Use of Induced Pluripotent Stem Cells in Dermatological Research

Abstract

Induced pluripotent stem cells (iPSCs) have the potential to differentiate into any cell type of the body. iPSCs are generated through a process termed “reprogramming,” which entails the introduction of a set of transcription factors into somatic cells, such as dermal fibroblasts. iPSC clones, recognizable by their morphology (Figure 1a), arise from these cultures, usually within 14–21 days. In addition to their pluripotency, another important characteristic of iPSCs is that they can be propagated in cell culture indefinitely. Thus, an unlimited supply of iPSCs can be generated from a small skin biopsy. These iPSCs can then be differentiated into different types of somatic cells. For example, iPSCs can be directed to differentiate into epidermal keratinocytes, one of the cell types often affected in skin disorders. iPSC-derived keratinocytes can then be used to generate a stratified epidermis, either in vitro (3D skin equivalent cultures) or in vivo (xenotransplantation of keratinocytes onto immunodeficient mice; see Koch et al., 2014; Koster et al., 2014 for references). The ability to generate unlimited numbers of disease-specific keratinocytes provides an ideal tool for basic scientists to explore the molecular mechanisms underlying different skin disorders. Further, recently developed technologies now enable investigators to correct disease-causing mutations in iPSCs. These cells could then be used to generate gene-corrected, healthy replacement skin for patients affected by genetic skin disorders. A major advantage of this approach is that patients would be treated with cells that are unlikely to be immunologically rejected. Figure 1 Generation of induced pluripotent stem cells (iPSCs) and iPSC-derived keratinocytes