MIMIT seminar series - curing baldness

Curing Baldness –

Professor Ralf Paus

Hair loss/unwanted growth reflects problems in the hair follicle cycling due to problems i.e. malnutrition. The hair cycle is controlled by chemical signals and has three distinct phases; anagen (production), catagen (apoptosis) and telogen (rest). It was previously thought that hair follicles were only formed during fetal development, which is not true. Hair transplantations are used to fill in thinned scalp hair using micrografts and products that alter hair growth by conservation/preservation are available. The aim of hair research is to find a cure which is safe, inexpensive and minimally invasive.

Stem cells (SC’s) are responsible for producing hair follicles (HF’s) and the two SC populations are found in the bulge area and dermal papilla of the hair shaft. There are two main theories for hair restoration: cloning and regeneration/reactivation. General approach to cloning is to remove stem cells, multiply in suitable media and reinject new stem cells back to stimulate/produce new follicles. The SC populations can also be mixed together in culture to produce primitive follicle structures which are injected back into the scalp. Neogenesis (a fetal event) has been successful in mouse studies but not human whereas adult neogenesis is possible but problematic. Cell processing outside the body may produce undesirable results. Clinical problems such as painful cysts, granuloma and even skin cancer and cosmetic problems can occur; therefore hair needs to be strong, full pigmentation, voluminous and of correct orientation. On the other hand, current FDA approved drugs such as minoxidil and finasteride, prove follicular regeneration is possible. Even when hair follicles aren’t visible, stem cells are still present i.e. alopecia. Injecting these steroids into bald areas initiated re-growth, suggesting a reversible event; as follicles can be switched on/off.

An alternative approach would be to find biochemical messengers that control the on/off process of follicles. Other studies used mice experiments to investigate follicle behaviour where wounds were created in mouse skin, certain genes were turned on/off and during healing processes it was found that new hairs were formed. Prof Paus’ team suggest that regeneration of dormant follicles is a better method than travelling in a new direction like cloning and are currently working on TGFB/BMP signals during hair follicle development. Animal studies have been completed and the next stage is to start human clinical trials.

Prof Paus suggests that as well as looking regeneration of hair follicles, adult epithelial and mysenchymal hair follicle stem cells could be used for in vitro production of skin to cover defects via transplantation. Using potentially useful markers of the mouse system, immunohistochemistry, immunofluorescence, microarrays and proteomic analyses are used to select epithelial and mysenchymal stem cells containing hair follicle compartments. The discovery of epithelial stem cells (eSC’s) near the bulge region of the hair follicle have lead to the identification of a number of SC populations that are crucial to wound healing; providing an ideal model system for stem cell biology and identification of reliable stem cell markers.

To conclude; it is easier to conserve rather than surgically restore hair and hair cures are more likely to be found via methods of regeneration i.e. identifying biological chemical mediators for reactivation, as opposed to cloning of follicles. Stem cells have the potential to become anything and the hair follicle itself is a cell farm that is ideal for research in this rapidly advancing field.