Training Hair Cells to Grow

Nude mice are the foot soldiers for the war on balding. These dainty pink-hued rodents have been bred or genetically altered to remain hairless throughout their lives. They can be ordered by the mischief-load from medical suppliers and endure poking and prodding and other unspeakable horrors for the sake of balding men everywhere.

In Philadelphia, Ken Washenik, M.D., Ph.D., executive vice president of scientific and medical development for Aderans Research Institute and a clinical assistant professor of dermatology at New York University's Langone Medical Center, shows me slides of nude mice on his laptop. They have undergone a new type of hair-cloning procedure that Dr. Washenik has been developing for Aderans. The company, which has its headquarters in Tokyo, is the world's largest manufacturer of wigs. It also owns Bosley, which operates 88 hair-transplant clinics in North America.

When I arrive at Aderans, Dr. Washenik hastily ushers me past several labs, perhaps wary I might glimpse some sort of trade secret, and into an empty conference room. What he does reveal is that his approach to hair cloning (he calls it follicular neogenesis) doesn't rely solely on dermal papillae. "We are using a two-cell construct, growing not just dermal papillae, but also another type of cell from the follicle," he explains.

As the thinking goes, disparate cell types already communicate with one another in the follicle to regenerate hair. Dr. Washenik believes that if he can re-create that environment in the lab, cultured cells won't get dementia and forget how to make hair. "The different cells in the follicle are smarter than we are," Dr. Washenik says. "They already know they are supposed to be hairy. In 8 days, we grew a ball of hair that never existed before on the back of a mouse."

Dr. Washenik clicks an image file on his computer: The photo shows what looks like Piglet with a sable Mohawk. But there is a caveat: "These were hair cells from a mouse that were injected into a mouse. When researchers injected human cells into a mouse, they didn't get the same results."

This disappointed Dr. Washenik and other researchers, because unlike other organs, follicles are supposed to be immune privileged: When transplanted across or between species, they're expected to grow normally, without being rejected or provoking infection. He hopes to have better luck in clinical trials, when he will transplant human cells into humans. Aderans is in the second phase of a human trial, which is expected to be completed by the end of the year.

The company is pouring serious cash (Dr. Washenik won't say how much) into its hair-cloning effort. Dr. Washenik is also intrigued by other researchers who are pursuing another pathway. They're cultivating in vitro microscopic hairs, or "proto-hairs," as Dr. Washenik dubs them. "These are early follicular structures that you can place in the scalp with the same technology that's used for a hair transplant," he says. "The big hurdle so far is getting the cells to multiply to make enough hair. Once we culture them, they sometimes die or de-differentiate."

But Dr. Washenik remains confident. "The sooner we figure this out, the better," he says. "So many people are waiting for this technology. I know that with every medical advance, the first one to market becomes the leader, and everyone else plays catch-up." Like many of the scientists I meet, his passion for a cure is personal. "I started going bald at 25," he says, tussling his hair to flaunt his 2,200-graft transplant. "While I was working on my Ph.D., I was mixing up homemade minoxidil [the active ingredient in Rogaine] in my lab."

A few blocks away is a start-up called Follica. One of its cofounders, George Cotsarelis, M.D., is a cutaneous biologist and associate professor of dermatology at the University of Pennsylvania. In 1990, Dr. Cotsarelis was investigating the biological mechanisms of skin regeneration. "I was studying stem cells and found a population of them in the hair follicle, in a strange area called 'the bulge,'" he tells me when I stop by his office at U. Penn's School of Medicine. "We didn't know the function of the area, and we almost blew it off."

From then on, Dr. Cotsarelis started paying more attention to hair follicles. After a series of more recent experiments on mice, he made two important discoveries. First, he found that bulge cells aid in the formation of new hair follicles, suggesting that these cells influence hair growth during embryonic development, when we were bobbing around in the womb. He also learned that, throughout our lives, these same stem cells awaken to mend minor cuts and burns, as well as deeper wounds in the skin. What baffled Dr. Cotsarelis is why, if a healing wound is populated with bulge stem cells, new follicles don't form. The answer would at least explain why hair doesn't grow from scars.

Dr. Cotsarelis conducted further studies designed to reveal what kinds of molecular compounds (e.g., hormones and proteins) are present during hair-follicle development in mice embryos and are also present in adult mice. A major one, which he wrote about in a 2007 Nature article, was something called Wnt (pronounced wint), a network of proteins first identified in fruit flies.

Curious, Dr. Cotsarelis applied Wnt to small lesions purposely cut into nude mice (such gracious, noble critters). To his shock, follicles formed and sprouted hair. So if a person is bald, the obvious strategy would seem to be to douse his scalp with Wnt and wait for hair to grow. "The problem is that Wnt is involved in a lot of other things, one of which is skin cancer," Dr. Cotsarelis says. "It's very tricky business."

The idea behind Follica is to develop a procedure in which a surgeon would lightly wound the scalp—something akin to microdermabrasion, an antiaging treatment—to disrupt the skin and then apply a compound that would influence hair development in the area. This would trick the cells into reverting to an embryonic state, one in which they are genetically pre-programmed to make hair rather than simply repair skin, as they're predisposed to do after we're born. "Just when cells are deciding, 'Do I make a hair follicle? Or do I make an epidermis?' we can influence them with a protein to go down a hair-follicle pathway."