Correction of junctional epidermolysis bullosa by transplantation of genetically modified epidermal stem cells

By F. Mavilio, G. Pellegrini, S. Ferrari, F. Nunzio, E. Iorio, A. Recchia, Giulietta Maruggi, G. Ferrari, Elena Provasi, C. Bonini and 5 more. Nature Medicine, 2006

664 citations recorded by the source corpus.

The continuous renewal of human epidermis is sustained by stem cells contained in the epidermal basal layer and in hair follicles. Cultured keratinocyte stem cells, known as holoclones, generate sheets of epithelium used to restore severe skin, mucosal and corneal defects. Mutations in genes encoding the basement membrane component laminin 5 (LAM5) cause junctional epidermolysis bullosa (JEB), a devastating and often fatal skin adhesion disorder. Epidermal stem cells from an adult patient affected by LAM5-β3–deficient JEB were transduced with a retroviral vector expressing LAMB3 cDNA (encoding LAM5-β3), and used to prepare genetically corrected cultured epidermal grafts. Nine grafts were transplanted onto surgically prepared regions of the patient's legs. Engraftment was complete after 8 d. Synthesis and proper assembly of normal levels of functional LAM5 were observed, together with the development of a firmly adherent epidermis that remained stable for the duration of the follow-up (1 year) in the absence of blisters, infections, inflammation or immune response. Retroviral integration site analysis indicated that the regenerated epidermis is maintained by a defined repertoire of transduced stem cells. These data show that ex vivo gene therapy of JEB is feasible and leads to full functional correction of the disease.

Subfields: Biomaterials, Cell Biology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/689e11cbc0cd77a424c21ff230350893e5ab073f

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Citations in the corpus

• Burn wound healing and treatment: review and advancements (2015, background): “showed that sheets of epithelium grown from autologous holoclones or keratinocyte stem cells (modified genetically) could be used to treat a patient with junctional epidermolysis bullosa [121], demonstrating the power of this graft refinement.”
• Skin Wound Healing Process and New Emerging Technologies for Skin Wound Care and Regeneration (2020, background): “Mavilio et al., 2006, used epithelial stem cells, known as holoclones, in a patient with junctional epidermolysis bullosa (JEB).”
• Epithelial stem cells: turning over new leaves. (2007, positive): “The methods also hold promise when combined with ex vivo gene therapies to correct a variety of life-threatening genetic skin disorders, including blistering conditions (Mavilio et al., 2006).”
• State-of-the-art gene-based therapies: the road ahead (2011, methodology): “In an ongoing example of retrovirus-based treatment, human skin cells from an epidermolysis bullosa patient were implanted after ex vivo transduction of a corrective retroviral vecto”