Exosomes are nano-sized vesicles that serve as mediators for cell-to-cell communication. With their unique nucleic acids, proteins, and lipids cargo compositions that reflect the characteristics of producer cells, exosomes can be utilized as cell-free therapeutics. Among exosomes derived from various cellular origins, mesenchymal stem cell-derived exosomes (MSC-exosomes) have gained great attention due to their immunomodulatory and regenerative functions. Indeed, many studies have shown anti-inflammatory, anti-aging and wound healing effects of MSC-exosomes in various in vitro and in vivo models. In addition, recent advances in the field of exosome biology have enabled development of specific guidelines and quality control methods, which will ultimately lead to clinical application of exosomes. This review highlights recent studies that investigate therapeutic potential of MSC-exosomes and relevant mode of actions for skin diseases, as well as quality control measures required for development of exosome-derived therapeutics.
Recent studies have suggested that dietary factors, specifically glycaemic load, may be involved in the pathogenesis of acne. The aim of this study was to determine the clinical and histological effects on acne lesions of a low glycaemic load diet. A total of 32 patients with mild to moderate acne were randomly assigned to either a low glycaemic load diet or a control group diet, and completed a 10-week, parallel dietary intervention trial. Results indicate successful lowering of the glycaemic load. Subjects within the low glycaemic group demonstrated significant clinical improvement in the number of both non-inflammatory and inflammatory acne lesions. Histopathological examination of skin samples revealed several characteristics, including reduced size of sebaceous glands, decreased inflammation, and reduced expression of sterol regulatory element-binding protein-1, and interleukin-8 in the low glycaemic load group. A reduction in glycaemic load of the diet for 10 weeks resulted in improvements in acne.
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.
Acne vulgaris is a highly prevalent skin disorder characterized by hyperseborrhea, inflammation, and Propionibacterium acnes overgrowth. Only isotretinoin and hormonal therapy reduce sebum production. To identify a new drug candidate that modulates sebum, we examined the effects of EGCG, the major polyphenol in green tea, on human SEB-1 sebocytes and in patients with acne. In SEB-1 sebocytes, we found that EGCG reduced sebum by modulating the AMPK-SREBP-1 signaling pathway. EGCG also reduces inflammation by suppressing the NF-κB and AP-1 pathways. EGCG also induces cytotoxicity of SEB-1 sebocytes via apoptosis and decreases the viability of P. acnes, thus targeting almost all the pathogenic features of acne. Finally, and most importantly, EGCG significantly improved acne in an 8-week randomized, split-face, clinical trial, and was well tolerated. Our data provide a therapeutic rationale for the use of EGCG in acne.
SummaryThere are four central factors that contribute to acne physiopathology: the inflammatory response, colonization with Propionibacterium acnes, increased sebum production and hypercornification of the pilosebaceous duct. In addition, research in the areas of diet and nutrition, genetics and oxidative stress is also yielding some interesting insights into the development of acne. In this paper we review some of the most recent research and novel concepts revealed in this work, which has been published by researchers from diverse academic disciplines including dermatology, immunology, microbiology and endocrinology. We discuss the implications of their findings (particularly in terms of opportunities to develop new therapies), highlight interrelationships between these novel factors that could contribute to the pathology of acne, and indicate where gaps in our understanding still exist.Acne vulgaris is a near universal cutaneous inflammatory disease affecting more than 85% of adolescents worldwide.
1,2While not a fatal disease, acne can persist throughout life and leave permanent scarring on the face as a result. Four distinct processes are believed to play critical roles in the formation of acne lesions: alteration of keratinization processes, leading to comedo formation; follicular colonization by Propionibacterium acnes; increased sebum production and inflammatory mediators around pilosebaceous units. [3][4][5] Several medications that have been devised to target these pathogenic mechanisms have demonstrated modest efficacy, but their use is also accompanied by potentially serious side-effects.6,7The exact sequence of events and how they are interconnected is still unknown, due to the inherent complexity of this disease. Ongoing research is modifying the classical view of acne pathogenesis through identification of underlying mechanisms for previous theories and experimental findings. Recently, researchers from diverse academic disciplines including dermatology, immunology, microbiology and endocrinology have reported novel concepts for acne physiopathology by employing cutting-edge experimental methods and academic approaches.The four central factors that contribute to acne physiopathology are inflammation, colonization with P. acnes, increased sebum production and hypercornification of the pilosebaceous duct. Recent research suggests that these factors are much more interrelated than has been previously understood. Novel factors that could contribute to acne physiopathology include inflammasomes, T helper (Th)17 cell immunology, P. acnes sequence type and nutritional factors.In this article we review the most recent findings in acne physiopathology. We focus on specific issues associated with each of the four pathogenic factors, as well as some additional interesting research pathways, which may provide novel frameworks for improving our understanding of the disease pathogenesis and development of new medications. Finally, we provide a brief outlook of the prospects for this intriguing field of dermatolo...
This study was undertaken to evaluate the clinical efficacy, safety, and histological changes induced by dietary omega-3 fatty acid and γ-linoleic acid in acne vulgaris. A 10-week, randomised, controlled parallel dietary intervention study was performed in 45 participants with mild to moderate acne, which were allocated to either an omega-3 fatty acid group (2,000 mg of eicosapentaenoic acid and docosahexaenoic acid), a γ-linoleic acid group (borage oil containing 400 mg γ-linoleic acid), or a control group. After 10 weeks of omega-3 fatty acid or γ-linoleic acid supplementation, inflammatory and non-inflammatory acne lesions decreased significantly. Patient subjective assessment of improvement showed a similar result. Heamatoxylin & eosin staining of acne lesions demonstrated reductions in inflammation and immunohistochemical staining intensity for interleukin-8. No severe adverse effect was reported. This study shows for the first time that omega-3 fatty acid and γ-linoleic acid could be used as adjuvant treatments for acne patients.
This LED phototherapy was safe and effective for treating not only inflammatory but also noninflammatory acne lesions, with good compliance. The experimental results correlated well with clinical results, partly elucidating the related molecular mechanisms.
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