Bioengineered follicles grow hair on bald mice

In a proof of concept study for bioengineered organ replacement, researchers in Japan made hair follicles derived from adult stem cells interact with surrounding tissue and show normal hair cycles, when transplanted into the skin of bald mice. Takashi Tsuji, a Professor in the Research Institute for Science and Technology, Tokyo University of Science, and Director of Organ Technologies Inc, led the team, who report their findings in an open access paper published in Nature Communications on 17 April. The study is significant on two counts: first it used adult stem cells and not embryonic stem cells, and second, the bioengineered follicles were fully functional and integrated into surrounding tissue, something that has not been managed before. Not only does the study raise hopes of a cure for baldness, the researchers say it also represents a significant advance toward the next generation of "organ replacement regenerative therapies" that will enable the replacement of organs damaged by disease, injury or aging. The researchers bioengineered hair follicle germ cells, the cells that mature into cells that grow hair, from two other types of cell: adult epithelial stem cells and dermal papilla cells. They implanted the bioengineered cells into the skin of hairless mice and showed that they went on to have normal hair cycles, where after dead hairs fell out, new ones took their place. The cells also showed other signs of normal functioning, such as piloerection, where the hair "stands on end" as a result of contraction of tiny surrounding muscles. The authors write that the bioengineered follicles showed these restored functions "through the rearrangement of follicular stem cells and their niches". This is important because the "niches", a loose term to describe the microenvironment of stem cells, are what regulate normal stem cell behavior: for instance, they decide when to wake up stem cells to mature into fully formed follicles. As well as demonstrating normal functioning, the bioengineered hair follicles developed the correct structures and made the right connections with surrounding tissue, including the epidermis, arrector pili muscles (the ones that produce piloerection) and nerve fibers. The authors write: "... our findings indicate that it is possible to not only restore a hair follicle but also to re-establish successful connections with the recipient skin by intracutaneous transplantation of the bioengineered follicle germ.""These findings significantly advance the technological development of bioengineered hair follicle regenerative therapy", and make a substantial contribution that will "enable future regenerative therapy for hair loss caused by injury or by diseases such as alopecia and androgenic alopecia". They call for further studies to find out how to optimize human hair follicle-derived stem cell sources for clinical applications, and for further investigations of stem cell niches, as these will contribute to the "development of hair regenerative therapy as a prominent class of organ replacement regenerative therapy in the future".