Exosomes from Human Adipose Tissue-Derived Mesenchymal Stem Cells Promote Epidermal Barrier Repair by Inducing de Novo Synthesis of Ceramides in Atopic Dermatitis

• Published in: Cells (Basel, Switzerland) Vol. 9; no. 3; p. 680
• Main Authors: Shin, Kyong-Oh, Ha, Dae Hyun, Kim, Jin Ock, Crumrine, Debra A, Meyer, Jason M, Wakefield, Joan S, Lee, Yerin, Kim, Bogyeong, Kim, Sungeun, Kim, Hyun-Keun, Lee, Joon, Kwon, Hyuck Hoon, Park, Gyeong-Hun, Lee, Jun Ho, Lim, Jihye, Park, Sejeong, Elias, Peter M, Park, Kyungho, Yi, Yong Weon, Cho, Byong Seung
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 10.03.2020; MDPI
• Subjects: Adipose tissue; Adipose Tissue - metabolism; Animals; anti-inflammation; asc-exosomes; Atopic dermatitis; Body fat; Cell cycle; ceramides; Ceramides - biosynthesis; Ceramides - metabolism; Dermatitis; Dermatitis, Atopic - drug therapy; Dermatitis, Atopic - pathology; Epidermis - metabolism; Exosomes; Exosomes - metabolism; Female; Humans; Hypotheses; Inflammation; Interleukin 13; Interleukin 17; Interleukin 4; Interleukin 5; lamella body; Lipid metabolism; Membranes; Mesenchymal stem cells; Mesenchymal Stem Cells - metabolism; Mice; MicroRNAs; Microscopy; Nanoparticles; Oxazolone; Pathogenesis; Proteins; restoration; Ribonucleic acid; RNA; Sequence analysis; skin barrier; Skin diseases; Skin lesions; Stem cells; Stratum corneum; Thymic stromal lymphopoietin; Tumor necrosis factor-α; γ-Interferon; United States > US; skin barrier; ASC-exosomes; atopic dermatitis; anti-inflammation; lamella body; ceramides; restoration
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells9030680

Atopic dermatitis (AD) is a multifactorial, heterogeneous disease associated with epidermal barrier disruption and intense systemic inflammation. Previously, we showed that exosomes derived from human adipose tissue-derived mesenchymal stem cells (ASC-exosomes) attenuate AD-like symptoms by reducing multiple inflammatory cytokine levels. Here, we investigated ASC-exosomes' effects on skin barrier restoration by analyzing protein and lipid contents. We found that subcutaneous injection of ASC-exosomes in an oxazolone-induced dermatitis model remarkably reduced trans-epidermal water loss, while enhancing stratum corneum (SC) hydration and markedly decreasing the levels of inflammatory cytokines such as IL-4, IL-5, IL-13, TNF-α, IFN-γ, IL-17, and TSLP, all in a dose-dependent manner. Interestingly, ASC-exosomes induced the production of ceramides and dihydroceramides. Electron microscopic analysis revealed enhanced epidermal lamellar bodies and formation of lamellar layer at the interface of the SC and stratum granulosum with ASC-exosomes treatment. Deep RNA sequencing analysis of skin lesions demonstrated that ASC-exosomes restores the expression of genes involved in skin barrier, lipid metabolism, cell cycle, and inflammatory response in the diseased area. Collectively, our results suggest that ASC-exosomes effectively restore epidermal barrier functions in AD by facilitating the de novo synthesis of ceramides, resulting in a promising cell-free therapeutic option for treating AD.