title: Long-term stability and safety of transgenic cultured epidermal stem cells in gene therapy of junctional epidermolysis bullosa.
abstract: We report a long-term follow-up (6.5 years) of a phase I/II clinical trial envisaging the use of autologous genetically modified cultured epidermal stem cells for gene therapy of junctional epidermolysis bullosa, a devastating genetic skin disease. The critical goals of the trial were to evaluate the safety and long-term persistence of genetically modified epidermis. A normal epidermal-dermal junction was restored and the regenerated transgenic epidermis was found to be fully functional and virtually indistinguishable from a normal control. The epidermis was sustained by a discrete number of long-lasting, self-renewing transgenic epidermal stem cells that maintained the memory of the donor site, whereas the vast majority of transduced transit-amplifying progenitors were lost within the first few months after grafting. These data pave the way for the safe use of epidermal stem cells in combined cell and gene therapy for genetic skin diseases.
authors: Center for Regenerative Medicine "Stefano Ferrari," Department of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy.
authors: Laura
authors: L
authors: De Rosa
authors: Center for Regenerative Medicine "Stefano Ferrari," Department of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy.
authors: Sonia
authors: S
authors: Carulli
authors: Center for Regenerative Medicine "Stefano Ferrari," Department of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy.
authors: Fabienne
authors: F
authors: Cocchiarella
authors: Department of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy.
authors: Daniela
authors: D
authors: Quaglino
authors: Center for Regenerative Medicine "Stefano Ferrari," Department of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy.
authors: Elena
authors: E
authors: Enzo
authors: Center for Regenerative Medicine "Stefano Ferrari," Department of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy.
authors: Eleonora
authors: E
authors: Franchini
authors: Emeritus of Dermatology, University of Modena and Reggio Emilia, 41125 Modena, Italy.
authors: Alberto
authors: A
authors: Giannetti
authors: Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy.
authors: Giorgio
authors: G
authors: De Santis
authors: Center for Regenerative Medicine "Stefano Ferrari," Department of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy.
authors: Alessandra
authors: A
authors: Recchia
authors: Center for Regenerative Medicine "Stefano Ferrari," Department of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy.
authors: Graziella
authors: G
authors: Pellegrini
authors: Center for Regenerative Medicine "Stefano Ferrari," Department of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy.
authors: Michele
authors: M
authors: De Luca
mesh_terms: D002478:Cells, Cultured; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism / Q000473:pathology; D016109:Epidermolysis Bullosa, Junctional / Q000628:therapy*; D005500:Follow-Up Studies; D015316:Genetic Therapy; D006801:Humans; D039161:Integrin alpha6beta4 / Q000378:metabolism; D053547:Keratin-14 / Q000378:metabolism; D007797:Laminin / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism; D012038:Regeneration; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
chemical_list: D039161:Integrin alpha6beta4; D053547:Keratin-14; D007797:Laminin; D011498:Protein Precursors; C032253:involucrin