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Restore hair, restore hearing

One local doctor is trying to reverse deafness by using stem cells to grow new hair in the inner ear

Few of us ever worry about the hair cells deep within our ears -- until it's too late. But gradually, either with age, exposure to loud noise or damage from medication, the few thousand hair cells with which each person is born die off, one-by-one, and hearing ability fades inexorably. Once the hair cells are gone, there's no getting them back.

The Holy Grail of hearing research has long been to find some way to replace or find a substitute for hair cells that have died. Decades of experiments have gone into sorting out why these cells are so vulnerable, and into finding ways to either save them or replace them.

Now, experiments being done at the Massachusetts Eye and Ear Infirmary suggest a solution may be possible. Research by Dr. Stefan Heller and his colleagues show that primitive stem cells can be coaxed to grow into mature hair cells. Eventually such stem cells may be implantable into the inner ears of deaf people to restore hearing.

According to neuroscientist Jeffrey Corwin at the University of Virginia, the results reported by Heller's team in December are opening new doors in hearing research. Heller's reports are "discoveries that I consider truly exciting," Corwin said. "Their results have provided the `proof of principle' for a new, accelerated approach to key research questions in the field."

Why is this research important? Because "hearing loss is perhaps the most prevalent of all the chronic diseases," Heller and three co-workers wrote in a recent issue of The Proceedings of the National Academy of Sciences. Hair cell death is the most common cause of the hearing loss that affects 28 million Americans.

Hearing loss is debilitating, expensive to treat and costly in terms of work time lost. It can be ameliorated somewhat with electronic hearing aids, and by the use of cochlear implant devices. But these methods are, at best, imperfect.

Corwin explained that chronic hearing problems arise because, unlike some other creatures, human "ears do not normally produce hair cells after birth."

But research has shown that hair cells can regrow, at least in some animals such as birds. So the trick is to find what controls this phenomenon, and see if regrowth can be awakened in the ears of mammals, or if new cells can be implanted. And stem cells, the cellular "seeds" from which an entire animal can be grown, provide a good place to start.

"It's an exciting time to be doing this research," Heller said, because so many powerful new tools are available for cell biology, and because the rules governing stem cell growth are becoming more apparent.

To be clear, the term "hair cell" has nothing to do with combs, curlers or coiffures and is really a misnomer because the tiny fibers that protrude from them are not ordinary hair at all. Instead, they act much like cats' whiskers, picking up tiny vibrations to help sense the environment.

The hair-like fibers inside the ear bend in response to sound and pressure waves inside the cochlea, generating electrical pulses that are sent on to the brain. In this role, hair cells serve as an exquisitely sensitive and critical link in how we hear and balance.

So far, however, the best approach to stemming hearing loss in humans is to keep what you're born with. Thus, the main defense is to avoid ear damage. State and federal noise standards exist to minimize damage from loud noises such as industrial machinery, gunfire and chain saws. Ear plugs and other sound-deadening devices are simple and effective, if used in time.

Peter S. Steyger, who is on the faculty at Oregon Health and Science University, has been making progress battling the other leading cause of hair cell death -- antibiotics. A handful of antibiotics, including gentamicin and streptomycin, which are prescribed about 400,000 times per year in the United States to treat premature babies and diseases like tuberculosis and meningitis, cause measurable hearing loss in roughly 20 percent of patients.

He has been developing medications that can be given along with the antibiotics, allowing them to work against the bacterial infection without killing hair cells. But he's excited by research like Heller's, too.

"When biological implants like the stem cells are available -- possibly not for a decade or two -- this will revolutionize the rehabilitation of sensi-neural hearing loss," Steyger said.

Last year, Heller's team reported in Nature Medicine that a small population of special cells exist in the inner ear -- adult stem cells -- that might somehow be induced to grow and replace hair cells that have died. More recently, they've run experiments with mouse embryonic stem cells showing that immature cells can be made to grow and form what seem to be new hair cells.

They also showed that these tiny mouse cells can be implanted into chicken embryos, where they mature and integrate into the inner ear's sensory patches. Then, "these progenitor cells can differentiate into hair cells" in the baby chick's ear, they said.

The mouse cells were able to become part of the developing chick's ear, Heller said in an interview, but it's not clear whether they formed the neural pathways necessary to create hearing and balance.

"We have not shown whether they actually become a functioning part of the chicken's ear," he said. "It will be an interesting experiment to see how the mouse cells behave in the chicken" after hatching, and whether "the cochlear hair cells can regenerate completely. Will the mouse cells follow the instructions from the chicken to regenerate?" He doesn't know yet.

Looking ahead, Heller said: "We can now see if it's possible to cure a mouse with hearing problems by replacing lost cochlear hair cells. That's the first step."

Another step will be to use human embryonic stem cells -- if he can get permission to use them, despite ethical concerns and restrictions created by the Bush administration -- to see if he can make the same process work in people.

In other experiments, his research team at the Eye and Ear Infirmary is trying to isolate adult stem cells -- those that are so mature they're already "committed" to becoming hair cells -- from human tissue. The source of these cells will be surgical procedures in which the specialized ear tissues are being removed for other reasons.

Some of the adult stem cells will be used to identify the chemical signals that could spur stem cells in the cochlea to begin growing to replace dead cells.

If that idea works, Heller said, then the signaling chemicals alone might be enough -- if given in the right doses in the right places -- to spur regrowth of hair cells in the cochlea -- and to solve a problem that now limits the quality of life of hundreds of millions of people around the world.

The causes of hearing loss

The main causes of hearing loss, which affects more than 28 million Americans:

1. At least 100 hereditary syndromes can lead to hearing loss.

2. Infections, such as bacterial meningitis and German measles, can affect hearing.

3. Acoustic trauma produced by sudden or long-term exposure to loud sounds is particularly common among construction workers, farmers, musicians, tree-cutters, airport workers and those in the armed forces, and causes hearing damage to roughly 100,000 people per year.

4. Prescription drugs, such as the antibiotics streptomycin and tobramycin, cause hearing damage to about 80,000 people per year. Anticancer drugs, such as cisplatin, and paint solvents affect nearly the same number.

5. Presbycusis, the hearing loss of old age, affects about one-third of people between 65 and 75, and nearly half of those over 75.

SOURCES: National Academy of Sciences, and Peter S. Steyger of Oregon Health and Science University

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