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Regeneration of the entire human epidermis using transgenic stem cells

Author

Listed:
  • Tobias Hirsch

    (Burn Centre, BG University Hospital Bergmannsheil, Ruhr University Bochum)

  • Tobias Rothoeft

    (University Children’s Hospital, Ruhr University Bochum)

  • Norbert Teig

    (University Children’s Hospital, Ruhr University Bochum)

  • Johann W. Bauer

    (University Hospital of the Paracelsus Medical University)

  • Graziella Pellegrini

    (Medicine, Dentistry and Morphological Sciences, University of Modena and Reggio Emilia
    Center for Regenerative Medicine “Stefano Ferrari”, University of Modena and Reggio Emilia)

  • Laura De Rosa

    (Center for Regenerative Medicine “Stefano Ferrari”, University of Modena and Reggio Emilia)

  • Davide Scaglione

    (IGA Technology Services s.r.l.)

  • Julia Reichelt

    (University Hospital of the Paracelsus Medical University)

  • Alfred Klausegger

    (University Hospital of the Paracelsus Medical University)

  • Daniela Kneisz

    (University Hospital of the Paracelsus Medical University)

  • Oriana Romano

    (University of Modena and Reggio Emilia)

  • Alessia Secone Seconetti

    (Center for Regenerative Medicine “Stefano Ferrari”, University of Modena and Reggio Emilia)

  • Roberta Contin

    (Center for Regenerative Medicine “Stefano Ferrari”, University of Modena and Reggio Emilia)

  • Elena Enzo

    (Center for Regenerative Medicine “Stefano Ferrari”, University of Modena and Reggio Emilia)

  • Irena Jurman

    (Ambientali e Animali, University of Udine)

  • Sonia Carulli

    (Holostem Terapie Avanzate s.r.l.)

  • Frank Jacobsen

    (Burn Centre, BG University Hospital Bergmannsheil, Ruhr University Bochum)

  • Thomas Luecke

    (University Children’s Hospital, Ruhr University Bochum)

  • Marcus Lehnhardt

    (Burn Centre, BG University Hospital Bergmannsheil, Ruhr University Bochum)

  • Meike Fischer

    (University Children’s Hospital, Ruhr University Bochum)

  • Maximilian Kueckelhaus

    (Burn Centre, BG University Hospital Bergmannsheil, Ruhr University Bochum)

  • Daniela Quaglino

    (University of Modena and Reggio Emilia)

  • Michele Morgante

    (Ambientali e Animali, University of Udine)

  • Silvio Bicciato

    (University of Modena and Reggio Emilia)

  • Sergio Bondanza

    (Holostem Terapie Avanzate s.r.l.)

  • Michele De Luca

    (Center for Regenerative Medicine “Stefano Ferrari”, University of Modena and Reggio Emilia)

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.

Suggested Citation

  • Tobias Hirsch & Tobias Rothoeft & Norbert Teig & Johann W. Bauer & Graziella Pellegrini & Laura De Rosa & Davide Scaglione & Julia Reichelt & Alfred Klausegger & Daniela Kneisz & Oriana Romano & Aless, 2017. "Regeneration of the entire human epidermis using transgenic stem cells," Nature, Nature, vol. 551(7680), pages 327-332, November.
    • Handle: RePEc:nat:nature:v:551:y:2017:i:7680:d:10.1038_nature24487
    DOI: 10.1038/nature24487
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    Cited by:

    1. Faust, Alice & Woydack, Lena & Strech, Daniel, 2023. "Should the governance of individual treatment attempts (“Individuelle Heilversuche”) include praxis evaluation? Results from qualitative stakeholder interviews," Health Policy, Elsevier, vol. 130(C).

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