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Miniaturized human hair follicle shows concentration of Prostaglandin D2 (in green). Credit: Garza and Cotsarelis/Penn Medicine)
Miniaturized human hair follicle shows concentration of Prostaglandin D2 (in green). Credit: Garza and Cotsarelis/Penn Medicine)

Researchers at the University of Pennsylvania, who were investigating the biological causes of androgenetic alopecia or common genetic hair loss, have discovered that levels of a certain inhibitor protein, called Prostaglandin D2 (PD2), are elevated in bald areas on the scalp. This discovery could be an important breakthrough in developing a medical hair loss treatment that regulates the production of the protein, or one that blocks it from attaching to its receptor protein.

Prostaglandins are a family of proteins that have a wide range of functions, including controlling cell growth and constricting and dilating muscle tissue. According to an article in ScienceDaily, the researchers had previously found evidence that something was inhibiting hair growth, but they did not expect to find prostaglandins involved in the miniaturization of hair follicles:

“Our findings were unexpected, as prostaglandins haven’t been thought about in relation to hair loss, yet it made sense that there was an inhibitor of hair growth, based on our earlier work looking at hair follicle stem cells,” said George Cotsarelis, MD, chair and professor of Dermatology, and senior author on the studies.

In men with androgenetic alopecia, Prostaglandin D2 was found to be three times higher in bald scalp tissue versus areas of the scalp with hair. Additionally, when hair follicles in a laboratory culture were treated with PD2, the hairs were significantly shorter than non-treated ones. A derivative of PD2, called 15-dPGJ2, was found to completely inhibit hair growth.

The receptor protein that is active with both prostaglandins, called GPR44, may hold the key to limiting the effects of PD2 and, therefore, in regulating hair loss in both men and women. While the study looked only at men, the GPR44 receptor protein exists in women as well. So, theoretically, a topical hair loss treatment may be developed that would prevent or limit thinning or hair loss in both sexes.

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Q: I know that both Aderans and Intercytex are doing research with cloning hair. Is there any difference in their approaches?

A: Aderans is using the “two-cell” approach. They feel that the best way to produce viable hair follicles is to use a combination of inducer cells and responder cells. Each would be multiplied separately and then injected together into the skin. The inducer cells are follicular fibroblasts and lie at the base of the hair follicle. The responder cells are keratinocytes. They feel that the combination of cells will have the best chance of producing clinically useful hair.

Intercytex prefers a one-cell approach. Their researchers feel that when the cultured inducer fibroblasts are injected into the skin there will be enough existing cells in the skin to produce a cosmetically viable hair. In their experimentation, Intercytex uses a new animal model, termed the “flap graft” model, that involves the implantation of cultured dermal papilla cells with keratinocytes placed under a flap on the back of hairless mice. Later the flap is exteriorized (turned over), allowing the hair to grow normally. Exactly how this will be applied to clinical use in humans is not clear.

A completely different view is held Dr. Ralf Paus at the University of Luebeck in Germany. He feels that there are already enough stem cells in the bald scalp and that the key to hair re-growth is to target key elements in the hair cycle. He feels that topically applied inhibitors of catagen (the resting phase of the hair cycle), exogen (the formation of an empty hair follicle), or inhibitors of the terminal-to-vellus transformation (the process of a hair shrinking in size under the influence of DHT and referred to as miniaturization) will the most effective way to go.

Finasteride and dutasteride are drugs that work in this way, but are clearly not very effective in stimulating new growth. He also feels that an anagen inducer, along the lines of a minoxidil-type medication has a better chance of success then the stem cell targeting strategies described above. In these cases one would, in a sense, rejuvenate dormant hair follicles rather than induce new ones to grow.

Read about Hair Cloning Methods

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