iPSC‐Derived MSC Secretome as a Protective and Restorative Modality for Atopic Dermatitis

Background Atopic dermatitis (AD) is a chronic inflammatory skin disease that significantly impacts quality of life. Reducing inflammation and restoring the skin barrier are key to its management. Objective This study aimed to investigate the protective and therapeutic effects of secretory substances from induced pluripotent stem cell (iPSC)‐derived mesenchymal stem cells (iMSCs) in AD. Methods The protective effects of iMSC secretome pretreatment were evaluated in HaCaT cells by assessing cell viability, AD biomarker expression, and cell migration. Therapeutic efficacy was examined in a 1‐chloro‐2,4‐dinitrobenzene (DNCB)‐induced AD mouse model through clinical, histological, and immunological assessments. Proteomic analyses were performed to relevant biological processes. Results iMSC secretome significantly reduced AD‐induced cell death and AD biomarker expressions in vitro ( p   < 0.05), with 200 μg/mL iMSC secretome promoting cell migration. In vivo, high dose (20 mg/mL) iMSC secretome alleviate clinical indicators compared to the vehicle group ( p   < 0.05). Serum immunoglobulin (Ig) E, interleukin (IL)‐4, IL‐31, and IL‐6 levels, along with the expression of AD biomarkers in skin, were significantly decreased ( p   < 0.05). Proteomic analyses revealed upregulation of genes involved in the regulation of immune responses and the restoration of skin barrier. Conclusion iMSC secretome demonstrates significant anti‐inflammatory and regenerative effects, making it a promising therapeutic option for AD.