Pretreated MSCs with IronQ Transplantation Attenuate Microglia Neuroinflammation via the cGAS-STING Signaling Pathway

Abstract

Guoqiang Yang,1– 3 Jiraporn Kantapan,3 Maryam Mazhar,4,5 Qiongdan Hu,1,5,6 Xue Bai,5,7 Yuanxia Zou,1,3 Honglian Wang,1 Sijin Yang,4,5 Li Wang,1,5 Nathupakorn Dechsupa3 1Research Center for Integrated Chinese and Western Medicine, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 2Acupuncture and Rehabilitation Department, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 3Molecular Imaging and Therapy Research Unit, Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand; 4National Traditional Chinese Medicine Clinical Research Base and Drug Research Center of the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 5Institute of Integrated Chinese and Western Medicine, Southwest Medical University, Luzhou, People’s Republic of China; 6Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand; 7Department of Neurology and National Traditional Chinese Medicine Clinical Research Base, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, People’s Republic of ChinaCorrespondence: Li Wang; Nathupakorn Dechsupa, Email [email protected]; [email protected]: 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.Keywords: mesenchymal stem cells, IronQ, intracerebral hemorrhage, cGAS/STING/NFκB, inflammatory response

Keywords

• mesenchymal stem cells
• ironq
• intracerebral hemorrhage
• cgas/sting/nfκb
• inflammatory response.