Induced Pluripotent Stem Cells from Individuals with Recessive Dystrophic Epidermolysis Bullosa
Open accessAbstract
Recessive dystrophic epidermolysis bullosa (RDEB) is an inherited blistering skin disorder caused by mutations in the COL7A1 gene-encoding type VII collagen (Col7), the major component of anchoring fibrils at the dermal-epidermal junction. Individuals with RDEB develop painful blisters and mucosal erosions, and currently, there are no effective forms of therapy. Nevertheless, some advances in patient therapy are being made, and cell-based therapies with mesenchymal and hematopoietic cells have shown promise in early clinical trials. To establish a foundation for personalized, gene-corrected, patient-specific cell transfer, we generated induced pluripotent stem (iPS) cells from three subjects with RDEB (RDEB iPS cells). We found that Col7 was not required for stem cell renewal and that RDEB iPS cells could be differentiated into both hematopoietic and nonhematopoietic lineages. The specific epigenetic profile associated with de-differentiation of RDEB fibroblasts and keratinocytes into RDEB iPS cells was similar to that observed in wild-type (WT) iPS cells. Importantly, human WT and RDEB iPS cells differentiated in vivo into structures resembling the skin. Gene-corrected RDEB iPS cells expressed Col7. These data identify the potential of RDEB iPS cells to generate autologous hematopoietic grafts and skin cells with the inherent capacity to treat skin and mucosal erosions that typify this genodermatosis.
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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 [61]
The Results section reports that patient-derived RDEB iPS cells formed skin-like structures within teratomas, and the Discussion describes their potential for modeling RDEB. The paper does not report readily generating skin organoids; its skin-like structures formed in vivo after injection into mice. (LLM, conf=0.88)
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Self-citation
- Authors
- Tolar, J., Xia, L., Riddle, M. J., Lees, C. J., Eide, C. R., McElmurry, R. T., Titeux, M., Osborn, M. J., Lund, T. C., Hovnanian, A., Wagner, J. E., & Blazar, B. R.
- Affiliations
- University of Minnesota (US)
- Hôpital Necker-Enfants Malades (FR)
- Corresponding author
- Tolar, Jakub
- ORCID
- Venue
- Journal of Investigative Dermatology
- Publisher
- Elsevier BV
- Published
- 2011-04
- Volume
- 131
- Issue
- 4
- Pages
- 848-856
- ISSN
- 0022-202X (ISSN-L)
- PMC
- PMC4151825
- OpenAlex
- W2126016558
- Cited by
- 155
- References
- 2
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 2 · 2022: 5 · 2021: 9 · 2020: 3 · 2019: 7 · 2018: 6 · 2017: 12 · 2016: 13 · 2015: 13 · 2014: 20 · 2013: 17 · 2012: 23
- FWCI
- 7.68
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Investigative Dermatology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- University of Minnesota
- National Cancer Institute (P01CA065493)
- National Center for Research Resources (S10RR016851)
- 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
- recessive dystrophic epidermolysis bullosa, induced pluripotent stem cells, type VII collagen, COL7A1 mutations, anchoring fibrils, basement membrane zone, gene correction, hematopoietic differentiation, skin regeneration, epigenetic reprogramming, autologous cell therapy, genodermatosis
- MeSH terms
- Cell Differentiation, Cells, Cultured, Fibroblasts, Genes, Recessive, Humans, Keratinocytes, Epidermolysis Bullosa Dystrophica, Hematopoietic Stem Cell Transplantation, Collagen Type VII, Pluripotent Stem Cells, Epigenesis, Genetic, Mesenchymal Stem Cell Transplantation, Precision Medicine, In Vitro Techniques
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