Concise review: Epidermal grafting: the case for pluripotent stem cells.

Although cell therapy has been clinically implemented for several decades, its use is hampered by the difficulty in supplying the amount of epidermal substitute needed to extend the application to all patients who may benefit from it. How human pluripotent stem cells may help meet this challenge is the topic of this review. After reporting on the main current applications and needs of skin grafting, we explore the potential of pluripotent stem cells--either of embryonic origin or produced by genetic reprogramming--to provide the needed clinical-grade keratinocytes, fulfilling industrial scale production, and quality standards. Immunogenicity is clearly an issue, although one may expect cells displaying characteristics of fetal or embryonic skin to have a much better tolerance than adult keratinocytes. The open possibility of a bank of pluripotent stem cell lines selected on the basis of interesting haplotypes may eventually provide a definitive answer. Actually, making the case for pluripotent stem cells in skin grafting goes well beyond that specific cell type. Most cell phenotypes that normally participate to the formation of dermis and epidermis can either already be obtained through in vitro differentiation from pluripotent stem cells or would likely migrate from the host into a graft. However, differentiation protocols for specialized glands and hair follicles remain to be designed. A future can be foreseen when reconstructive medicine will make use of composite grafts integrating several different cell types and biomaterials.