Editors' ChoiceStem Cells

New skin in the game

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Science Translational Medicine  22 Nov 2017:
Vol. 9, Issue 417, eaar2437
DOI: 10.1126/scitranslmed.aar2437


Transplantation of autologous transgenic stem cells resulted in near complete skin regeneration in a 7-year-old patient with severe junctional epidermolysis bullosa.

Junctional epidermolysis bullosa (JEB) is caused by mutations in genes encoding the basement membrane proteins LAMA3, LAMB3, or LAMC2, which are necessary for proper attachment of the epidermal layer of the skin to the underlying dermis. Skin lesions and blisters can form in JEB patients as the result of minor friction or rubbing. Patients are also at increased risk for infection, scarring, and skin cancer. In this study, Hirsch et al. report on the treatment of a 7-year-old JEB patient with a LAMB3 mutation who was admitted with a severe skin infection and epidermal loss on 60% of his body. Because of the drastic nature of the patient’s condition and after the failure of all available therapeutic approaches, a compassionate use of ex vivo cell and gene therapy was approved.

Small skin biopsies were taken from the patient and used to create primary keratinocyte cultures that were then treated with a retroviral vector encoding full length LAMB3 cDNA. From these transgenic stem cell cultures, sheets of epidermis were grown, either on plastic or on a fibrin substrate, and transplanted onto the patient. Both substrates were shown to support full engraftment of the cells after 10 days and complete epidermal regeneration after a month. Remarkably, 80% of the patient’s skin surface was replaced by transgenic cells. The researchers reported that the transgenic epidermis was stable, did not blister or itch, and healed normally. At the time of reporting, 21 months after treatment, the patient had no adverse effects from the treatment and his transplanted skin remained robust and elastic.

The patient did not form any tumors, and no genotoxicity was observed. In addition, the pattern of transgene integration that was observed clarified the way in which cells self-renew, showing that a small number of individual stem cells are responsible for skin cell renewal, rather than a large population of equally potent progenitor cells. Most importantly, this study showed that transgenic stem cells isolated from skin biopsies can efficiently engraft and self-renew, laying groundwork for other approaches using genetically modified stem cells.

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