Generation of keratinocytes from normal and recessive dystrophic epidermolysis bullosa-induced pluripotent stem cells
Open accessAbstract
Embryonic stem cells (ESCs) have an unlimited proliferative capacity and extensive differentiation capability. They are an alternative source for regenerative therapies with a potential role in the treatment of several human diseases. The clinical use of ESCs, however, has significant ethical and biological obstacles related to their derivation from embryos and potential for immunological rejection, respectively. These disadvantages can be circumvented by the alternative use of induced pluripotent stem cells (iPSCs), which are generated from an individual's (autologous) somatic cells by exogenous expression of defined transcription factors and have biological characteristics similar to ESCs. In recent years, patient-specific iPSCs have been generated to study disease mechanisms and develop iPSC-based therapies. The development of iPSC-based therapies for skin diseases requires successful differentiation of iPSCs into cellular components of the skin, including epidermal keratinocytes. Here, we succeeded in generating iPSCs not only from normal human fibroblasts but also from fibroblasts isolated from the skin of two patients with recessive dystrophic epidermolysis bullosa. Moreover, we differentiated both of these iPSCs into keratinocytes with high efficiency, and generated 3D skin equivalents using iPSC-derived keratinocytes, suggesting that they were fully functional. Our studies indicate that autologous iPSCs have the potential to provide a source of cells for regenerative therapies for specific skin diseases.
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Skin organoids can be readily generated from patient-derived cells and used to model genetic disorders, such as epidermolysis bullosa.
“Furthermore, skin organoids can be readily generated from patient-derived cells and used to model genetic disorders, such as epidermolysis bullosa”
From Generation and characterization of hair-bearing skin organoids from human pluripotent stem cells (2022) · cites this paper as [62]
The Results and Discussion (pages not provided) show that the authors generated 3D skin equivalents from cells derived from patients with recessive dystrophic epidermolysis bullosa and used them as in vitro disease models. The paper calls these constructs skin equivalents, not organoids, and describes a multistep construction protocol; it does not establish that skin organoids can be readily generated. (LLM, conf=0.83)
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References 33 · Cited by 282
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- Authors
- Itoh, M., Kiuru, M., Cairo, M. S., & Christiano, A. M.
- Affiliations
- Columbia University Irving Medical Center (US)
- Columbia University (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2011-05-09
- Volume
- 108
- Issue
- 21
- Pages
- 8797-8802
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3102348
- OpenAlex
- W2120299070
- Cited by
- 282
- References
- 33
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 13 · 2023: 12 · 2022: 16 · 2021: 20 · 2020: 24 · 2019: 14 · 2018: 16 · 2017: 24 · 2016: 18 · 2015: 19 · 2014: 34 · 2013: 28 · 2012: 28
- FWCI
- 12.45
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- New York State Stem Cell Science
- National Institutes of Health
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (P30AR044535)
- Topics
- 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
- Health Sciences › Medicine › Urology › Hair Growth and Disorders
- Keywords
- induced pluripotent stem cells, keratinocytes, recessive dystrophic epidermolysis bullosa, keratinocyte differentiation, 3D skin equivalents, iPSC-based therapy, skin diseases, autologous cell therapy, fibroblasts, regenerative therapy
- MeSH terms
- Cell Differentiation, Fibroblasts, Humans, Skin Diseases, Keratinocytes, Epidermolysis Bullosa Dystrophica, Cell Culture Techniques, Regenerative Medicine, Induced Pluripotent Stem Cells
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