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Investigating ways to re-programme supporting cells in the adult inner ear to re-grow lost hair cells

This is a Discovery Research Grant awarded to Professor Angelika Doetzlhofer at Johns Hopkins University, USA, in 2020. 

Background 

Sound-sensing cells, called hair cells, are critical for our ability to hear. Hair cells are located within a snail shell-shaped structure inside the inner ear, known as the cochlea. They convert sound waves in the air into electrical signals that are sent to our brain to be processed as the sounds we perceive.

Hair cells are formed from a group of cells called precursors (hair cell precursors) before we are born. Once all hair cells have formed, there are no hair cell precursors left to replenish lost or damaged hair cells. This is why the majority of hearing loss in people is permanent.  

Loss or damage to hair cells is a leading cause of hearing loss and deafness in people.

Causes of damage to hair cells can include:

  • excessive noise
  • ageing
  • certain medications
  • and viral infections.

Current treatments for hearing loss are limited to devices such as hearing aids or cochlear implants, which benefit many, but do not restore natural hearing.  

Unlike humans and other mammals, birds can replace their hair cells when they become damaged, thus restoring their hearing. In birds, new hair cells develop from their neighbouring supporting cells (so-called as they provide both physical and chemical support to hair cells). In response to hair cell damage, supporting cells in birds acquire features similar to hair cell precursors, allowing them to replace the lost hair cells.   

Aims 

The researchers will investigate if it’s possible to activate similar precursor-like features in supporting cells taken from adult mice.

To do this, they’ll activate a protein called LIN28B in the supporting cells. LIN28B plays an important role in hair cell precursors and allows hair cells to regenerate in young mice (mice develop hearing several days after they are born, and lose the ability to regenerate hair cells after this time).

The researchers will also test whether increasing metabolism in adult supporting cells will improve their ability to regenerate hair cells. Metabolism is all the chemical reactions that produce energy and basic components in the cells of our body, needed to stay alive, grow and reproduce. Stem cells and precursor cells have a specialised metabolism that supports the energy-demanding process of tissue and cell regeneration.   

The researchers will make use of a new technology, called organoid culture, which involves growing a miniature organ from a mixture of cells in a dish. Using this new technology, the researchers will investigate whether they can find a way to re-activate the ability of supporting cells from adult mice to regenerate hair cells.  

Benefit 

If the researchers are successful, their work could be the first step towards a new treatment to restore lost hair cells, and therefore hearing, in people.