Wnt-activating human skin organoid model of atopic dermatitis induced by Staphylococcus aureus and its protective effects by Cutibacterium acnes


A recently developed human PSC-derived skin organoid model has opened up new avenues for studying skin development, diseases, and regeneration. The current model has limitations since the generated organoids are enclosed, circular aggregates with an inside-out morphology with unintended off-target development of cartilage. Here, we first demonstrated that Wnt signaling activation resulted in larger organoids without off-target cartilage. We optimized further using an air-liquid interface (ALI) culture method to recapitulate structural features representative of human skin tissue. Finally, we used the ALI-skin organoid platform to model atopic dermatitis by Staphylococcus aureus (SA) colonization and infection. SA infection led to a disrupted skin barrier and increased production of epidermal- and dermal-derived inflammatory cytokines. Additionally, we found that pre-treatment with Cutibacterium acnes had a protective effect on SA-infected organoids. Thus, this ALI-skin organoid platform may be a useful tool for modeling human skin diseases and evaluating the efficacy of novel therapeutics. © 2022 The Author(s).

Authors Jung SY, You HJ, Kim MJ, Ko G, Lee S, Kang KS
Journal iScience
Publication Date 2022 Oct 21;25(10):105150
PubMed 36193049
PubMed Central PMC9526179
DOI 10.1016/j.isci.2022.105150

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