Bald Truth Is That Mice Can Regenerate Hair

PHILADELPHIA, May 17 -- In what may be good news for the bald, researchers here have shown that mice can regenerate hair follicles in much the same way that newts and salamanders can regrow body parts.

The finding may also have application in reducing scar tissue, said George Cotsarelis, M.D., of the University of Pennsylvania, and colleagues.

In genetically normal adult mice that suffered skin wounds, new hair follicles formed and went through the same developmental process as do embryonic follicles, the researchers reported in the May 17 issue of Nature.

Essentially, Dr. Cotsarelis said, the wound triggers an "embryonic state" in the healing skin, "which made it receptive to receiving instructions from wnt proteins" -- compounds known to be involved in hair-follicle development.

The new hair follicles were not derived from follicles that had previously been in the skin, the researchers found. Instead, they arose from other epidermal cells, under the guidance of the wnt proteins, Dr. Cotsarelis said.

The finding is unexpected, since most experts had thought that most mammals do not have the ability to regenerate tissue, according to Cheng-Ming Chuong, M.D., Ph.D., of the University of Southern California in Los Angeles, in an accompanying article. Dr. Chuong noted that, while salamanders and lizards can regenerate entire limbs, adult mammals have limited regenerative ability.

He also pointed out however that the event is similar to the regeneration of deer antlers. "After an antler is cast, the large open wound that forms is followed by re-epithelialization and the development of new hair follicles, as well as budding of the new antler."

The discovery by Dr. Cotsarelis and colleagues could "change our current understanding of repair and regeneration in adult mammals," Dr. Chuong said.

In the study, the researchers began by making wounds (whose area was one square centimeter) in the backs of three-week-old mice, to the full depth of the skin. By that age, the last of the animals' original hair follicles had formed, they said.

Within 11 days, the wounds had closed, leaving about a 0.25 square centimeter area that had an epidermis and dermis, but no evidence of hair follicles. But within 19 days after the wound, growths that resembled developing embryonic hair follicles were seen.

The same phenomenon was seen in adult mice, the researchers said, and the developing hair follicles went through all of the stages of embryonic follicle development.

Interestingly, the new hairs lacked pigment, because in mice the skin of the back does not have melanocytes, although the normally developed hair follicles do.

In genetically modified mice, the researchers induced expression of a protein that inhibits the wnt proteins from the time of the wound to 17 days later. While the wound healed normally, they found, hair follicles did not form.

In contrast, when they performed the experiment on mice genetically modified to over-express wnt proteins, the animals developed more than twice the number of new hair follicles as controls did.

At least in mice, the researchers said, "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."

Dr. Chuong cautioned that mice and people heal differently, so that the results can't be simply extrapolated. But, he said, the findings "will undoubtedly inspire new thinking in the management of alopecia, in tissue engineering, and in the regeneration of other organs."