Concise Review: Epidermal Grafting: The Case for Pluripotent Stem Cells

Abstract

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.

25 Years of Epidermal Stem Cell Research

“…Thus, iPS cells provide a novel approach to regenerative therapy for heritable skin diseases such as epidermolysis bullosa. A recent detailed review making a case for iPS cells for regenerative medicine is available (Lemaître et al, 2011). …”

Heterelogous expression of mutated HLA-G decreases immunogenicity of human embryonic stem cells and their epidermal derivatives

“…Skin is the largest organ of the body and acts as a protective barrier to harmful bacteria as well as thermal insults and chemical agents that can cause acute trauma and chronic wounds. Cell-based regenerative strategies using autologous keratinocytes have been used for the treatment of large burns (Lemaitre et al, 2011). However, this technique has several disadvantages such as donor site morbidity as well as a long waiting times for in vitro expansion of keratinocytes that leave patients at risk of dehydration and infection.…”

Potential applications of keratinocytes derived from human embryonic stem cells

“…Due to the crucial requirement for temporary coverage of the wound bed, tissue‐engineered ‘off‐the‐shelf’ clinical‐grade grafts would be favorable to treat patients with extensive skin injuries in real time . Current adopted clinical procedure to treat the severely burned patients involves the application of cadaver epidermal grafts or human allografts for several weeks .…”