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Stem cells may help treat loss of hearing

Early research on mouse hair cells shows promise

Milwaukee Journal Sentinel

Last Updated: Oct. 28, 2003

Pointing the way to possible new deafness and hearing loss treatments, researchers at Harvard Medical School have created inner ear hair cells from mouse embryonic stem cells.

The hairs have been both created in petri dishes and transplanted into the developing ears of chicken embryos.

Considering that about 80% of cases of human hearing loss are related to damaged or destroyed inner ear hair cells, the finding could have implications and applications for treating deafness, said Stefan Heller, one of the investigators and authors of the paper appearing in the Proceedings of the National Academy of Sciences this week.

The director of the National Institute on Deafness and Other Communication Disorders agreed.

"I think this is a wonderful piece of work," said James Battey, who also is chairman of the National Institutes of Health Stem Cell Task Force. "My sincere congratulations goes out to them. This is a real feat."

However, he did question some of the results and cautioned that the research is still in its infancy.

Heller and his co-investigators at Harvard's Massachusetts Eye and Ear Infirmary had been looking for ways to treat hearing loss.

Because damaged hairs in the inner ear are the leading culprits in deafness, investigators have long wanted to find treatments designed to prevent or restore their loss.

Inner ear hairs can be destroyed by extended exposure to loud noise, a sudden burst of sound, and certain medicines and diseases. And once damaged, they can't be repaired or regenerated, Heller said.

Treatments difficult

And because of the anatomy of the inner ear, finding treatments that focus on hair loss has proved difficult.

"The ear is very hard to dissect," Heller said. "It is well-hidden in the skull."

Indeed, most treatments for hearing loss have relied on external sound amplifiers - hearing aids - and cochlear implants, electronic devices inserted into the inner ear that send sound-generated electrical pulses directly to the brain.

And although cochlear implants can enable a deaf person to understand spoken language - even over the phone - the hearing isn't the same as that in non-hearing-impaired people, said Battey.

But if a treatment could be found that focused on repairing and replacing damaged hair cells, it is conceivable that a patient suffering from hearing loss could retain something much more like normal hearing.

In order to do this, researchers need to be able to investigate the hair cells outside of the ear. And if they could grow them and watch the hair cells develop, creating such treatments becomes more feasible.

And that's precisely what Heller and his co-investigators - Huawei Lei, Graham Roblin and Hong Liu - set out to do.

With some directed coaxing, they manipulated colonies of mouse embryonic stem cells to grow into inner ear hair cells in a dish.

The cells showed all of the markers of hair cells - and even began to physically resemble tiny hair cells under the right conditions.

Next, the transplant

The researchers' next step was to see if the stem cells could be transplanted into the inner ear of a living creature and do the same thing.

Heller and his colleagues chose to try it out on chicken embryos.

The fact that chicks develop in large, external eggs makes them easy to work with.

"You pop a hole into the egg," find the embryo, and insert the cells, said Heller. "When you're done, you cover the hole with a piece of masking tape."

In addition, "chicken embryos have no immune system to speak of," he said. That means the risk of an embryo rejecting the transplants - especially cells from another species - is greatly reduced.

According to Heller, the mouse stem cells took to the inner ear of the young chicks and showed all the hallmarks of inner ear hair cells.

The cells, he said, also seemed to take better where the inner ear had been damaged.

This made sense to Heller.

The sensory cells of the inner ear are like an exclusive club, he said. "They don't want someone (foreign cells) to intrude."

But if they are injured, the close-knit group becomes less effective, unable to prevent new cells from joining.

Heller's team was able to identify the mouse cells because it had tagged them blue. This meant the hair cells the team observed in the chicks were at least partly of mouse origin.

Transplantation questioned

But that's where the questions begin.

Donna Fekete, a professor of biology at Purdue University, in West Lafayette, Ind., said that although she found the work to be clever, she had a lot of questions.

"First of all, what are the other cells becoming?" she asked, referring to transplanted stem cells that did not become inner ear hair cells.

"They are only interpreting the positive results," she said.

She also expressed concerns about fusion - the process by which the transplanted stem cells fuse with native cells to create hybrids with abnormal genetic characteristics .

A way to test for fusion

Battey, the NIH researcher, expressed concern about this, too. He suggested that Heller and his team design colored markers for chick cells, too, so they could see whether fusion was occurring.

"That'd be the only way to rule it out," he said.

Which isn't to say "that I'm degrading their work," he said. "To have progressed as far as they have is, to me, a major tour de force."

Fekete expressed a bit more skepticism.

"Let's just say that I am cautiously optimistic," she said.

"I don't want to sound like I'm coming down on their work," she said. "I think this is very promising research. It's just that it's in its very early days."

From the Oct. 28, 2003 editions of the Milwaukee Journal Sentinel



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