Wnt-activating human skin organoid model of atopic dermatitis induced by Staphylococcus aureus and its protective effects by Cutibacterium acnes
Open accessAbstract
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.
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When human SKOs were planarized and transferred to ALI at Day 85 to 100, maturation of SKO epidermal layers was enhanced, with increased stratum corneum formation and expression of loricrin and filaggrin.
“Similarly, when human SKOs were planarized and transferred to an ALI at Day 85 to 100 of culture, the maturation of the SKO epidermal layers was enhanced, as indicated by significantly increased stratum corneum formation and expression of mature keratinocyte markers, loricrin, and filaggrin [16].”
From The empowering influence of air-liquid interface culture on skin organoid hair follicle development (2025) · cites this paper as [16]
The Results (Air-liquid interface (ALI)-skin organoids) say ALI culture began around days 85–100 and improved epidermal maturation. They attribute the significant increases in cornified stratum formation and loricrin and filaggrin expression specifically to a subsequent dry-culture phase, rather than to transfer to ALI alone. (LLM, conf=0.86)
Experimental — accuracy not yet measuredPrevious studies have shown that skin organoids can generate stratified epidermal and dermal compartments, but they generally fail to establish vascular structures, a defining feature of native human skin.
“Previous studies have shown that skin organoids can generate stratified epidermal and dermal compartments, but they generally fail to establish vascular structures, a defining feature of native human skin 13,16 .”
From Vascularized human skin assembloids model compartmental skin organization and immune responsiveness in vitro (2026) · cites this paper as [13]
The Discussion reports that this paper’s ALI-skin organoids have a dermis beneath a stratified epidermis, and the Limitations of the study section explicitly says the system lacks vasculature (page numbers unavailable). Those passages support the claim for this model, but do not establish that skin organoids generally fail to form vascular structures. (LLM, conf=0.86)
Experimental — accuracy not yet measuredPSOs are already being adopted for various applications including disease modeling and regenerative therapy.
“Despite their recent discovery, PSOs are already being adopted for various applications including disease modeling and regenerative therapy [5,7–9], yet several considerations remain, such as their limited maturation and efficiency, and non-anatomical organization of dermal and epidermal compartments.”
From Efficient Generation of Skin Organoids from Pluripotent Cells via Defined Extracellular Matrix Cues and Morphogen Gradients in a Spindle‐Shaped Microfluidic Device (2024) · cites this paper as [5]
The Introduction describes pluripotent stem cell-derived skin organoids as a platform for investigating disease and regeneration, and the Discussion reports their use to model atopic dermatitis. It does not establish that they are already being adopted for regenerative therapy; investigating regeneration is not the same as therapeutic use. The indexed passages provide no page numbers. (LLM, conf=0.86)
Experimental — accuracy not yet measuredSkin organoids with inside-out anatomy have to be precisely incised and/or manually inverted to generate functional grafts and models.
“Moreover, skin organoids with inside-out anatomy have to be precisely incised and/or manually inverted to generate functional grafts and models [3,5].”
From Efficient Generation of Skin Organoids from Pluripotent Cells via Defined Extracellular Matrix Cues and Morphogen Gradients in a Spindle‐Shaped Microfluidic Device (2024) · cites this paper as [5]
The Introduction describes enclosed skin organoids with inside-out anatomy. In Results > Air-liquid interface (ALI)-skin organoids (page unavailable), the authors report dissecting organoids into four portions and placing them dermis-down to expose the epidermis, producing a skin model. The paper does not establish that precise incision or manual inversion is necessary for functional grafts, and it does not describe generating grafts. (LLM, conf=0.86)
Experimental — accuracy not yet measuredPrevious studies reported enhanced maturation, development, and function of human organoids in the laboratory.
“These previous studies have reported enhanced maturation, development, and function of human organoids in the laboratory [16, 28].”
From The empowering influence of air-liquid interface culture on skin organoid hair follicle development (2025) · cites this paper as [16]
Skin organoids derived from hiPSCs recapitulate epidermal and dermal differentiation and generate appendages such as hair follicles, melanocytes and neurons.
“Skin organoids (SkOs) derived from hiPSCs recapitulate epidermal and dermal differentiation and generate appendages such as hair follicles, melanocytes and neurons 13,14 .”
From Vascularized human skin assembloids model compartmental skin organization and immune responsiveness in vitro (2026) · cites this paper as [13]
hiPSC-derived skin organoids have hair follicles, pigmentation, dermal stratification, appendage patterning, and innervation.
“Recent advances in human induced pluripotent stem cell (hiPSC) technology have enabled the generation of skin organoids (SKO) with hair follicles, pigmentation, dermal stratification, appendage patterning, and innervation.[ 25 , 26 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ]”
From Coordinated Development of Immune Cell Populations in Vascularized Skin Organoids from Human Induced Pluripotent Stem Cells (2025) · cites this paper as [28]
Previous human SKO models were devoid of vascularization and immune cells.
“Previous human SKO models were devoid of vascularization and immune cells.[ 25 , 26 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 59 ]”
From Coordinated Development of Immune Cell Populations in Vascularized Skin Organoids from Human Induced Pluripotent Stem Cells (2025) · cites this paper as [28]
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- Authors
- Jung, S.-Y., You, H. J., Kim, M.-J., Ko, G., Lee, S., & Kang, K.-S.
- Affiliations
- Seoul National University (KR)
- Kangstem Biotech Co., Ltd. (South Korea) (KR)
- Corresponding author
- Kang, Kyung-Sun
- Venue
- iScience
- Publisher
- Elsevier BV
- Published
- 2022-10
- Volume
- 25
- Issue
- 10
- Pages
- 105150
- ISSN
- 2589-0042 (ISSN-L)
- PMC
- PMC9526179
- OpenAlex
- W4296051926
- Cited by
- 63
- References
- 33
- Citations by year
- 2026: 18 · 2025: 23 · 2024: 17 · 2023: 5
- FWCI
- 11.00
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- iScience (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Research Foundation of Korea
- Ministry of Science, ICT and Future Planning (2020R1A4A4078907)
- Topics
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advancements in Transdermal Drug Delivery
- Keywords
- atopic dermatitis, skin organoids, Wnt signaling, Staphylococcus aureus, Propionibacterium acnes, air-liquid interface culture, skin barrier disruption, inflammatory cytokines, Staphylococcus aureus colonization, organoid morphology
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