Many of the 275 million people worldwide with moderate-to-profound hearing loss have it because of a faulty link between the inner ear and the brain.
Using gerbils and human embryonic stem cells, Rivolta and colleagues describe how they repaired an important part of that link: the auditory nerve.
â€œWe have the proof of concept that we can use human embryonic stem cells to repair the damaged ear,â€ Rivolta told Nature News.
As well as proving that stem cells can repair damaged hearing, the researchers hope the breakthrough will lead to new treatments.
â€œMore work needs to be done, but now we know itâ€™s possible,â€ said Rivolta.
For their study, he and his colleagues developed a way to turn human embryonic stem cells into ear cells and then transplanted them into deaf gerbils.
The model of hearing loss they treated in the gerbils is similar to auditory neuropathy in humans, where damage to the cochlear nerve (also known as auditory or acoustic nerve) disrupts or prevents sound signals picked up by the cochlea in the inner ear from reaching the brain.
The problem lies mainly with the neurons or nerve cells connecting the brain to the inner-ear hair cells that translate sound into electrical signals.
People with this form of hearing loss are usually born with it, and some cases are known to be caused by faulty genes that have already been identified.
But there is also increasing evidence that auditory neuropathy can be caused by jaundice at birth and other environmental factors such as exposure to noise can also be risk factors.
Rivolta has spent the last ten years developing a way to differentiate human embryonic stem cells into auditory neurons and hair cells.
For this study, the team treated stem cells with two types of fibroblast growth factor, FGF3 and FGF10. This produced two types of primordial sensory cell: otic epithelial progenitors (OEPs) which are like hair cells, and otic neural progenitors (ONPs) which are like neurons.
They then transplanted only the ONPs into the ears of gerbils treated with ouabain, a chemical that damages auditory nerves, but not hair cells.
Ten weeks later, some of the transplanted cells had grown projections that connected to the brain stem.
The researchers used a method called ABR (auditory brainstem evoked responses) to measure how well the brain detects an electrical signal after sound stimulation.
Four weeks after transplantation, the average overall improvement in hearing (functional recovery) was 46%.
â€œThe responses of the treated animals were substantially better than those untreated, although the range of improvement was broad. Some subjects did very well, while in others recovery was poor,â€ Rivalto told the press.
Step Forward Likely to Prompt Further Studies
Rivolta said he and his team believe the study is a big step forward, because it shows they now have a way to make human cochlear sensory cells for use in new drugs and treatments, and to study the function of genes.
He said more research is now needed, for example, to understand the long term implications of such a treatment and its safety.
â€œMoreover, while in auditory neuropathy patients that retain their hair cells the sole application of stem cells could be beneficial; those with more comprehensive damage may need a cochlear implant to compensate for the hair cell deficit. In these patients it is possible that stem cells should be administered in combination with a cochlear implant. It is therefore important to explore this interaction,â€ he explained.
Rivoltaâ€™s group is not the first to differentiate stem cells into auditory nerve cells, but this is the first report of transplanted cells restoring hearing in animals.
Richard Altschuler, a developmental biologist at the Kresge Hearing Research Institute at the University of Michigan in Ann Arbor, is among those who believe the study is a breakthrough that will now prompt further research.
â€œResearch has been stymied by reviewers wanting evidence that stem cells can connect the inner ear to the central nervous system,â€ he told NatureNews.
Dr Ralph Holme, Head of Biomedical Research for the UK charity Action on Hearing Loss (formerly known as the Royal National Institute for Deaf People, RNID), describes the breakthrough as â€œtremendously encouragingâ€, raising the real hope that one day it will be possible to fix the actual cause of some types of hearing loss.
â€œFor the millions of people for whom hearing loss is eroding their quality of life, this canâ€™t come soon enough,â€ says Holme.
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