The hair follicles regenerated through bioengineered hair follicle germs functionally integrated with the surrounding tissues, reproducing the natural hair orientation (hair stream) and restoring sensory perception through nerve innervation. Furthermore, the regenerated follicles underwent programmed postnatal regeneration, known as the hair cycle, and continued to repeat the cycle for as long as the transplanted mice lived. These findings suggest that hair follicle regeneration using bioengineered follicle germs may provide a one-time, lifelong treatment.
■ A transplantation model under the molar tooth cavity in vivo
The invention of the Organ Germ Method has made it possible to study functional organ regeneration in vivo.
In 2009, we demonstrated that by using epithelial and mesenchymal stem cells harvested from embryonic tooth germs (the ‘seeds’ of teeth), a bioengineered tooth germ generated through the Organ Germ Method could be transplanted into a tooth-loss site, leading to the local regeneration of a fully functional tooth. The regenerated tooth not only possessed the natural structure of a tooth but also restored functions mediated by the periodontal ligament, such as tooth mobility and sensory perception. This achievement significantly heightened societal expectations for organ regeneration therapy in dentistry.
However, since postnatal stem cells capable of regenerating teeth have not yet been identified, and because in humans it takes several years for permanent teeth to erupt, we have turned our focus toward refining current therapeutic approaches with the aim of realizing near-future tooth regeneration.
■ Hair follicle regeneration
Hair plays an important role as a social symbol, and alopecia significantly affects people’s quality of life (QOL). For this reason, extensive research has long been conducted on the mechanisms underlying hair loss as well as on the development of various therapeutic approaches. Entering the 21st century, stem cell research advanced dramatically, and studies focusing on hair follicle stem cells also made substantial progress.
The hair follicle is unique in that it possesses stem cells with organ-inductive potential, owing to its cyclical regeneration during the hair cycle. As such, the realization of hair follicle organ regeneration is anticipated as a pioneering step in next-generation regenerative medicine.
In 2012, we demonstrated that epithelial stem cells and mesenchymal cells-specifically dermal papilla cells-isolated from hair follicles could be used to generate bioengineered hair follicle germs through the Organ Germ Method. When transplanted into hair-bearing skin, these bioengineered follicle germs successfully regenerated functional hair follicles at the local site.
■ Toward Business Development
The invention of the Organ Germ Method made it possible to conduct research on functional organ regeneration within living organisms. By isolating epithelial stem cells and mesenchymal stem cells with organ-forming potential from fetal tooth germs (essentially “seeds of teeth”), we created bioengineered tooth germs using this method. When these regenerated tooth germs were transplanted into edentulous sites, teeth successfully erupted. These regenerated teeth were structurally equivalent to natural teeth and demonstrated the full restoration of physiological functions such as tooth movement and sensation, thereby confirming them as truly functional teeth.
Similarly, by isolating two types of organ-forming stem cells from fetal hair follicles (the organ that produces hair), salivary glands, and lacrimal glands, we were able to generate regenerated organ germs. When transplanted into the corresponding sites in vivo, these organ germs successfully achieved functional regeneration.
We were the first in the world to demonstrate functional organ regeneration from a broad range of regenerated organ germs, an achievement that drew considerable global attention. Among these regenerated organs, we selected tooth and hair follicle regeneration as priority targets for early feasibility and are advancing research and development toward commercialization.
At the same time, since hair follicles are located within the skin, we extended our research to develop three-dimensional artificial skin that reproduces the in vivo microenvironment. Skin is a major target tissue in the pharmaceutical and healthcare sectors and encompasses a complex organ system that includes hair follicles, sebaceous glands, and sweat glands. We are further advancing this technology both as research and development support tools and as therapeutic applications for severe burn injuries and skin disorders.
