3D in vitro model of a functional epidermal permeability barrier from human embryonic stem cells and induced pluripotent stem cells

Anastasia Petrova, Anna Celli, Laureen Jacquet, Dimitra Dafou, Debra Crumrine, Melanie Hupe, Matthew Arno, Carl Hobbs, Aleksandra Cvoro, Panagiotis Karagiannis, Liani Devito, Richard Sun, Lillian C. Adame, Robert Vaughan, John A. McGrath, Theodora M. Mauro, Dusko Ilic

Research output: Contribution to journalArticle

71 Scopus citations

Abstract

Cornification and epidermal barrier defects are associated with a number of clinically diverse skin disorders. However, a suitable in vitro model for studying normal barrier function and barrier defects is still lacking. Here, we demonstrate the generation of human epidermal equivalents (HEEs) from human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs). HEEs are structurally similar to native epidermis, with a functional permeability barrier. We exposed a pure population of hESC/iPSC-derived keratinocytes, whose transcriptome corresponds to the gene signature of normal primary human keratinocytes (NHKs), to a sequential high-to-low humidity environment in an air/liquid interface culture. The resulting HEEs had all of the cellular strata of the human epidermis, with skin barrier properties similar to those of normal skin. Such HEEs generated from disease-specific iPSCs will be an invaluable tool not only for dissecting molecular mechanisms that lead to epidermal barrier defects but also for drug development and screening.

Original languageEnglish (US)
Pages (from-to)675-689
Number of pages15
JournalStem Cell Reports
Volume2
Issue number5
DOIs
StatePublished - May 6 2014

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

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