Quercetin pretreated umbilical cord mesenchymal stem cells alleviate inflammatory bowel disease via IL-10/Janus kinase 2/STAT3 signaling

Abstract

BACKGROUND Inflammatory bowel disease (IBD) is a chronic, progressive inflammatory condition of the intestine. Mesenchymal stem cell (MSC) therapy for IBD has made significant progress in recent years. To better exploit the therapeutic potential of MSCs, pretreatment strategies are employed to enhance their therapeutic capabilities. As a compound with diverse pharmacological effects, quercetin (QUR) is applied to pretreat human umbilical cord-derived MSCs (hUCMSCs) in this study, thereby augmenting their immunotherapeutic potential. AIM To evaluate the therapeutic efficacy of QUR-pretreated hUCMSCs. METHODS We induced colitis in a mouse model using a 2,4,6-trinitrobenzenesulfonic acid solution. Intraperitoneal injection of QUR-pretreated hUCMSCs significantly improved clinical and pathological manifestations of colitis compared to the model group. Interestingly, the therapeutic effect was superior to that of untreated hUCMSCs. Mice exhibited significantly reduced weight loss, diminished infiltration of inflammatory cells observed in hematoxylin and eosin staining, improved Disease Activity Index and Histological Activity Index scores. Furthermore, colonic tissue analysis revealed a significant upregulation of the anti-inflammatory cytokine interleukin 10 (IL-10), accompanied by a downregulation of the pro-inflammatory cytokine IL-6. Further tests also suggested that QUR pretreatment led to inhibition of Janus kinase/signal transducer and activator of transcription (STAT) phosphorylation. RESULTS Our study demonstrated that QUR pretreatment of hUCMSCs significantly enhanced their immune-regulatory capacity. This approach effectively mitigated colonic inflammation in a mouse colitis model by modulating the IL-10/Janus kinase/STAT signaling pathway. CONCLUSION These findings suggest that QUR pretreatment acts synergistically to augment the inherent anti-inflammatory and immune-regulatory properties of hUCMSCs, resulting in enhanced therapeutic efficacy for IBD treatment.