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Regeneration of the entire human epidermis using transgenic stem cells.
- Source :
-
Nature [Nature] 2017 Nov 16; Vol. 551 (7680), pp. 327-332. Date of Electronic Publication: 2017 Nov 08. - Publication Year :
- 2017
-
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.
- Subjects :
- Cell Adhesion Molecules genetics
Cell Adhesion Molecules metabolism
Cell Differentiation
Cell Lineage
Cell Self Renewal
Cell Tracking
Child
Clone Cells cytology
Clone Cells metabolism
Dermis cytology
Dermis pathology
Epidermis pathology
Epidermolysis Bullosa, Junctional genetics
Epidermolysis Bullosa, Junctional metabolism
Epidermolysis Bullosa, Junctional pathology
Humans
Keratinocytes cytology
Keratinocytes metabolism
Keratinocytes transplantation
Male
Proviruses genetics
Kalinin
Epidermal Cells
Epidermolysis Bullosa, Junctional therapy
Regeneration
Stem Cells cytology
Stem Cells metabolism
Transgenes genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1476-4687
- Volume :
- 551
- Issue :
- 7680
- Database :
- MEDLINE
- Journal :
- Nature
- Publication Type :
- Academic Journal
- Accession number :
- 29144448
- Full Text :
- https://doi.org/10.1038/nature24487