Pluripotent stem cells as a cellular model for skin: relevance for physiopathology, cell/gene therapy and drug screening

The skin represents the largest tissue in the human body. Its external part, the epidermis, accomplishes vital functions such as barrier protection, thermoregulation and immune function. The mammalian skin epidermis has been for decades the paradigm for studying the molecular events that occur in tissue homeostasis and repair. Many genes and signaling pathways have been identified by the use of manipulated transgenic and KO mice. However, despite numerous elegant transgenic mice experiments, absence of an appropriate in vitro model system has hampered the molecular study of the early events responsible for epidermal and dermal commitments, stages at which congenital genetic alterations are responsible for hundreds of rare skin diseases. For most of them, etiology and treatment are still missing. Here we review the last decade of studies aimed at designing cellular models from pluripotent stem cells (PSC) that recapitulate in vitro the main molecular steps of skin formation. As described below, PSC-based models are powerful tools to (i) clarify early molecular events that occur during epithelial/mesenchymal interactions, (ii) produce in large amount skin cells that could become an alternative for cell/gene therapies and (iii) screen for therapeutic compounds to treat genodermatoses.