Hair Follicle Organoids Using Human iPSC-Derived Ectodermal Precursor Cells for Hair Regenerative Medicine

Organoids containing hair follicles can be regenerated <i>in vitro</i> using human induced pluripotent stem cells (hiPSCs) and potentially used as a tissue graft for hair regeneration. There are two main approaches to organoid formation: one is to form embryoid bodies from hiPSCs and induce differentiation into several organs and tissues, and the other is to induce tissue precursor epithelial and mesenchymal cells from hiPSCs and coculture them to generate organs and tissues via epithelial-mesenchymal interaction. Our ultimate aim is to differentiate hiPSCs into hair follicle epithelial and mesenchymal stem cells, and to subsequently purify and use them to generate hair follicle organoids (HFOs). We previously showed that murine embryonic skin-derived stem cells could be used to generate mouse HFOs with ∼100% efficiency. However, the key to inducing mouse HFOs is the supplementation of Matrigel at very low concentrations, and this mouse tumor-derived matrix cannot be applied in human treatment. In the current study, we found that collagen I provided a microenvironment for inducing HFOs that was equivalent to that induced by Matrigel. Furthermore, hiPSCs were differentiated into human ectodermal precursor cells and subsequently used to generate human/mouse chimeric HFOs with mouse embryonic mesenchymal cells. The human/mouse chimeric HFOs showed hair follicle sprouting both <i>in vitro</i> and <i>in vivo</i>. Although another approach to induce human mesenchymal layer cells from hiPSCs is necessary to generate fully human HFOs, this study demonstrates the potential of employing hiPSC-derived ectodermal precursor cells (hiPSC-EPCs) in HFO cultures in hair regenerative medicine.