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Vol. LXII, No. 15
July 23, 2010

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NIDCD-Funded Scientists Grow ‘Ear in a Test Tube’

On the front page...

Hair cells, the tiny sensory cells located in the cochlea of the inner ear that turn sound vibrations into electrical signals, are among the most scarce cells in the body. We’re born with fewer than 15,000 of them per ear and they are the only ones we’ll ever have. Unlike birds and fish, humans don’t have the ability to grow new hair cells if some are lost due to disease, drugs or long-term exposure to noise. Unfortunately, the loss of just a thousand is enough to make a noticeable difference in how well we hear.

For years, hearing research has been hindered because scientists have never been able to get their hands on enough hair cells for experimentation in the lab. As a consequence, we know far less about sensory cells in the ear than we do about their equivalents in the eye or the nose, where such cells are plentiful, renewable and easy to extract.


  Dr. Stefan Heller  
  Dr. Stefan Heller  

All of that is about to change. In May, a group of NIDCD-funded researchers led by Dr. Stefan Heller at Stanford University School of Medicine announced that they had developed a system for making what appear to be functional hair cells from stem cells.

The findings, published in the May 14 issue of Cell, bring the scientists closer to achieving two goals. Short-range, their goal is to grow abundant numbers of working hair cells for further research. Long range, they hope to use what they discover to restore the ear’s ability to regenerate hair cells.

“Our dream was to get what a colleague of mine called a ‘bucketload’ of cells,” says Heller. “Now it’s like having an ear in a test tube.”

Heller and his colleagues began to work on the recipe more than 10 years ago, borrowing knowledge gained from other scientists in the field to guide them as they tried to rebuild hair cells in a culture dish. They began with stem cells from mouse embryos, setting up conditions to mimic what they knew about how the inner ear forms during fetal development.

Then they tried various combinations of growth-inducing substances until they found the one that causes the cells to cluster and display hair cell-like characteristics. The key ingredients were chemicals known as fibroblast growth factors, which were shown in previous studies to be intimately involved in inner-ear development.

Hair cells in the inner ear have a complicated structure. They resemble other kinds of epithelial cells (cells that line the cavities and surfaces of structures in the body) but with a twist.

At their tips, hair cells display a spiky bundle of filaments—known as stereocilia—that contain mechanosensitive ion channels that are able to produce electrochemical signals when stimulated by sound vibrations.

Building a hair cell from scratch meant not only replicating its complicated architecture, but also endowing it with the ability to respond electrochemically to sound vibrations.

A year ago, Heller and his team knew they’d hit on the right combination of factors when they looked at a group of cells through a scanning electron microscope and saw some that were intriguingly hair cell-like with recognizable hair cell bundles at their tips. It took another year to establish that the cells were indeed functional. Stimulated by electrodes, the cells generated electrochemical currents that resembled those made by young hair cells.

Hair cells grown from mouse embryonic stem cells display their characteristic stereocilia.

Hair cells grown from mouse embryonic stem cells display their characteristic stereocilia.

What’s left to do is find a way to encourage these newborn hair cells to take on a specific identity. “They know that they’re hair cells,” explains Heller. “They’ve developed a hair bundle and they can convert mechanical stimulation into electrochemical activity, but they still don’t know whether they’re vestibular or cochlear.”

By growing the manufactured cells with real cochlear cells, the researchers are hoping that the baby cells can take direction from the adults and head in a cochlear direction.

With their “ear in a test tube,” Heller and his team also plan to start a series of tests to search for the biochemical basis of the inner ear’s inability to regrow hair cells.

“Since all the other hair cell-bearing organs in the body are able to replace lost hair cells,” explains Heller, “it’s reasonable to assume that the current structures in the inner ear evolved from structures that once had the capacity of self-repair.”

Finding the switch that turns hair cell regeneration on and off could make returning the inner ear’s capacity to grow hair cells as simple as hitting a chemical reset button, although getting there may take some time.

“We’re one step further on a journey,” says Heller. “It will take a while until we reach any kind of clinical relevance. NIHRecord Icon

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