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Nature. 2017 Nov 16;551(7680):327-332. doi: 10.1038/nature24487. Epub 2017 Nov 8.

Regeneration of the entire human epidermis using transgenic stem cells.

Author information

1
Department of Plastic Surgery, Burn Centre, BG University Hospital Bergmannsheil, Ruhr University Bochum, 44789 Bochum, Germany.
2
Department of Neonatology and Pediatric Intensive Care, University Children's Hospital, Ruhr University Bochum, 44791 Bochum, Germany.
3
EB House Austria and Department of Dermatology, University Hospital of the Paracelsus Medical University, 5020 Salzburg, Austria.
4
Department of Surgery, Medicine, Dentistry and Morphological Sciences, University of Modena and Reggio Emilia, 41124 Modena, Italy.
5
Center for Regenerative Medicine "Stefano Ferrari", Department of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy.
6
IGA Technology Services s.r.l., 33100 Udine, Italy.
7
Department of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy.
8
Istituto di Genomica Applicata and Dipartimento di Scienze Agroalimentari, Ambientali e Animali, University of Udine, 33100 Udine, Italy.
9
Holostem Terapie Avanzate s.r.l., 41125 Modena, Italy.
10
Department of Neuropaediatrics, University Children's Hospital, Ruhr University Bochum, 44791 Bochum, Germany.

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.

PMID:
29144448
PMCID:
PMC6283270
DOI:
10.1038/nature24487
[Indexed for MEDLINE]

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