AI Article Synopsis

  • RDEB is a severe skin condition caused by mutations in the collagen type VII gene, leading to skin blistering.
  • Genetically modified skin cells were successfully grafted onto two RDEB dogs, showing that one dog maintained a healthy, integrated epidermis for 24 months while the other faced graft failure due to lower efficiency in cell transduction.
  • The study demonstrates that effective gene therapy for RDEB relies on high transduction efficiency of skin stem cells, highlighting its potential for treating inherited skin disorders.

Article Abstract

Recessive dystrophic epidermolysis bullosa (RDEB) is a severe skin blistering condition caused by mutations in the gene coding for collagen type VII. Genetically engineered RDEB dog keratinocytes were used to generate autologous epidermal sheets subsequently grafted on two RDEB dogs carrying a homozygous missense mutation in the col7a1 gene and expressing baseline amounts of the aberrant protein. Transplanted cells regenerated a differentiated and vascularized auto-renewing epidermis progressively repopulated by dendritic cells and melanocytes. No adverse immune reaction was detected in either dog. In dog 1, the grafted epidermis firmly adhered to the dermis throughout the 24-month follow-up, which correlated with efficient transduction (100%) of highly clonogenic epithelial cells and sustained transgene expression. In dog 2, less efficient (65%) transduction of primary keratinocytes resulted in a loss of the transplanted epidermis and graft blistering 5 months after transplantation. These data provide the proof of principle for ex vivo gene therapy of RDEB patients with missense mutations in collagen type VII by engraftment of the reconstructed epidermis, and demonstrate that highly efficient transduction of epidermal stem cells is crucial for successful gene therapy of inherited skin diseases in which correction of the genetic defect confers no major selective advantage in cell culture.

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http://dx.doi.org/10.1038/jid.2011.172DOI Listing

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