Exosomes derived from mesenchymal Stem cells alleviate atopic dermatitis by suppressing inflammation and improving skin barrier function

Abstract

Background & Aim Introduction Atopic dermatitis (AD) is a chronic, relapsing, and highly pruritic inflammatory skin disease affecting up to 20% of children and 1% of adults worldwide. Current evidence suggests that both impairment of epidermal barrier function and T helper 2 cell-mediated inflammatory pathway contribute to the pathogenesis of AD. Exosomes are nano-sized membrane-bound vesicles (30 – 200 nm) constantly released by almost all cells. The ability of exosomes to travel between cells and deliver genetic materials, such as microRNAs and proteins, makes them an appealing cell-free therapy option to treat multiple diseases by overcoming many drawbacks of cell-based therapy. In particular, exosomes derived from mesenchymal stem cells (MSCs) have been shown to facilitate tissue repair and regeneration, and reduce inflammation. Objective Here, we for the first time investigated whether human adipose tissue-derived mesenchymal stem cell-derived exosomes (ASC-exosomes) can ameliorate AD. Methods, Results & Conclusion Materials and Methods Human ASC-exosomes were isolated from the serum-free conditioned media by sequential filtration method and characterized as recommended by the International Society for Extracellular Vesicles (ISEV). AD-like skin lesions were induced in mice by treatment with a house dust mite antigen or a chemical irritant. Results When injected either intravenously (IV) or subcutaneously (SC) into murine model of AD, ASC-exosomes were found to significantly attenuate AD-like symptoms, such as skin lesion severity, serum IgE levels, and infiltrated mast cells. It was also found that ASC-exosomes significantly decreased mRNA levels of various inflammatory cytokines, such as interleukin (IL)-4, IL-23, IL31, and tumor necrosis factor-α (TNF-α) in AD skin lesions. Furthermore, ASC-exosomes led to the improvement of skin barrier function as evidenced by enhanced skin hydration and reduced trans-epidermal water loss (TEWL) in skin lesions. Conclusions Taken together, our data suggests that ASC-exosomes could be a novel promising cell-free therapeutic modality for AD treatment.