Aside from a few, fleeting empirical observations in the 1950s, adult mammals appear to be lacking regenerative abilities. Just ask anyone whose hair follicles have died—the result is baldness.
But there is a glimmer of hope for the hair-challenged among us. Scientists at the University of Pennsylvania report that new hair follicles formed on the backs of mice that had suffered open skin wounds. The finding could pave the way for use in regenerating human hair. In fact, that possibility appears so promising that members of the research team have formed a company to try to develop a product designed to do just that.
Researchers originally set out to determine how hair follicle stem cells react when the epidermis (outer layer of the skin) is punctured. Their results, published in this week's issue of Nature: during the healing process, the injured skin behaves like developing embryonic skin, says senior study author George Cotsarelis, an associate professor of dermatology at Penn.
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The reason this went unnoticed until now, Cotsarelis speculates, is because "people who study wounds don't care about the hair … which occurs [a few days after] wound closure."
When the researchers wounded the skin of lab mice, they observed a surprising series of events that occurred in the lesion, if no attempt was made to mend it. First, stem cells stored in both the epidermal and follicle reserves raced to the injury site to help regenerate the skin. Days later, hair follicles began to form near the wound's center. The follicles, interestingly, were actually formed by repurposed epidermal stem cells, rather than follicle stem cells, as would be expected. "I think, evolutionarily, the healing process has evolved to repair the skin as quickly as possible," Cotsarelis says, so it reprograms cells as needed to repair the broken skin—using both epidermal and follicle stem cells—and then to regenerate the hair.
In an accompanying editorial in Nature, Cheng-Ming Chuong, a pathologist at the Keck School of Medicine of the University of Southern California notes that previous studies showed that by combining cells from different tissue components under certain conditions "scales can turn into feathers, oral mucosa (the membrane covering structures inside the mouth) can turn into toothlike appendages, and even the corneal epithelium [in the eye] can become hair follicles."
This ability for follicle and epidermal stem cells to play unexpected roles in healing suggests that wound sites behave much the same way as skin in the developing fetus. Cutting the skin, researchers found, activates a class of about 20 growth factors in epidermal cells known as Wnt proteins. Although these proteins help maintain the natural cycle of follicle cells, they are not normally produced in adult epidermal cells. By artificially increasing Wnt levels in mice during wounding, the researchers managed to double the number of new follicles that sprouted at the damaged area. Conversely, blocking release of Wnt proteins prevented follicle regeneration.
The scientists are optimistic that the finding could lead to a salve or other product to combat human hair loss—and, perhaps, even to regenerate hair where the sun now shines by performing dermabrasion to the bald scalp and slathering ointment on the wounds.
"For this to become therapeutic, you'd probably have to find ways to activate the Wnt pathways with a topical agent," Cotsarelis says. He notes that he and his colleagues have founded a small start-up company called Follica to create a product that could be applied to injured skin as it heals to "activate the right pathways … [that trigger] follicle formation." Cotsarelis says the for-profit venture is now only doing preclinical experiments, but if all goes perfectly, there could be a product on the market in two to three years.