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

Cells

Gyeong-Hun Park¹  DebraA. Crumrine²  JoanS. Wakefield²  PeterM. Elias²  JasonM. Meyer²  Sungeun Kim³  Yerin Lee³  Bogyeong Kim³  Kyungho Park³  Kyong-Oh Shin³  Hyun-keun Kim⁴  Jihye Lim⁴  ByongSeung Cho⁴  DaeHyun Ha⁴  YongWeon Yi⁴  JinOck Kim⁴  Sejeong Park⁴  JunHo Lee⁴  HyuckHoon Kwon⁵  Joon Lee⁶ 

[1] Department of Dermatology, Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong-si, Gyeonggi-do 431-060, Korea;Department of Dermatology, University of California, NCIRE, and Veterans Affairs Medical Center, San Francisco, CA 94121, USA;Department of Food Science and Nutrition, Convergence Program of Material Science for Medicine and Pharaceutics, Hallym University, Chuncheon 24252, Korea;ExoCoBio Exosome Institute (EEI), ExoCoBio Inc., Seoul 08594, Korea;Oaro Dermatology Clinic, Seoul 13620, Korea;School of Chemical and Biological Engineering, Seoul National University, Seoul 151-744, Korea;

关键词: asc-exosomes;    anti-inflammation;    atopic dermatitis;    restoration;    skin barrier;    lamella body;    ceramides;   

DOI  :  10.3390/cells9030680

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown