Skin organoids: a new human model for developmental and translational research
Open accessAbstract
Culturing skin cells outside of the body has been a cornerstone of dermatological investigation for many years; however, human skin equivalent systems typically lack the full complexity of native skin. Notably, skin appendages, such as hair follicles and sweat glands, remain a challenge to generate or maintain in cell cultures and reconstruct in damaged skin. Recent work from our lab has demonstrated methods for generating appendage‐bearing skin tissue—known as skin organoids—from pluripotent stem cells. Here, we will summarize this work and other related works, and then discuss the potential future applications of skin organoids in dermatological research.
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Hair placode epithelium invaginates into the dermis and signals surrounding mesenchymal cells to cluster and form the early dermal papilla.
“The hair placode epithelium invaginates into the dermis while signaling to surrounding mesenchymal cells to cluster and form the early dermal papilla.”
From The empowering influence of air-liquid interface culture on skin organoid hair follicle development (2025) · cites this paper as [10]
In “The Challenge of Growing Skin Appendages in a Dish” (page unavailable), the paper describes chemical cues exchanged between the epidermis and dermis during development and discusses the establishment of hair placodes. It does not say that placode epithelium invaginates into the dermis or signals mesenchymal cells to cluster into an early dermal papilla. (LLM, conf=0.83)
Experimental — accuracy not yet measuredFurther crosstalk between epithelium and early dermal papilla drives additional invagination and maturation, leading to a mature HF with sebaceous glands, inner and outer root sheath regions, and a hair shaft.
“Further crosstalk between the epithelium and the early dermal papilla drives additional invagination and maturation, eventually leading to the development of a mature HF with sebaceous glands, inner and outer root sheath regions, and a hair shaft [7, 10].”
From The empowering influence of air-liquid interface culture on skin organoid hair follicle development (2025) · cites this paper as [10]
In “The Challenge of Growing Skin Appendages in a Dish” (page unavailable), the paper says the epidermis and dermis exchange cues during development and that skin organoids produce hair follicles. It does not describe crosstalk specifically with an early dermal papilla driving further invagination, or identify sebaceous glands, root sheaths, and a hair shaft as the resulting structures. (LLM, conf=0.83)
Experimental — accuracy not yet measuredEpithelial-mesenchymal crosstalk is necessary to induce formation of complex skin structures, in particular the pilosebaceous apparatus.
“The co-induction and development of these populations is a major improvement to previous skin models, as it allows for epithelial-mesenchymal crosstalk, which is necessary to induce the formation of complex skin structures, in particular the pilosebaceous apparatus [10].”
From The empowering influence of air-liquid interface culture on skin organoid hair follicle development (2025) · cites this paper as [10]
In “The Challenge of Growing Skin Appendages in a Dish” (page unavailable), the paper describes cues exchanged between epidermis and dermis during skin development and reports that co-developed epithelial and mesenchymal cells produce hair follicles. This supports a role for crosstalk in appendage formation, but the passages do not establish that crosstalk is strictly necessary or specifically address formation of the entire pilosebaceous apparatus. (LLM, conf=0.82)
Experimental — accuracy not yet measuredThe physiological relevance of hiPSC-derived SKOs remains limited by the absence of vascular and immune components, as SKOs are derived from differentiation of the surface ectoderm.
“Despite their experimental advantages over existing skin equivalents, the physiological relevance of hiPSC‐derived SKOs remains limited by the absence of vascular and immune components, as SKOs are derived from differentiation of the surface ectoderm.[ 36 , 37 , 38 ]”
From Coordinated Development of Immune Cell Populations in Vascularized Skin Organoids from Human Induced Pluripotent Stem Cells (2025) · cites this paper as [36]
The section “Increasing Complexity: Skin Organoids with Vasculature, Immune Cells, and Sweat Glands” says skin organoids lack endothelial cells, pericytes, and immune cells, supporting the stated limitation. But “The Challenge of Growing Skin Appendages in a Dish” says the organoids are generated by co-inducing surface ectoderm and cranial neural crest cells, not by differentiating surface ectoderm alone. The proposed explanation for the missing components is therefore not supported as stated. No page numbers are available in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredAlthough macrophage co-culture with SKOs has been reported, a physiologically relevant vascularized hiPSC-derived SKO has yet to be achieved.
“Although macrophage co‐culture with SKOs has been reported,[ 35 ] a physiologically relevant vascularized hiPSC‐derived SKO has yet to be achieved.[ 36 , 37 , 38 ]”
From Coordinated Development of Immune Cell Populations in Vascularized Skin Organoids from Human Induced Pluripotent Stem Cells (2025) · cites this paper as [36]
Currently, SKOs lack vasculature and immune cells in a physiologically relevant context.
“Currently, SKOs lack vasculature and immune cells in a physiologically relevant context.[ 25 , 35 , 36 , 37 , 38 ]”
From Coordinated Development of Immune Cell Populations in Vascularized Skin Organoids from Human Induced Pluripotent Stem Cells (2025) · cites this paper as [36]
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- Authors
- Lee, J., & Koehler, K. R.
- Affiliations
- Boston Children's Hospital (US)
- Corresponding author
- Koehler, Karl R.
- Venue
- Experimental Dermatology
- Publisher
- Wiley
- Published
- 2021-02-18
- Volume
- 30
- Issue
- 4
- Pages
- 613-620
- ISSN
- 0906-6705 (ISSN-L)
- 1600-0625
- PMC
- PMC8265774
- OpenAlex
- W3124575106
- Cited by
- 85
- References
- 83
- Citations by year
- 2026: 13 · 2025: 15 · 2024: 22 · 2023: 9 · 2022: 17 · 2021: 8
- FWCI
- 15.65
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Experimental Dermatology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR075018‐01)
- Topics
- Health Sciences › Medicine › Urology › Hair Growth and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Skin and Cellular Biology Research
- Keywords
- skin organoids, skin appendages, hair follicle, sweat glands, pluripotent stem cells, skin regeneration
- MeSH terms
- Cell Differentiation, Humans, Organoids, Regeneration, Skin, Cell Culture Techniques, Translational Research, Biomedical
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