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Research breakthrough in hair cell regeneration

Researchers in the US recently discovered a way to ‘re-programme’ inner ear cells to produce cells similar to the sound-sensing hair cells in adult mice. This is an important step forward in research to develop treatments for hearing loss, as cells in the adult inner ear do not naturally replace themselves when they are damaged.

The goal of many hearing researchers is to find ways to restore hearing once it’s been lost. Hearing loss can be caused by a number of factors – exposure to harmful levels of loud noise, having to take medicines that damage the cells of the inner ear as a side effect, and ageing, to name a few. The underlying cause is often damage to hair cells, the cells in the inner ear that detect sound. Once these cells are lost, at least in people, they don’t re-grow and so the ear is no longer able to respond to sound – hearing loss is the result.

Image showing cells of the inner ear

Researchers are therefore focussed on finding ways to re-grow these cells, to restore hearing. But while loss of these hair cells in mammals like us is permanent, other animals, like birds and fish, can replace them when they’re damaged. In these animals, other cells in the inner ear, called supporting cells, replicate themselves, and some of those new cells turn into hair cells, replacing the lost ones. The hearing loss isn’t permanent. Even some mammals, like mice, can do this to some extent when they’re very young, although the ability is rapidly lost with age. But adult, mature hair cells do not re-grow in mammals – once they’re gone, they’re gone.

Hair cell regeneration – a treatment for hearing loss?

So researchers working in hair cell regeneration are trying to find ways to switch this ability back on in the human inner ear. We already know that a gene called ATOH1 is crucial for the formation of hair cells. There are a number of treatments in development that aim to switch this gene back on in people with hearing loss, to re-grow their hair cells and hopefully restore their hearing.

But one problem is that supporting cells in the human inner ear don’t naturally replicate themselves following damage. Using ATOH1 to turn existing supporting cells into hair cells without replacing them therefore means the inner ear is still missing vital cells. What’s really needed is a way to induce supporting cells to both replicate and turn into hair cells, just as happens in birds and fish.

‘Re-programming’ supporting cells

We also know from studies in zebrafish that two genes in particular are involved in replacing their lost hair cells. Myc is involved in proliferation – that is, cells replicating themselves – and Notch1 is important in inner ear development. Specifically, it’s needed for correct formation of the region that will ultimately detect sound, including the hair cells and supporting cells.

The research team at Harvard Medical School investigated whether these two genes, along with Atoh1 (the mouse version of the human ATOH1 gene), could induce hair cell regeneration in the adult mouse inner ear. They developed systems to allow them to control the activity of these genes, switching them on and off at will. They showed that transiently activating Myc and Notch1, followed by activating Atoh1, caused supporting cells to proliferate and turn into cells resembling hair cells. These cells had stereocilia (the ‘hairs’ that give hair cells their name). The protein channels in those hairs that are responsible for detecting sounds and sending signals to the brain also appeared to work correctly.

What this means

These findings are the first to show that supporting cells can be re-programmed to proliferate and turn into hair cells in the adult mammalian inner ear. More research is now needed to explore this further. We need to determine if these newly-regenerated hair cells can actually restore lost hearing, and develop ways to transfer these findings into people. But while this is an early step in the process, it’s a crucial breakthrough towards developing treatments to regenerate lost hair cells in people, and ultimately restore hearing.

Further information

The original article was published in the journal Nature Communications earlier this month.

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