As many aging rock stars have learned, hearing loss due to inner ear damage is irreversible. Loud music assaults the cochlea, the snail-shaped organ of the inner ear whose tiny hair cells detect sound vibrations. The cochlea translates these into electrical impulses that nerves carry to the brain. Once destroyed, hair cells don't regenerate.
Researchers at Genentech in South San Francisco now report that they've grown new hair cells in tissue taken from newborn rats' cochleas. The scientists used fresh supplies of a gene, Math1, to promote hair cell growth. Although the researchers studied only cells in laboratory dishes, their findings raise hopes that deafness from inner ear damage might be reversible.
"It's an exciting study," says Thomas R. Van De Water, an otolaryngologist at Albert Einstein College of Medicine in New York. The work is the first to initiate hair cell growth by adding Math1, he says.
In each developing ear in a human fetus, the protein encoded by Math1 induces up to 16,000 cells in the cochlea to grow bundles of tiny filaments. Once this population of cells has appeared, however, Math1 seems to shut down.
Last year, researchers reported that genetically engineered mice lacking Math1 produced no cochlear hair cells, even in the embryonic stage.
To test whether extra copies of Math1 might boost hair cell production, the Genentech researchers exposed cells from rat cochleas to a DNA ring, or plasmid, containing the Math1 gene. Because plasmids can replicate themselves but don't become a permanent part of a cell, researchers highjack them from bacteria to carry genes for a variety of functions.
The researchers jolted the recipient cells with an electric shock or added a fatty coating to the plasmid to facilitate its entry into the cell. To track the plasmids, the researchers engineered the structures to include a gene that encodes green fluorescent protein.
The researchers studied cells taken from a part of the rat cochlea that doesn't normally grow hairs. During 6 to 12 days of observation, the plasmids induced the cells to produce the Math1 protein, which turns on or off other genes in the cell nucleus. This flurry of activity produced hundreds of hair cells, complete with filaments, the researchers report in the June Nature Neuroscience.
Hair cells normally arise from cells in a part of the cochlea called the sensory epithelium. Earlier this year, Van De Water and his colleagues reported using a different protein, a growth factor, to spur hair cell growth in such cells. In the new study, however, the hairs arose from cells taken from a nearby area, the greater epithelial ridge, says study coauthor Wei-Qiang Gao, a neurobiologist at Genentech.
Whether hair cells generated in this part of the cochlea will reverse deafness "is the great big question," says Ruth Anne Eatock, a sensory physiologist at Baylor College of Medicine in Houston. At least, she notes, "these hair cells are not in some remote part of the organ."
The Genentech researchers took cochlear cells from 1-day-old rats. At birth, the cochleas of rats are still quite immature, even though they already have formed most of their hair cells, she says. The greater epithelial ridge "undergoes significant changes after birth," says Eatock.
Gao says that researchers plan to try the experiment on cells taken from older rats.
"We haven't gotten to the point of generating new hair cells in an old ear, but Gao's study is an important step along the way," Eatock says.
The study also suggests that a plasmid might make a useful vehicle for delivering Math1 to cochlear cells because, Gao says, "it will gradually disappear."
On the other hand, he says, if plasmids turn out to be too weak to do the job, he may use viruses to deliver Math1 in animal tests.
Ruth Ann Eatock
Baylor College of Medicine
Department of Physiology
1 Baylor Plaza
Houston, TX 77030
Department of Neuroscience
1 DNA Way
South San Francisco, CA 94080
Thomas R. Van De Water
Albert Einstein College of Medicine
Rose F. Kennedy Center
1410 Pelham Parkway South
Bronx, NY 10461
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