1090 Extracellular vesicles from IFN-gamma-primed induced mesenchymal stem cells improve atopic dermatitis in mice

Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by immune dysregulation, pruritus, and abnormal epidermal barrier function. Compared with conventional mesenchymal stem cell (MSC), induced pluripotent stem cell (iPSC)-derived mesenchymal stem cell (iMSC) is recognized as a unique source for producing extracellular vesicles (EVs) because it can be obtained in a scalable manner with an enhanced homogeneity. In this study, we investigated whether, EVs from IFN-γ stimulated of iMSCs have immune-regulatory, anti-inflammatory, and tissue-repairing potential in a mice model of AD. After DNCB was applied to the dorsal skin of NC/Nga mice for three weeks, AD symptoms were assessed. Then mice were treated with the IFN-γ-iMSC-EVs or a JAK inhibitor (Baricitinib) for four weeks. AD-like symptoms were demonstrated in the DNCB application mice, such as increased dermatitis score, scratching number, serum IgE level, epidermal thickness, and immune cell infiltration. Also, IFN-γ-iMSC-EVs decreased the expression of IL-4Rα, IL-13Rα1, TSLP, and their corresponding intracellular signaling molecules activated in AD-like mice. Furthermore, IFN-γ-iMSC-EVs decreased atopic dermatitis score, which was supported by reduced inflammatory cell infiltration and mast cells in AD skin . Impaired skin barrier, as evidenced by upregulation of keratin, filaggrin, and ceramide synthase, was also observed in AD mice that received IFN-γ-iMSC-EVs. The results of our study may contribute to developing novel cell-free therapeutic strategies for AD. IFN-γ-iMSC-EVs is currently undergoing phase 1 clinical trials in patients with atopic dermatitis.