Generating Skin‐Derived Precursor‐Like Cells From Human‐Induced Pluripotent Stem Cell‐Derived Skin Organoids
Open accessAbstract
Skin‐derived precursor (SKPs) cells are multipotent stem cells found in the dermis that contribute to wound healing and induce hair follicle neogenesis when transplanted. The clinical application of adult human SKPs, however, is hindered by their loss of potency after in vitro expansion. To overcome this challenge, we aimed to isolate SKPs from human‐induced pluripotent stem cell‐derived skin organoids (SKOs), to enable mass production of these cells for therapeutics. We developed a protocol to isolate skin‐derived precursor‐like cells (SKP‐like cells) from human SKOs. SKP‐like cells derived from SKOs exhibited characteristic spheroid morphology and were capable of self‐renewal in defined SKP growth medium. Immunofluorescence analysis confirmed the expression of key markers, including SOX2, fibronectin and S100β, within the SKP‐like cells. The findings of this pilot study shed light on the potential of SKO‐derived SKP‐like cells for future hair regenerative applications. Furthermore, this research highlights the application of human SKOs as a valuable source for isolating progenitor cells, aiming to advance hair regeneration and restore skin function.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
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 [34]
Figure 1 (Conclusions & Future Perspectives; page not provided) shows hiPSC-derived skin organoids developing hair placodes and hair follicles, supporting the hair-follicle portion of the claim. The copy does not establish pigmentation, dermal stratification, broader appendage patterning, or innervation; searches for those features found no supporting passage. (LLM, conf=0.87)
Experimental — accuracy not yet measuredPrevious 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 [34]
The Conclusions & Future Perspectives section says that current skin substitutes lack the complexity of human skin, but does not say that previous SKO models lacked vascularization or immune cells. The Results describe SKO dermis and hair follicles; searches for vascularization, vasculature, blood vessels, and immune cells found no passage addressing the claimed absence. (LLM, conf=0.75)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
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 · cited 2× · see citing works
“The SKOs recapitulate early skin development and have a structural resemblance to the human foetal organ [21].”
Review of hair follicle dermal cells
Yang, C.-C., & Cotsarelis, G. (2010) · Journal of Dermatological Science · doi:10.1016/j.jdermsci.2009.11.005 · Cited by 418 · 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
Flagged first, then by citations
Research works printed but not linked: 24
- C. M. Abreu, L. Gasperini, and A. P. Marques, "Biofabrication Tech- nologies in Hair Neoformation," in Hair Follicle Regeneration, eds. F. Jimenez and C. Higgins (Cham: Springer International Publishing, 2022), 255-274.
- C. M. Abreu and A. P. Marques, "Recreation of a Hair Follicle Re- generative Microenvironment: Successes and Pitfalls," Bioengineering & Translational Medicine 7, no. 1 (2022): e10235.
- A. R. Castro and E. Logarinho, "Tissue Engineering Strategies for Human Hair Follicle Regeneration: How Far From a Hairy Goal?," Stem Cells Translational Medicine 9, no. 3 (2019): 342-350.
- J. Biernaskie, M. Paris, O. Morozova, et al., "SKPs Derive From Hair Follicle Precursors and Exhibit Properties of Adult Dermal Stem Cells," Cell Stem Cell 5, no. 6 (2009): 610-623.
- J. M. D. Legrand, E. Roy, J. J. Ellis, M. Francois, A. J. Brooks, and K. Khosrotehrani, "STAT5 Activation in the Dermal Papilla Is Important for Hair Follicle Growth Phase Induction," Journal of Investigative Der- matology 136, no. 9 (2016): 1781-1791.
- L. Guo, X. Wang, J. Yuan, et al., "TSA Restores Hair Follicle-Inductive Capacity of Skin-Derived Precursors," Scientific Reports 9, no. 1 (2019): 2867.
- R. Dai, W. Hua, H. Xie, W. Chen, L. Xiong, and L. Li, "The Human Skin- Derived Precursors for Regenerative Medicine: Current State, Challenges, and Perspectives," Stem Cells International 2018 (2018): 8637812.
- M. Bertolini, I. Piccini, and K. J. McElwee, "In Vitro and Ex Vivo Hair Follicle Models to Explore Therapeutic Options for Hair Regeneration," in Hair Follicle Regeneration, eds. F. Jimenez and C. Higgins (Cham: Springer International Publishing, 2022), 155-203.
- J. G. Toma, I. A. McKenzie, D. Bagli, and F. D. Miller, "Isolation and Characterization of Multipotent Skin-Derived Precursors From Human Skin," Stem Cells 23, no. 6 (2005): 727-737.
- A. Shafiee, J. Sun, I. A. Ahmed, et al., "Development of Physiologi- cally Relevant Skin Organoids From Human Induced Pluripotent Stem Cells," Small 20, no. 16 (2024): 2304879.
- J. G. Rheinwald and H. Green, "Serial Cultivation of Strains of Human Epidermal Keratinocytes: The Formation of Keratinizing Col- onies From Single Cells," Cell 6, no. 3 (1975): 331-343.
- J. A. Biernaskie, I. A. McKenzie, J. G. Toma, and F. D. Miller, "Isola- tion of Skin-Derived Precursors (SKPs) and Differentiation and Enrich- ment of Their Schwann Cell Progeny," Nature Protocols 1, no. 6 (2006): 2803-2812.
- R. Villani, S. Hodgson, J. Legrand, et al., "Dominant-Negative Sox18 Function Inhibits Dermal Papilla Maturation and Differentiation in all Murine Hair Types," Development 144, no. 10 (2017): 1887-1895.
- A. Irrthum, K. Devriendt, D. Chitayat, et al., "Mutations in the Tran- scription Factor Gene SOX18 Underlie Recessive and Dominant Forms of Hypotrichosis-Lymphedema-Telangiectasia," American Journal of Human Genetics 72, no. 6 (2003): 1470-1478.
- K. Arnold, A. Sarkar, M. A. Yram, et al., "Sox2+ Adult Stem and Progenitor Cells Are Important for Tissue Regeneration and Survival of Mice," Cell Stem Cell 9, no. 4 (2011): 317-329.
- Y. Yoshida, T. Soma, T. Matsuzaki, and J. Kishimoto, "Wnt Activator CHIR99021-Stimulated Human Dermal Papilla Spheroids Contribute to Hair Follicle Formation and Production of Reconstituted Follicle- Enriched Human Skin," Biochemical and Biophysical Research Commu- nications 516, no. 3 (2019): 599-605.
- C. A. Higgins, J. C. Chen, J. E. Cerise, C. A. B. Jahoda, and A. M. Christiano, "Microenvironmental Reprogramming by Three- Dimensional Culture Enables Dermal Papilla Cells to Induce De Novo Human Hair-Follicle Growth," Proceedings of the National Academy of Sciences 110, no. 49 (2013): 19679-19688.
- M. Hosseini, K. R. Koehler, and A. Shafiee, "Biofabrication of Human Skin With Its Appendages," Advanced Healthcare Materials 11, no. 22 (2022): 2201626.
- K. A. Horne, C. A. Jahoda, and R. F. Oliver, "Whisker Growth In- duced by Implantation of Cultured Vibrissa Dermal Papilla Cells in the Adult Rat," Development 97, no. 1 (1986): 111-124.
- A. Osada, T. Iwabuchi, J. Kishimoto, T. S. Hamazaki, and H. Oko- chi, "Long-Term Culture of Mouse Vibrissal Dermal Papilla Cells and De Novo Hair Follicle Induction," Tissue Engineering 13, no. 5 (2007): 975-982.
- S. B. Mahjour, F. Ghaffarpasand, and H. Wang, "Hair Follicle Re- generation in Skin Grafts: Current Concepts and Future Perspectives," Tissue Engineering Part B: Reviews 18, no. 1 (2011): 15-23.
- J. Wang, X. Wang, J. Xie, et al., "Engineered Skin Substitute Re- generates the Skin With Hair Follicle Formation," Biomedicine 9, no. 4 (2021): 400.
- Y. Sugiyama-Nakagiri, T. Fujimura, and S. Moriwaki, "Induction of Skin-Derived Precursor Cells From Human Induced Pluripotent Stem Cells," PLoS One 11, no. 12 (2016): e0168451.
- H. Sun, Y.-X. Zhang, and Y.-M. Li, "Generation of Skin Organoids: Potential Opportunities and Challenges," Frontiers in Cell and Develop- mental Biology 9 (2021): 3176.
Cited by
Sorted by citations
Mostina, 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-citation
- Authors
- Ahmed, I. A., Sun, J., Kong, M. J., Khosrotehrani, K., & Shafiee, A.
- Affiliations
- The University of Queensland (AU)
- Queensland Health (AU)
- Corresponding author
- Khosrotehrani, Kiarash
- Shafiee, Abbas
- Venue
- Experimental Dermatology
- Publisher
- Wiley
- Published
- 2024-11
- Volume
- 33
- Issue
- 11
- Pages
- e70017-e70017
- ISSN
- 0906-6705 (ISSN-L)
- 1600-0625
- OpenAlex
- W4404702663
- Cited by
- 7
- References
- 3
- Citations by year
- 2026: 4 · 2025: 3
- FWCI
- 3.31
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Experimental Dermatology (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- Metro North Hospital and Health Service
- Topics
- Health Sciences › Medicine › Urology › Hair Growth and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- skin-derived precursor cells, skin organoids, human induced pluripotent stem cells, cell isolation, self-renewal, SOX2, S100β, hair regrowth, wound healing, hair follicle neogenesis
- MeSH terms
- Cell Differentiation, Humans, Organoids, Pilot Projects, Skin, Hair Follicle, Multipotent Stem Cells, SOXB1 Transcription Factors, 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