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Pretreated MSCs with IronQ Transplantation Attenuate Microglia Neuroinflammation via the cGAS-STING Signaling Pathway
Guoqiang Yang1,2,3, Jiraporn Kantapan3, Maryam Mazhar4,5
1Research Center for Integrated Chinese and Western Medicine, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, People's Republic of China.
Background:
Intracerebral hemorrhage (ICH), a devastating form of stroke, is characterized by elevated morbidity and mortality rates. Neuroinflammation is a common occurrence following ICH. Mesenchymal stem cells (MSCs) have exhibited potential in treating brain diseases due to their anti-inflammatory properties. However, the therapeutic efficacy of MSCs is limited by the intense inflammatory response at the transplantation site in ICH. Hence, enhancing the function of transplanted MSCs holds considerable promise as a therapeutic strategy for ICH. Notably, the iron-quercetin complex (IronQ), a metal-quercetin complex synthesized through coordination chemistry, has garnered significant attention for its biomedical applications. In our previous studies, we have observed that IronQ exerts stimulatory effects on cell growth, notably enhancing the survival and viability of peripheral blood mononuclear cells (PBMCs) and MSCs. This study aimed to evaluate the effects of pretreated MSCs with IronQ on neuroinflammation and elucidate its underlying mechanisms.
Methods:
The ICH mice were induced by injecting the collagenase I solution into the right brain caudate nucleus. After 24 hours, the ICH mice were randomly divided into four subgroups, the model group (Model), quercetin group (Quercetin), MSCs group (MSCs), and pretreated MSCs with IronQ group (MSCs+IronQ). Neurological deficits were re-evaluated on day 3, and brain samples were collected for further analysis. TUNEL staining was performed to assess cell DNA damage, and the protein expression levels of inflammatory factors and the cGAS-STING signaling pathway were investigated and analyzed.
Results:
Pretreated MSCs with IronQ effectively mitigate neurological deficits and reduce neuronal inflammation by modulating the microglial polarization. Moreover, the pretreated MSCs with IronQ suppress the protein expression levels of the cGAS-STING signaling pathway.
Conclusion:
These findings suggest that pretreated MSCs with IronQ demonstrate a synergistic effect in alleviating neuroinflammation, thereby improving neurological function, which is achieved through the inhibition of the cGAS-STING signaling pathway.
Insights
Iron-quercetin complex pretreated mesenchymal stem cells (MSCs) effectively reduce neuroinflammation and improve neurological function after intracerebral hemorrhage (ICH) by inhibiting the cGAS-STING pathway.
Area of Science:
- Neuroscience
- Regenerative Medicine
- Biochemistry
Background:
- Intracerebral hemorrhage (ICH) leads to significant morbidity and mortality, with neuroinflammation being a key factor.
- Mesenchymal stem cells (MSCs) show therapeutic potential for brain diseases but their efficacy is limited by the inflammatory environment in ICH.
- The iron-quercetin complex (IronQ) enhances MSC survival and viability, offering a strategy to improve MSC-based therapies.
Purpose of the Study:
- To evaluate the therapeutic effects of MSCs pretreated with IronQ on neuroinflammation in an ICH mouse model.
- To elucidate the underlying mechanisms by which IronQ-pretreated MSCs modulate neuroinflammation and neurological function.
Main Methods:
- Intracerebral hemorrhage was induced in mice using collagenase I.
- Mice were treated with MSCs or MSCs pretreated with IronQ (MSCs+IronQ).
- Neurological deficits, cell DNA damage (TUNEL staining), inflammatory factors, and the cGAS-STING pathway were assessed.
Main Results:
- MSCs pretreated with IronQ significantly mitigated neurological deficits and reduced neuronal inflammation.
- IronQ-pretreated MSCs modulated microglial polarization, suppressing inflammatory responses.
- Protein expression of the cGAS-STING signaling pathway was suppressed by MSCs+IronQ treatment.
Conclusions:
- Pretreated MSCs with IronQ exhibit a synergistic effect in alleviating neuroinflammation and improving neurological function post-ICH.
- The therapeutic benefits are mediated through the inhibition of the cGAS-STING signaling pathway.
- This approach enhances MSC therapeutic potential for treating intracerebral hemorrhage.
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