Wnt-activating human skin organoid model of atopic dermatitis induced by Staphylococcus aureus and its protective effects by Cutibacterium acnes
Song-yi Jung,
Hyun Ju You,
Min-Ji Kim,
GwangPyo Ko,
Seunghee Lee,
Kyung-Sun Kang
Affiliations
Song-yi Jung
Adult Stem Cell Research Center and Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul 08826, Republic of Korea
Hyun Ju You
Department of Environmental Health Sciences, Graduate School of Public Health, Seoul National University, Seoul 08826, Republic of Korea; KoBioLabs, Inc., Seoul 08826, Republic of Korea
Min-Ji Kim
Adult Stem Cell Research Center and Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul 08826, Republic of Korea
GwangPyo Ko
Department of Environmental Health Sciences, Graduate School of Public Health, Seoul National University, Seoul 08826, Republic of Korea; Bio-MAX/N-Bio, Seoul National University, Seoul 08826, Republic of Korea; KoBioLabs, Inc., Seoul 08826, Republic of Korea
Seunghee Lee
Stem Cell and Regenerative Bioengineering Institute, Global R&D Center, Kangstem Biotech Co. Ltd., Seoul 08590, Republic of Korea
Kyung-Sun Kang
Adult Stem Cell Research Center and Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul 08826, Republic of Korea; Corresponding author
Summary: 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.
