Induced Pluripotent Stem Cell Approach to Hair Follicle Regeneration

Abstract

Introduction: Current surgical hair restoration procedures redistribute existing hair follicles from one area of the scalp to another without any net increase in follicle number. The discovery of induced pluripotent stem cells (iPSCs) by Shinya Yamanaka (Nobel Prize in Physiology or Medicine 2012) ushered in a new approach to regenerative medicine with relevance to hair loss. Here we focus on dermal papilla cells, which provide cues for hair follicle growth and cycling. We describe generation of human dermal papilla cells from iPSCs via a mesenchymal route or a neural crest intermediate and cover the spontaneous eruption of hair follicles in skin organoids. Methods: For the selection of literature covered in this chapter we used PubMed database and our own unpublished work. We used keywords such as hair follicle development, hair follicle regeneration, induced pluripotent stem cells, neural crest, 3D cultures, and hair organoids. Results: Functional dermal papilla cells can be generated from human pluripotent stem cells. Combination of pluripotent stem cell derived dermal papilla cells and epithelial stem cells (which can also be generated from human pluripotent stem cells) results in formation of 3 dimensional organoids, which elongate in the dish and form hair follicles upon transplantation into Nude mice. Spontaneous eruption of hair follicles from skin organoids in vitro represents an alternative approach to generate hair follicles from human pluripotent stem cells. Conclusions: The iPSC-based approach provides virtually unlimited source of folliculogenic cells for de novo formation of hair follicles. However, this approach to hair regeneration must still overcome several challenges that are common to other regenerative medicine protocols based on pluripotent stem cells.