Mesenchymal stem cells transplantation combined with IronQ attenuates ICH-induced inflammation response via Mincle/Syk signaling pathway

Abstract: Background Cerebral edema, inflammation, and subsequent neurological defecit, are the common consequences of intracerebral hemorrhage (ICH). Mesenchymal stem cells (MSCs) transplantation had been used as a neuroprotective therapy in nervous system diseases because of its anti-inflammatory effect. However, the survival, viability, and efficacy of MSCs are limited due to the severe inflammatory response after ICH. Therefore, ways to improve the survival and viability of MSCs will provide a hopeful therapeutic efficacy for ICH. Notably, the metal-quercetin complex via coordination chemistry has been verified positively and studied extensively for biomedical applications, including growth-promoting and imaging probes. Previous studies have shown that the iron-quercetin complex (IronQ) has excellent dual functions with a stimulating agent of cell growth and an imaging probe for magnetic resonance imaging (MRI). Therefore, we hypothesized that IronQ could improve the survival and viability of MSCs, displaying the anti-inflammation function in the treatment of ICH, while also label MSCs for their tracking by MRI. This study was designed to investigate the effects of the combined treatment of MSCs with IronQ on inflammation and elucidate their underlying mechanisms. Methods A collagenase I-induced ICH mice model was extablished, which were randomly divided into model group (Model), quercetin gavage group (Quercetin), MSCs transplantation group (MSCs), and MSCs transplantation combined with IronQ group (MSCs + IronQ). Then the neurological deficits score, brain water content (BWC), and the protein expression levels of IL-6, TNF-α, NeuN, MBP, and GFAP were investigated. We measured the protein expression levels of Mincle and its downstream targets. Furthermore, the lipopolysaccharide (LPS)-induced BV2 cells was used to investigate the neuroprotection of conditioned medium of MSCs co-cultured IronQ in vitro. Results We found that the combined treatment improves the inflammation-induced neurological function and BWC by inhibiting the Mincle/Syk signaling pathway in vivo. The conditioned medium of MSCs co-cultured with IronQ decreased inflammation, the protein expression levels of Mincle, and its downstream targets in LPS-induced BV2 cell line. Conclusions These data suggested that the combined treatment plays a synergistic role in ameliorating the consequences of ICH, including neurologic deficits, brain edema, and inflammatory response through the downregulation of the Mincle/syk signaling pathway.