Extracellular Vesicles from miR-146a Overexpressing Mesenchymal Stem Cells Attenuate Imiquimod-Induced Psoriasis by Regulating Cytokine Expression

Background: Psoriasis is a chronic inflammatory skin disorder characterized by elevated levels of proinflammatory cytokines. Mesenchymal stem cells (MSCs) have demonstrated therapeutic potential, yet the specific mechanisms involved are not fully understood. In this study, we investigated the effectiveness of extracellular vesicles (EVs) derived from MSCs that were genetically modified to overexpress miR-146a, in a mouse model of psoriasis. Methods: To enhance miR-146a expression, MSCs were transfected, and their EVs were subsequently purified. Thirty mice were randomly assigned to three groups and induced with imiquimod cream to develop psoriasis-like skin lesions. The treatment groups included: (1) a control group administered PBS, (2) a group treated with EVs containing a control miRNA (miR-control EVs), and (3) a group receiving EVs enriched with miR-146a (miR-146a-EVs). EVs were administered intravenously and lesions were evaluated. Following intravenous administration of EVs, the severity of skin lesions was assessed. Concentrations of key cytokines, including IFN-gamma, IL-17, TNF-alpha, IL-23, IL-6, IL-1(3, TGF-(3, IL-10, and IL-4, were quantified in both spleen and skin tissue lysates using ELISA and qRT-PCR techniques. Results: The experimental findings demonstrated that the administration of miR-146a-enriched EVs led to a significant improvement in clinical symptoms. There were substantial reductions observed in combined erythema, scaling, and skin thickness measurements compared to untreated controls. Additionally, levels of proinflammatory cytokines IFN-gamma, IL-17, TNF-alpha, IL-23, IL-6, and IL-1(3 were significantly downregulated in the miR-146a-EV group, while anti-inflammatory TGF-(3, IL-10 and IL-4 were upregulated. The same results were obtained in the spleens of mice. Conclusion: EVs derived from miR-146a-modified MSCs effectively reduced psoriasis-like inflammation by modulating cytokine expression. This novel cell-free therapy holds promise for the treatment of psoriasis.