Strategies to utilize iPS cells for hair follicle regeneration and the treatment of hair loss disorders

The hair follicle (HF) is a mammalian skin structure that provides physical protection, detects sensation, and enables thermoregulation. In humans, loss of hairs on the head greatly affects the physical appearance, leading to altered quality of life. Thus, vast demand exists for treatments for hair loss disorders, represented by male and female pattern hair loss or alopecia areata. Regenerative medicine approaches, including HF bioengineering, can provide remedies for intractable hair loss diseases caused by irreversible HF destruction. The basis for experimental HF regeneration has been established in murine. However, human HF reconstitution adopting that principle has been hampered by the paucity of starting materials, including HF epithelial stem cells and hair-inductive dermal cells, and the loss of their HF-prone properties during in vitro expansion. With their high-proliferative capacity and multipotency, human induced pluripotent stem cells (hiPSCs) should be useful for HF regeneration. Indeed, hiPSC-derived epithelial and mesenchymal cells can contribute to in vivo HF-like structure regeneration. hiPSCs can also give rise to 3D integumentary organ systems comprising HFs which can be isolated and grafted onto areas of hair loss. Previous studies have focused mainly on the reproduction of HF structures; however, considering that the regeneration of complete HFs is not required to correct many common hair loss conditions, hiPSCs may be better differentiated into trichogenic dermal cells for cell-based therapy. For immune-mediated hair loss disorders, immunoregulatory cells can be induced from hiPSCs and inoculated into the affected lesion. In summary, hiPSCs are a promising cell source not only for HF bioengineering and but also for preparing cell populations that may be able to mitigate hair loss.