Fully functional hair follicle organ regeneration using organ-inductive potential stem cells with an accessory mesenchymal cell population in an in vitro culture system

Organ morphogenesis is essential for not only integrated organ functions in the body but also the determination of adult-tissue stem cells and their niche. Only hair follicle organs can cyclically regenerate in the variable bulbous germinative region as a form of programmed organ regeneration in adults. Here, we identified a cell population, hair follicle organ-intrinsic mesenchymal cells, with PDGFRα⁺/Sca1⁺/CD34^high+ mesenchymal cells, from the boundary zone of the epithelial stem cell niche by using the organ germ method, which plays essential roles in entering and promoting the downgrowth phase of the hair cycle. The bioengineered hair follicle germ reconstituted from bulge region-derived epithelial stem cells, dermal papillae and mesenchymal cells has full functions, including downgrowth, full-size hair follicle regeneration and the hair cycle, both in in vitro artificial skin and after intracutaneous skin transplantation. This study provides significant contributions to the basic and medical science of adult organ-inductive potential stem cells and their niches in organ morphogenesis and the adult hair cycle.