title: Genetically corrected iPSCs as cell therapy for recessive dystrophic epidermolysis bullosa.
abstract: Recessive dystrophic epidermolysis bullosa (RDEB) is caused by mutations in the gene encoding type VII collagen, resulting in fragile skin and mucous membranes that blister easily in response to mechanical stress. Induced pluripotent stem cells (iPSCs) carry the potential to fundamentally change cell-based therapies for human diseases, in particular for RDEB, for which no effective treatments are available. To provide proof of principle on the applicability of iPSCs for the treatment of RDEB, we developed iPSCs from type VII collagen (Col7a1) mutant mice that exhibited skin fragility and blistering resembling human RDEB. Genetically repaired iPSCs could be differentiated into functional fibroblasts that reexpressed and secreted type VII collagen. Corrected iPSC-derived fibroblasts did not form tumors in vivo and could be traced up to 16 weeks after intradermal injection. Moreover, iPSC-based cell therapy resulted in faithful and long-term restoration of type VII collagen deposition at the epidermal-dermal junction of Col7a1 mutant mice. Intradermal injection of genetically repaired iPSC-derived fibroblasts restored the mechanical resistance to skin blistering in mice with RDEB, suggesting that RDEB skin could be effectively and safely repaired using iPSC-based cell therapy.
authors.affiliation: IMBA-Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Dr. Bohr-Gasse 3, 1030 Vienna, Austria.
authors.forename: Daniel
authors.initials: D
authors.lastname: Wenzel
authors.affiliation: IMBA-Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Dr. Bohr-Gasse 3, 1030 Vienna, Austria.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Bayerl
authors.affiliation: Department of Dermatology, Medical Center-University of Freiburg, 79104 Freiburg, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Nyström
authors.affiliation: Department of Dermatology, Medical Center-University of Freiburg, 79104 Freiburg, Germany.
authors.forename: Leena
authors.initials: L
authors.lastname: Bruckner-Tuderman
authors.affiliation: IMBA-Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Dr. Bohr-Gasse 3, 1030 Vienna, Austria. arabella.meixner@imba.oeaw.ac.at josef.penninger@imba.oeaw.ac.at.
authors.forename: Arabella
authors.initials: A
authors.lastname: Meixner
authors.affiliation: IMBA-Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Dr. Bohr-Gasse 3, 1030 Vienna, Austria. arabella.meixner@imba.oeaw.ac.at josef.penninger@imba.oeaw.ac.at.
authors.forename: Josef M
authors.initials: JM
authors.lastname: Penninger
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D024143:Collagen Type VII / Q000235:genetics; D016108:Epidermolysis Bullosa Dystrophica / Q000235:genetics* / Q000628:therapy*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D005808:Genes, Recessive; D056426:Genetic Loci; D015316:Genetic Therapy; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism* / Q000637:transplantation*; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains
chemical_list: C583886:Col7a1 protein, mouse; D024143:Collagen Type VII