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

Vittorio Sebastiano, Hanson Hui Zhen, Bahareh Haddad Derafshi, Elizaveta Bashkirova, Sandra P. Melo, Pei Wang, Thomas L. Leung, Zurab Siprashvili, Andrea Tichy, Jiang Li, Mohammed Ameen, John Hawkins, Susie Lee, Lingjie Li, Aaron Schwertschkow, Gerhard Bauer, Leszek Lisowski, Mark A. Kay, Seung K. Kim, Alfred T. LaneMarius Wernig, Anthony E. Oro

Research output: Contribution to journalArticlepeer-review

142 Scopus citations


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-predisposingmutations, allowing us to select COL7A1-corrected banks withminimal mutational burden for downstream epidermis production. Our results provide a clinical platform to use iPSCs in the treatment of debilitating genodermatoses, such as RDEB.

Original languageEnglish (US)
JournalScience translational medicine
Issue number264
StatePublished - Nov 26 2014

ASJC Scopus subject areas

  • Medicine(all)


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