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Sci Transl Med. 2014 Nov 26;6(264):264ra163. doi: 10.1126/scitranslmed.3009540.

Human COL7A1-corrected induced pluripotent stem cells for the treatment of recessive dystrophic epidermolysis bullosa.

Author information

1
Institute for Stem Cell Biology and Regenerative Medicine, and Department of Pathology, Stanford University, Stanford, CA 94305, USA. Department of Obstetrics and Gynecology, Stanford University, Stanford, CA 94305, USA.
2
Program in Epithelial Biology, Department of Dermatology, Stanford University, Stanford, CA 94305, USA.
3
Institute for Stem Cell Biology and Regenerative Medicine, and Department of Pathology, Stanford University, Stanford, CA 94305, USA.
4
Department of Developmental Biology, Stanford University, Stanford, CA 94305, USA.
5
Institute for Regenerative Cures, School of Medicine, University of California, Davis, Sacramento, CA 95817, USA.
6
Departments of Pediatrics and Genetics, Stanford University, Stanford, CA 94305, USA.
7
Institute for Stem Cell Biology and Regenerative Medicine, and Department of Pathology, Stanford University, Stanford, CA 94305, USA. wernig@stanford.edu oro@stanford.edu.
8
Program in Epithelial Biology, Department of Dermatology, Stanford University, Stanford, CA 94305, USA. wernig@stanford.edu oro@stanford.edu.

Erratum in

  • Sci Transl Med. 2014 Dec 17;6(267):267er8. Derafshi, Bahareh Haddad [corrected to Haddad, Bahareh].

Abstract

Patients with recessive dystrophic epidermolysis bullosa (RDEB) lack functional type VII collagen owing to mutations in the gene COL7A1 and suffer severe blistering and chronic wounds that ultimately lead to infection and development of lethal squamous cell carcinoma. The discovery of induced pluripotent stem cells (iPSCs) and the ability to edit the genome bring the possibility to provide definitive genetic therapy through corrected autologous tissues. We generated patient-derived COL7A1-corrected epithelial keratinocyte sheets for autologous grafting. We demonstrate the utility of sequential reprogramming and adenovirus-associated viral genome editing to generate corrected iPSC banks. iPSC-derived keratinocytes were produced with minimal heterogeneity, and these cells secreted wild-type type VII collagen, resulting in stratified epidermis in vitro in organotypic cultures and in vivo in mice. Sequencing of corrected cell lines before tissue formation revealed heterogeneity of cancer-predisposing mutations, allowing us to select COL7A1-corrected banks with minimal mutational burden for downstream epidermis production. Our results provide a clinical platform to use iPSCs in the treatment of debilitating genodermatoses, such as RDEB.

PMID:
25429056
PMCID:
PMC4428910
DOI:
10.1126/scitranslmed.3009540
[Indexed for MEDLINE]
Free PMC Article

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