Researchers from the University of Pennsylvania School of Medicine have shown that it is possible for adult mice to grow new hair follicles.

The finding, published in the May 17 issue of Nature, catapults the idea of hair replacement from late-night infomercial to prime-time science. It also illustrates a somewhat sobering fact about science: that even issues as important as mammalian regeneration and as potentially lucrative as hair replacement can go uninvestigated for long periods of time in the first place.

"Things become a given and people don't think about it anymore. We certainly weren't thinking about it at all," when they made their discovery, senior author George Cotsarelis told BioWorld Today. Cotsarelis, an associate professor of dermatology at Penn, studies wound healing, and his team noticed in certain animal studies that "healing wounds developed hair. We thought something was wrong." But a review of old literature turned up several papers in the early 1950s describing hair regrowth in rabbits, mice and humans.

However, the technology available at the time did not allow the conclusive determination of whether the hair follicles were truly new or pre-existing. "There was a 10-year period of back and forth" in the literature, Cotsarelis said, that basically was put to rest when a review paper strongly - and, as it now turns out, incorrectly - argued that the phenomenon was not truly de novo hair growth.

Using transgenic mice, Cotsarelis and his team demonstrated through lineage analysis that the hair follicles they observed were really new structures derived from epidermal cells. While epidermal cells are the source of hair follicles during development, in adults, epidermis and hair have separate stem cells. Hair follicles are structures consisting of roughly 10 different cell types that are responsible for making glands as well as hair. Cotsarelis and his team observed that the new follicles made sebaceous glands as well as hair cells.

On a molecular level, wounding the mice appeared to induce an embryonic-like state in the skin covering the wounds, which made the skin receptive to signals that adult skin usually ignores. Cotsarelis and his team tested the developmental signaling molecule wnt, which plays a key role in hair development. They found that upregulating wnt expression in wounds more than doubled the number of hair follicles, while blocking wnt also blocked hair regrowth.

The data "refute the dogma" that adult hair regrowth is impossible, Cotsarelis said. They also suggested that regeneration of other body structures - currently an advantage of being an amphibian - might be feasible. Though the follicle often is referred to as a mini-organ, Cotsarelis said that the findings apply "not so much to solid organs, but perhaps limbs and digits, which express many of the same genes that follicles do."

Even without regrowing limbs, the studies have obvious commercial possibilities. Patents relating to the research have been licensed to start-up Follica Inc., of which Cotsarelis also is a co-founder, along with members of Boston Venture Capital group PureTech Ventures.

Follica hopes to be in a proof-of-concept human study on hair regeneration "within the year," PureTech managing partner and Follica CEO Daphne Zohar told BioWorld Today. But the company does not plan to limit itself to hair regrowth. Zohar described the hair follicle as "the master control center of human hair and skin," with applications ranging from the aesthetic, such as hair regrowth, to serious medical problems such as wound healing.

Cotsarelis said that "We've found that we can influence wound healing with wnts or other proteins that allow the skin to heal in a way that has less scarring and includes all the normal structures of the skin, such as hair follicles and oil glands, rather than just a scar."

The company is "not necessarily" targeting specifically the wnt pathway, PureTech principal and Follica Chief Business Officer David Steinberg told BioWorld Today. Cotsarelis' team also has implicated other molecular mechanisms in follicle regrowth, though Cotsarelis declined to specify them prior to peer-reviewed publication. Instead, Steinberg said, the company is based on the concept that inducing an embryonic-like state in skin will allow successful therapeutic manipulations that would have "no effect, or a different effect, on adult skin."

And despite the fact that the discovery of hair regrowth came as an offshoot of wound healing studies, the bald will not have to sacrifice their scalps to get some new hair. Steinberg said that Follica has done studies showing that the pathways that enable the follicle's embryonic-like response can be activated "by much, much less invasive means."

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