and better neurological recovery in TBI rats compared to non-preconditioned cells.
CONCLUSION: H₂O₂ preconditioning enhances the therapeutic effect of BMSC transplantation in TBI by improving cell survival and modulating inflammation. This strategy may offer a promising approach to improving the therapeutic efficacy of BMSCs in TBI treatment.
METHODS: BMSCs were exposed to varying concentrations of H₂O₂ to evaluate their proliferation, migration, and survival. The optimal concentration (50 μM) was selected for subsequent experiments. To investigate the underlying mechanisms, miRNA sequencing (miRNA-Seq) was performed. Differentially expressed microRNAs were identified using DESeq2, with a screening threshold of fold change ≥1.0 and p-value <0.05. A rat TBI model then established, and green fluorescent protein (GFP)-labeled BMSCs, either preconditioned with H₂O₂ or left untreated, were transplanted into the lesion site. The survival of BMSCs and the lesion volume in the TBI model were assessed using immunofluorescence and histopathological examination. Functional recovery in TBI rats was evaluated through a modified neurological severity score (mNSS) system and the rotarod test. The inflammatory response in the brain injury area was assessed using immunofluorescence and enzyme-linked immunosorbent assay (ELISA).
RESULTS: Low-dose H₂O₂ preconditioning significantly enhanced BMSCs proliferation, migration, and survival. miRNA analysis revealed that H₂O₂ treatment reduced the expression of miR-9a-5p, which in turn boosted BMSCs viability by increasing levels of a key survival protein, CXCR4. In vivo, H₂O₂-preconditioned BMSCs showed improved survival after transplantation, reduced inflammation, smaller lesion volumes, and better neurological recovery in TBI rats compared to non-preconditioned cells.
CONCLUSION: H₂O₂ preconditioning enhances the therapeutic effect of BMSC transplantation in TBI by improving cell survival and modulating inflammation. This strategy may offer a promising approach to improving the therapeutic efficacy of BMSCs in TBI treatment.