MGH researchers find way of regenerating cells key to hearing

Finding someday may help treat hearing loss, neurodegenerative disorders

Selectively turning off a protein that controls the growth and division of cells could allow regeneration of the inner ear’s hair cells, which convert sound vibrations into nerve impulses. The discovery by a research team based at Massachusetts General Hospital (MGH) runs counter to current beliefs about these cells and could eventually lead to ways of preventing or treating hearing loss. The report will appear in the journal Science and is receiving early online release on the Science Express website at http://www.sciencexpress.org.

“These findings give us a potential stragegy for hair cell regeneration, which could have enormous implications for the treatment of hearing and balance disorders,” says Zheng-Yi Chen, DPhil, of the MGH Neurology Service, the study’s senior author. “It also shows that cells that have been considered incapable of regeneration – like most nerve cells – can reproduce under the right conditions, which may have applications to neurodegenerative diseases.”

Named for the hair-like projections on their surfaces, hair cells form a ribbon of vibration sensors along the length of the cochlea, the organ of the inner ear that senses sound. Receiving sonic vibrations through the eardrum and bones of the middle ear, hair cells convert them to electrical signals that are carried to the brain by the auditory nerve. Among the earliest structures to form in embryonic development, hair cells are very sensitive to damage from excessive noise, infections or toxins including some medications. Once damaged, hair cells do not naturally regenerate in mammals, and their death accounts for most types of acquired hearing loss.

Cells grow and divide through a process called the cell cycle, and many proteins have been indentified as controllers of the different cell cycle phases. Chen’s group started by carrying out a comprehensive assessment of which genes are active in the developing mouse ear and when the are expressed. The activity of certain genes suggested that the retinoblastoma (Rb) protein, known to suppress the cell cycle, could be important for halting the cell cycle in hair cells. To follow up that observation, the researchers used a genetically modified mouse strain in which Rb was no longer made in the inner ear.

They found that hair cells in the ears of these mice were significantly more numerous than in normal mice at the same stage of development. These additional cells retained the distinctive appearance of hair cells, performed functions characteristic of normal hair cells and appeared fully able to form proper connections with nerve cells. In addition, hair cells in the modified mice made proteins that indicated they were still actively regenerating, while cells in normal animals did not.

The researchers note that these findings will form the basis for the future work aimed at recovery of hearing through hair cell regeneration. In particular, they have to learn to control the presence of Rb for short times, allowing some regeneration but not too much. The genetic basis of hearing and deafness is almost identical in mice and in humans, so a successful mouse model may ultimately translate into therapy in human patients.

“It’s taken over 10 years of work to show that hair cells can regenerate in tissues, and I hope it won’t take another decade to achieve functional regeneration in a living animal,” says Chen. “But my hope and belief is that, if we can do this in mice, we’ll be able to achieve it in people.” Chen is an assistant professor of Neurology at Harvard Medical School (HMS).