Stem cells restore hearing in deaf gerbils, 1st step to human tests
This undated photo provided by Nature shows cells in the cochlea of deaf gerbils. The yellow ones are nerve cells derived from human embryonic cells. (AP Photo/Nature, University of Sheffield, Marcelo Rivolta)
Published Wednesday, September 12, 2012 1:49PM EDT
Last Updated Wednesday, September 12, 2012 6:02PM EDT
TORONTO -- Researchers have restored the ability to hear in deaf gerbils using implanted human stem cells, achieving what they call a first step in potentially overcoming some causes of hearing loss in people.
While more study is needed to ensure the technique is safe for humans, principal researcher Dr. Marcelo Rivolta of the University of Sheffield said the work shows that stem cells can indeed regenerate nerve cells needed for hearing.
"It is early days, but we believe this is a substantial step forward because what we have here is the proof of concept that we can use human stem cells derived from human embryonic stem cells to repair the ear," Rivolta said from Sheffield, England.
The researchers, who describe their work in a paper published Wednesday in the journal Nature, began by using a chemical to destroy inner-ear mechanisms to render the gerbils deaf.
Gerbils, long-tailed rodents that range in length from 15 to 30 centimetres and live three to four years, have hearing that more closely approximates that of humans, compared with laboratory rats or mice.
Rivolta's team manipulated human embryonic stem cells -- taken from a cell line approved for use in research -- to create "otic progenitor" cells.
Embryonic stem cells give rise to virtually all tissue types in the body, from the various organs to neurons to skin. Progenitor cells generated from stem cells can differentiate into specific kinds of cells -- in this case, cells with the same properties as hair cells and auditory neurons, both critical for sensing sound.
Hair cells, located in the spiral-shaped cochlea in the inner ear, amplify and transform sound vibrations into electrical signals, which are then relayed via the auditory nerve to the brainstem.
While the researchers were able to surgically implant otic progenitor cells to repair the auditory nerve in the gerbils, hair cells are more challenging to deal with, said Rivolta. "We don't have a very good surgical technique to deliver the cells into the specific place that we need to."
Damage to hair cells -- which can be caused by genetic disorders, prolonged exposure to high-decibel noise and infections like bacterial meningitis -- can lead to partial or profound hearing loss.
Such hearing loss can be partially overcome by a cochlear implant, a small electronic device that bypasses damaged portions of the ear and transfers sound signals by directly stimulating the auditory nerve.
"You can replace the hair cells with the cochlear implant, but the cochlear implant will work very poorly or not work at all if you don't have the nerve," said Rivolta, explaining that the idea would be to regenerate the auditory nerve with stem cells and combine that therapy with cochlear implants.
In the gerbils, the researchers tested the animals' ability to hear following stem cell treatment using a method called auditory brainstem response, or ABR, in which electrodes on the skull pick up electrical signals.
"What this method does is if you put sound into the ear canal, if the brain can hear that sound, it will produce an electrical wave. So it's a way of seeing that the pathways are reconnected and functionally active," he said.
ABR testing showed the difference in the gerbils' hearing was substantial.
"To put the quantification in context, if it were a human, it would mean going from not being able to hear a truck on the road to being able to hear speech in a normal room."
Rivolta predicts that trials to test the stem cell therapy in people could begin within a few years, as long as expanded animal testing continues to show promise.
While researchers kept track of the gerbils' progress for about 10 weeks after treatment, Rivolta said the next studies would follow the animals for up to 15 weeks to see if any adverse effects show up.
That's because embryonic stem cells -- which by their very nature are genetically programmed to give rise to many kinds of cells -- have been known to produce tumours in experimental animal models.
Although Rivolta believes tumour formation won't be an issue with the otic progenitor cells, he said safety has to be the first priority before human trials could begin.
"In the current experiments, we haven't seen any problems. But it's not enough. We need to follow it for longer."