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Cited by 693Skin and Cellular Biology ResearchVirus-based gene therapy researchHair Growth and Disorders

Regeneration of the entire human epidermis using transgenic stem cells

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Hirsch, Tobias, Rothoeft, Tobias, Teig, Norbert, Bauer, Johann W., Pellegrini, Graziella, De Rosa, Laura, Scaglione, Davide, Reichelt, Julia +18 more·2017·Nature
DOI 10.1038/nature24487PMC PMC6283270
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Abstract

Junctional epidermolysis bullosa (JEB) is a severe and often lethal genetic disease caused by mutations in genes encoding the basement membrane component laminin-332. Surviving patients with JEB develop chronic wounds to the skin and mucosa, which impair their quality of life and lead to skin cancer. Here we show that autologous transgenic keratinocyte cultures regenerated an entire, fully functional epidermis on a seven-year-old child suffering from a devastating, life-threatening form of JEB. The proviral integration pattern was maintained in vivo and epidermal renewal did not cause any clonal selection. Clonal tracing showed that the human epidermis is sustained not by equipotent progenitors, but by a limited number of long-lived stem cells, detected as holoclones, that can extensively self-renew in vitro and in vivo and produce progenitors that replenish terminally differentiated keratinocytes. This study provides a blueprint that can be applied to other stem cell-mediated combined ex vivo cell and gene therapies.

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  • Transplantation of HSEs onto burn patients or recent transplantation of HSEs to cure junctional epidermolysis bullosa demonstrate their clinical importance and remains the gold standard.

    “transplantation of HSEs onto burn patients or recent transplantation of HSEs to cure junctional epidermolysis bullosa demonstrate their clinical importance and remains the gold standard.69”

    From Single-cell transcriptomics of human-skin-equivalent organoids (2023) · cites this paper as [69]

    The section ‘Regeneration of a functional epidermis by transgenic epidermal cultures’ (page not provided) says keratinocyte cultures have long been used to treat severe burns and reports regeneration of functional epidermis in one patient with junctional epidermolysis bullosa. The paper does not establish that HSE transplantation is the gold standard, and its JEB result is a single-patient treatment rather than a general cure. (LLM, conf=0.86)

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Cited by

Sorted by citations

Authors
Hirsch, T., Rothoeft, T., Teig, N., Bauer, J. W., Pellegrini, G., De Rosa, L., Scaglione, D., Reichelt, J., Klausegger, A., Kneisz, D., Romano, O., Secone Seconetti, A., Contin, R., Enzo, E., Jurman, I., Carulli, S., Jacobsen, F., Luecke, T., Lehnhardt, M., Fischer, M., Kueckelhaus, M., Quaglino, D., Morgante, M., Bicciato, S., Bondanza, S., & De Luca, M.
Affiliations
  • BG University Hospital Bergmannsheil Bochum (DE)
  • University Hospitals of the Ruhr-University of Bochum (DE)
  • Paracelsus Medical University (AT)
  • University of Modena and Reggio Emilia (IT)
  • Istituto di Genomica Applicata (IT)
  • University of Udine (IT)
ORCID
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2017-11
Volume
551
Issue
7680
Pages
327-332
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/nature24487
PMC
PMC6283270
OpenAlex
W2768054910
Cited by
693
References
4
Citations by year
2026: 34 · 2025: 33 · 2024: 63 · 2023: 61 · 2022: 77 · 2021: 106 · 2020: 102 · 2019: 97 · 2018: 107 · 2017: 12
FWCI
45.30
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • IRIS UNIMORE (University of Modena and Reggio Emilia) (submittedVersion, cc-by)
  • RePEc: Research Papers in Economics (submittedVersion)
  • Institutional Research Information System (University of Udine) (submittedVersion)
  • Padua Research Archive (University of Padova) (submittedVersion)
Funders
  • Fondazione Cassa di Risparmio di Modena
  • European Commission (2007-13)
  • Ministero dell’Istruzione, dell’Università e della Ricerca (CTN01_00177_888744)
  • Regione Emilia-Romagna (Asse 1 POR-FESR 2007-13)
  • DEBRA Austria
  • European Regional Development Fund (2007-13)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Skin and Cellular Biology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
  • Health Sciences › Medicine › Urology › Hair Growth and Disorders
Keywords
junctional epidermolysis bullosa, laminin-5, epidermal regeneration, epidermal stem cells, holoclones, clonal tracing, gene therapy, proviral integration, chronic wounds, skin cancer, stem cell self-renewal
MeSH terms
Cell Self Renewal, Epidermal Cells, Kalinin, Cell Differentiation, Child, Clone Cells, Epidermis, Humans, Male, Proviruses, Regeneration, Stem Cells, Keratinocytes, Cell Adhesion Molecules, Epidermolysis Bullosa, Junctional, Cell Lineage, Transgenes, Dermis, Cell Tracking

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