Regeneration of the entire human epidermis using transgenic stem cells

Tobias Hirsch, Tobias Rothoeft, Norbert Teig, Johann W. Bauer, Graziella Pellegrini, Laura De Rosa, Davide Scaglione, Julia Reichelt, Alfred Klausegger, Daniela Kneisz, Oriana Romano, Alessia Secone Seconetti, Roberta Contin, Elena Enzo, Irena Jurman, Sonia Carulli, Frank Jacobsen, Thomas Luecke, Marcus Lehnhardt, Meike Fischer, Maximilian Kueckelhaus, Daniela Quaglino, Michele Morgante, Silvio Bicciato, Sergio Bondanza and Michele De Luca ()
Additional contact information
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
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

Nature, 2017, vol. 551, issue 7680, 327-332

Abstract: 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.

Date: 2017
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DOI: 10.1038/nature24487

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