3D In Vitro Model of a Functional Epidermal Permeability Barrier from Human Embryonic Stem Cells and Induced Pluripotent Stem Cells
Authors
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, and Dusko Ilic
Institution
Kings College London
Country
United Kingdom
Year
2014
Journal
Stem Cell Reports
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.