News
Nature Medicine - 12, 1397 - 1402 (2006)
Published online: 19 November 2006; | doi:10.1038/nm1504
Correction of junctional epidermolysis bullosa by
transplantation of genetically modified epidermal
stem cells
Fulvio Mavilio1, Graziella Pellegrini1,2, Stefano Ferrari2,
Francesca Di Nunzio1, Enzo Di Iorio2,
Alessandra Recchia1, Giulietta Maruggi1, Giuliana Ferrari3, Elena
Provasi4, Chiara Bonini4, Sergio Capurro5,
Andrea Conti6, Cristina Magnoni6, Alberto Giannetti6 e Michele De
Luca1,2
1Department of Biomedical Sciences, University of Modena and
Reggio Emilia, Via Campi 287, 41100 Modena, Italy. 2Epithelial Stem
Cell Research Center, Veneto
Eye Bank Foundation, H. SS Giovanni and Paolo, Castello 6777, 30100
Venice, Italy. 3Istituto Scientifico H. San Raffaele-Telethon
Institute for Gene Therapy (HSRTIGET)
and Vita-Salute University, and 4Cancer Immunotherapy and Gene
Therapy Program, Istituto Scientifico H. San Raffaele, Via Olgettina
58, 20132 Milano, Italy.
5Division of Plastic Surgery, H. San Martino, Largo Rosanna Benzi
10, 16132 Genova, Italy. 6Department of Internal Medicine,
University of Modena and Reggio
The continuous renewal of human epidermis is sustained by stem cells contained in the epidermal basal layer and in hair follicles1, 2. Cultured keratinocyte stem cells, known as holoclones3, 4, 5, 6, generate sheets of epithelium used to restore severe skin, mucosal and corneal defects7, 8, 9. Mutations in genes encoding the basement membrane component laminin 5 (LAM5) cause junctional epidermolysis bullosa (JEB), a devastating and often fatal skin adhesion disorder10. Epidermal stem cells from an adult patient affected by LAM5-3–deficient JEB were transduced with a retroviral vector expressing LAMB3 cDNA (encoding LAM5-3), and used to prepare genetically corrected cultured epidermal grafts.
 Nine grafts were transplanted onto prepared regions of the patient's legs by Timedsurgery(1). 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. 1) Guerra, L.,Capurro,S. et al. Treatment of ‘‘stable’’ vitiligo by Timedsurgery and transplantation of cultured epidermal autografts. Arch. Dermatol. 136, 1380–1389 (2000). Nine grafts were transplanted onto regions of the patient's legs prepared by timedsurgical de-epitelialisation. |