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.

We compare here the principal characteristics of over-the-counter moisturizers with physiologic lipid-based barrier repair therapy. Moisturizers are standard ancillary therapy for anti-inflammatory skin disorders, like atopic dermatitis (AD), and can attenuate the emergence of AD, the initial step in the “atopic march.” But not all moisturizers are beneficial; some can make skin function worse, and can even induce inflammation, possibly accounting for the frequent occurrence of “sensitive skin” in women. In contrast, physiologic lipid-based barrier repair therapy, if comprised of the 3 key stratum corneum lipids, in sufficient quantities and at an appropriate molar ratio, can correct the barrier abnormality and reduce inflammation in AD, and perhaps in other inflammatory dermatoses.

We compare here the principal characteristics of over-the-counter moisturizers with physiologic lipid-based barrier repair therapy. An extended literature revealed that moisturizers are considered standard ancillary therapy for anti-inflammatory skin disorders, like atopic dermatitis (AD). Additional studies have shown that physiologic lipid-based barrier repair therapy can comprise effective, stand-alone therapy for pediatric AD. Not all moisturizers are beneficial - some negatively impact skin function, and in doing so, they risk inducing or exacerbating inflammation in patients with AD. The frequent self-reported occurrences of ‘sensitive skin’ in atopics could reflect the potential toxicity of such formulations. A still unanswered question is whether improper formulations could also prove to be counterproductive in other types of sensitive skin, such as rosacea. In contrast, we show how physiologic lipid-based barrier repair therapy (BRT), if comprised of the three, key stratum corneum lipids in sufficient quantities and at an appropriate molar ratio, can correct the barrier abnormality thereby reducing inflammation in AD, and possibly in other inflammatory dermatoses, such as the ‘adult’ eczemas and possibly even psoriasis. We provide guidelines for the appropriate dispensation of moisturizers and physiologic lipid-based, barrier repair therapy for the treatment of AD. Both OTC (AtopalmÒ) and Rx (EpiCeramÒ) products are available in the USA with these characteristics.