Using an animal model, a research team led by Yann Barrandon at the EPFL (Ecole Polytechnique Federale de Lausanne) and the CHUV (Lausanne University Hospital) has discovered that certain cells inside the hair follicle are true multipotent stem cells, capable of developing into the many different cell types needed for hair growth and follicle replacement. In an article appearing in the Oct 3 advance online edition of the Proceedings of the National Academy of Sciences, they demonstrate that these holoclones can be used for long-term follicle renewal.
In 2001, Barrandon was part of a French research team who reported in the scientific journal Cell that stem cells could be used to generate skin containing hair and sebaceous glands in mice. But at that time it was unclear whether the stem cells in hair follicles were true stem cells, capable of long-term renewal, or multipotent progenitor cells that would not permanently engraft in the follicle.
In the current PNAS study, the Swiss researchers have answered that question, using rat whisker hair follicles to demonstrate that the clonogenic keratinocytes in hair follicles are true stem cells.
Barrandon’s group isolated stem cells from rat whisker follicles, labelled them, and grew them in culture for 140 generations. They then implanted progeny cells into the skin of newborn mice whose hair follicles were just being formed. This skin was then grafted onto athymic (nude) mice. Some cells were incorporated into developing follicles, but other follicles were completely made up of labelled cells. Each progeny cell contributed to the formation of eight different types of cell in the follicle, including those of the outer root sheath, inner root sheath, the hair shaft, the sebaceous gland and the epidermis.
After 125 days, a biopsy was taken from the graft, and labelled stem cells were isolated, subcloned, cultivated and then once again transplanted. The rat whisker stem cells participated again in forming all the cell types needed to form the hair follicle and sebaceous glands, resulting in hair bulbs that underwent repeated normal phases of growth, rest and regeneration. The fact that the transplanted cells participate in the hair cycle over long periods of time shows that they are true multipotent stem cells and not progeniture cells.
“With the progeny of a single stem cell, it would be theoretically possible to generate the complete hair bulb of a human being, and one that would last for years,” explains Barrandon.
The ability of the stem cells in hair follicles to repeatedly regenerate all the different cell types of the follicle and sebaceous glands has important implications for regenerative medicine. The method could one day be used to regenerate hair on patients with severe burns. This study is a logical complement to other work in Barrandon’s Laboratory of Stem Cell Dynamics, recognized for research into the reconstruction of injured tissues and organs.
