At Penn, the research is hair-raising, positively

Unlike salamanders, humans and other mammals are generally thought to be incapable of true regeneration - growing a new organ or limb when one has been lost entirely.

But yesterday, University of Pennsylvania dermatologists announced they had indeed performed this feat of biological renewal, regrowing complex "mini-organs" that are of pressing interest to millions of older men: the follicles that produce hair.

The researchers, who are publishing their findings today in the journal Nature, said that by carefully cutting out patches of skin in mice, they awakened a genetic pathway that normally remains dormant after embryonic development.

The shallow wounds stimulated new hair growth even though the follicles had been removed; the process worked especially well when researchers artificially boosted levels of a special signaling protein, senior author George Cotsarelis said.

They have not yet experimented on people, but already the wheels of commerce are churning. A startup company has licensed a patent based on the research. And the findings are of interest beyond the multibillion-dollar hair-loss industry, perhaps pointing to how doctors could do a better job healing burns and other wounds.

Bruce Morgan, an associate professor of dermatology at Harvard Medical School who was not involved with the research, called it "striking."

The authors "reprogrammed the cells to regenerate those organs from scratch," Morgan said.

Cotsarelis holds a stake in the startup company, aptly named Follica Inc., and is listed on the patent application with lead author Mayumi Ito, a postdoctoral fellow.

Why has this phenomenon not been widely recognized before now?

In a review accompanying the Nature report, the University of Southern California's Cheng-Ming Chuong offers a possible reason: Generating new follicles may require fairly large wounds, which in people are normally sutured or bandaged, perhaps impeding hair regrowth.

Cotsarelis urged people not to try this on themselves. Without the application of some substance formulated to boost the special protein pathway, he said, hair growth likely would not be robust.

"I'm kind of afraid of people misinterpreting this and incising the scalp," said Cotsarelis, an associate professor at Penn's School of Medicine. "Don't try this at home."

The cosmetics industry has been doing a robust business in transplanting hair follicles for years. Some companies, including one of which Cotsarelis is a board member, have begun trials that involve injecting cells to stimulate hair growth.

But the new approach - seemingly reconditioning skin cells to develop hair, much as they did in infancy - may one day make the most sense, said Harvard's Morgan.

"Far more desirable in the end would be to let them do what they know how to do in the first place," he said.

Though they regrew hair, the Penn researchers at first did not know where it came from. Through genetic analysis, they determined that the new follicles did not originate from adult stem cells in nearby existing follicles. Instead, they may have developed from adult stem cells that normally produce ordinary skin.

The Penn scientists were able to block the hair regrowth by inhibiting a molecular protein pathway, and likewise they significantly increased hair growth by boosting the signal.

Morgan said the research might point the way to better treatment for burn patients. Currently, doctors take healthy cells from elsewhere on the body, grow them in culture, and then graft them onto the burn site. But the grafts lack hair and sweat glands, and patients report that sensation is far from perfect.

The scar tissue that forms repairs on other kinds of wounds has similar drawbacks. Boosting the protein signal might help the body grow normal skin and hair over the wound instead of scar tissue, Cotsarelis said.

Still, there is much to do before the discovery can be studied in people. Mice heal somewhat differently from humans - closing wounds from the edge by contraction, while people rely more on filling the opening with new cells - but the authors are hopeful their findings will translate.

The hair-growth results appear to confirm a finding by another Penn dermatologist more than 50 years ago. That work was done by Albert Kligman, a professor emeritus who is better known for inventing the antiwrinkle cream Retin-A and for his now-controversial experiments on prisoners.

Kligman reported in 1956 that tiny new hairs grew in wounded skin - research that was viewed skeptically at the time.

"People made fun of that paper, because they said . . . the epidermis of an adult is incapable of producing new follicles," Kligman, now 91, said this week. "Sometimes, happily, you do something, and it sinks out of sight, and then it's rediscovered 50 years later."

Read more about the report via http://go.philly.com/science

EndText