Reprogramming the inner ear to treat hearing loss

A research team led by Massachusetts Eye and Ear has reported a new strategy to induce cell division in the mature inner ear — a breakthrough that may bring scientists a step closer to developing treatments that regrow the missing cells that cause hearing loss.

Hair cells are the specialised inner-ear cells responsible for the transduction of sound-evoked mechanical vibrations into electrical signals that are then relayed to the brain. A number of genetic and environmental factors, including overexposure to loud sounds and ageing, destroy these key cells in the hearing system, leading to permanent hearing loss — a condition for which there are currently no pharmaceutical treatments available.

Previous research has shown that, in the newborn mouse inner ear, cells can be induced to divide and regenerate hair cells after damage. However, in fully mature ears, the capacity for cell division is lost and hair cell regeneration does not occur. In humans, even a newborn inner ear is fully mature. Thus, Dr Zheng-Yi Chen and colleagues at Massachusetts Eye and Ear said that in order to develop new treatments for human hearing loss, “it is essential to demonstrate that cell division and hair cell regeneration can be achieved in a mature mammalian inner ear”.

Dr Chen’s laboratory used a reprogramming approach by activating two molecular signals, Myc and Notch, in the adult ear. They found that mature inner ear cells can be induced to divide. Importantly, some of the new cells developed characteristics of hair cells, including the presence of the transduction channels that carry out the mechanical to electrical conversion, and the ability to form connections with auditory neurons — both of which are essential to hearing.

“Our work revealed that reprogramming is achieved by reactivation of early inner ear developmental genes so that the mature inner ear regains neonatal properties, which enables them to redivide and regenerate,” Dr Chen explained.

The proof-of-concept study, published in the journal Nature Communications and claimed to be the first of its kind, may therefore provide an approach to the regeneration of sensory hair cells and other important inner ear cell types in people with hearing loss. As noted by Dr Chen, “These findings of renewed proliferation and hair cell generation in a fully mature inner ear lay the foundation for the application of reprogramming and hair cell regeneration.

“The most significant aspect of the current study is the fact that [a] fully mature mammalian inner ear still retains the capacity to divide and regenerate if it is sufficiently reprogrammed, which removes a fundamental barrier that has prevented the inner ear regeneration necessary for hearing restoration.”

Dr Chen’s laboratory is now working to discover additional drug-like molecules to achieve cell division and hair cell regeneration in the mature inner ear and in large animal models, including pigs. He said, “We hope that our research can serve as a model for regeneration of other tissues with similar properties that are unable to regrow cells, such as in the retina and the central nervous system.”

Image credit: ©stock.adobe.com/au/cristalov

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