Development of physiologically relevant skin organoids from human induced pluripotent stem cells
Open accessAbstract
The development of skin organs for studying developmental pathways, modeling diseases, or regenerative medicine purposes is a major endeavor in the field. Human induced pluripotent stem cells (hiPSCs) are successfully used to derive skin cells, but the field is still far from meeting the goal of creating skin containing appendages, such as hair follicles and sweat glands. Here, the goal is to generate skin organoids (SKOs) from human skin fibroblast or placental CD34+ cell-derived hiPSCs. With all three hiPSC lines, complex SKOs with stratified skin layers and pigmented hair follicles are generated with different efficacies. In addition, the hiPSC-derived SKOs develop sebaceous glands, touch-receptive Merkel cells, and more importantly eccrine sweat glands. Together, physiologically relevant skin organoids are developed by direct induction of embryoid body formation, along with simultaneous inactivation of transforming growth factor beta signaling, activation of fibroblast growth factor signaling, and inhibition of bone morphogenetic protein signaling pathways. The skin organoids created in this study can be used as valuable platforms for further research into human skin development, disease modeling, or reconstructive surgeries.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In SKO differentiation, modulation of TGFβ and FGF signaling pathways co-induces differentiation of epithelial and mesenchymal lineages, mimicking human fetal skin development.
“In SKO differentiation, for example, the modulation of the transforming growth factor beta (TGFβ) and fibroblast growth factor (FGF) signaling pathways co-induces the differentiation of epithelial and mesenchymal lineages, mimicking human fetal skin development [8, 9].”
From The empowering influence of air-liquid interface culture on skin organoid hair follicle development (2025) · cites this paper as [9]
An optimized SKO differentiation protocol using direct embryoid body formation from hiPSCs results in cystic SKOs that develop sensory neural networks, HFs, and sweat gland-like structures.
“Recently, an optimized SKO differentiation protocol was established by using direct embryoid body formation from hiPSCs as an immediate differentiation step, resulting in the formation of cystic SKOs that develop sensory neural networks, HFs, and sweat gland-like structures [9].”
From The empowering influence of air-liquid interface culture on skin organoid hair follicle development (2025) · cites this paper as [9]
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 [25]
There has been a complete absence of an endogenously differentiating vascularized, hair-bearing human skin equivalent that contains immune cell populations.
“While many attempts to generate complex 3D skin equivalents have achieved vascularization, hair follicle generation, and immune cell co‐cultures, there has been a complete absence of endogenously differentiating a vascularized, hair‐bearing human skin equivalent that contains immune cell populations.[ 21 , 22 , 23 , 24 , 25 , 26 , 27 ]”
From Coordinated Development of Immune Cell Populations in Vascularized Skin Organoids from Human Induced Pluripotent Stem Cells (2025) · cites this paper as [25]
Hair follicles in VSKOs are SOX2+, K14+, K15+, and K17+, as seen in the current SKO model.
“Figure 7c also shows that the hair follicles in VSKOs are SRY‐box transcription factor 2 (SOX2)+, K14+, cytokeratin 15 (K15)+, and K17+, as seen in the current SKO model.[ 25 , 26 ]”
From Coordinated Development of Immune Cell Populations in Vascularized Skin Organoids from Human Induced Pluripotent Stem Cells (2025) · cites this paper as [25]
Previous reports described the absence of immune and vascular components during hiPSC-derived SKO differentiation.
“Previous reports described the absence of immune and vascular components during hiPSC‐derived SKO differentiation.[ 25 , 26 , 33 ]”
From Coordinated Development of Immune Cell Populations in Vascularized Skin Organoids from Human Induced Pluripotent Stem Cells (2025) · cites this paper as [25]
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 [25]
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 [25]
Cites
Human organoids: model systems for human biology and medicine
Kim, J., Koo, B.-K., & Knoblich, J. A. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-0259-3 · Cited by 2,187 · see citing works
The immunological anatomy of the skin
Kabashima, K., Honda, T., Ginhoux, F., & Egawa, G. (2019) · Nature Reviews Immunology · doi:10.1038/s41577-018-0084-5 · Cited by 650 · see citing works
Hair-bearing human skin generated entirely from pluripotent stem cells
Lee, J., Rabbani, C. C., Gao, H., Steinhart, M. R., Woodruff, B. M., Pflum, Z. E., Kim, A., Heller, S., Liu, Y., Shipchandler, T. Z., et al. (2020) · Nature · doi:10.1038/s41586-020-2352-3 · Cited by 487 · see citing works
Sox2-positive dermal papilla cells specify hair follicle type in mammalian epidermis
Driskell, R. R., Giangreco, A., Jensen, K. B., Mulder, K. W., & Watt, F. M. (2009) · Development · doi:10.1242/dev.038620 · Cited by 331 · see citing works
Characterization of the epidermal-dermal junction in hiPSC-derived skin organoids
Ramovs, V., Janssen, H., Fuentes, I., Pitaval, A., Rachidi, W., Chuva de Sousa Lopes, S. M., Freund, C., Gidrol, X., Mummery, C. L., & Raymond, K. (2022) · Stem Cell Reports · doi:10.1016/j.stemcr.2022.04.008 · Cited by 44 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The empowering influence of air-liquid interface culture on skin organoid hair follicle development
Sun, J., Ahmed, I., Brown, J., Khosrotehrani, K., & Shafiee, A. (2025) · Burns & Trauma · doi:10.1093/burnst/tkae070 · Cited by 19 · see citing works
Self-citationMostina, M., Sun, J., Sim, S. L., Ahmed, I. A., Souza‐Fonesca‐Guimaraes, F., Wolvetang, E. J., Brown, J., Kumari, S., Khosrotehrani, K., & Shafiee, A. (2025) · Advanced Healthcare Materials · doi:10.1002/adhm.202502108 · Cited by 17 · see citing works
Self-citationDiversity of human skin three-dimensional organotypic cultures
Jia, Y. Y., & Atwood, S. X. (2024) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2024.102275 · Cited by 12 · see citing works
Kageyama, T., Anakama, R., Hamano, S., Tu, S., Migita, Y., Asaba, T., Nanmo, A., Ishikawa, K., Yan, L., Seo, J., et al. (2026) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.5c01780 · Cited by 6 · see citing works
- Authors
- Shafiee, A., Sun, J., Ahmed, I. A., Phua, F., Rossi, G. R., Lin, C., Souza‐Fonseca‐Guimaraes, F., Wolvetang, E. J., Brown, J., & Khosrotehrani, K.
- Affiliations
- Queensland Health (AU)
- The University of Queensland (AU)
- Frazer Institute Faculty of Medicine The University of Queensland Brisbane QLD 4102 Australia
- Corresponding author
- Shafiee, Abbas
- ORCID
- Venue
- Small
- Publisher
- Wiley
- Published
- 2023-12-03
- Volume
- 20
- Issue
- 16
- Pages
- e2304879-e2304879
- ISSN
- 1613-6810 (ISSN-L)
- 1613-6829
- OpenAlex
- W4389289068
- Cited by
- 54
- References
- 5
- Citations by year
- 2026: 18 · 2025: 23 · 2024: 13
- FWCI
- 4.81
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Small (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Metro North Hospital and Health Service
- National Health and Medical Research Council (GNT1140406)
- U.S. Department of Defense (#BC200025)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Health Sciences › Medicine › Urology › Hair Growth and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Skin and Cellular Biology Research
- Keywords
- skin organoids, human induced pluripotent stem cells, hair follicle, eccrine sweat glands, sebaceous glands, Merkel cells, embryoid body formation, TGF-beta inhibition, FGF signaling, BMP signaling inhibition, skin development, disease modeling, regenerative medicine, dermal fibroblasts
- MeSH terms
- Female, Humans, Organoids, Placenta, Pregnancy, Skin, Hair Follicle, Induced Pluripotent Stem Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
