One class of the numerous forms of age-related deafness is caused by loss of hair cells in the inner ear. These cells are a necessary part of the chain of systems that leads from sound outside the body to signals passing along nerves into the brain for interpretation. As these hair cells are lost, so is hearing capacity. A range of efforts to reverse this loss are underway at various stages of development, such as reprogramming a cell sample into patient-matched hair cells, or, as in this case, finding ways to provoke regeneration in situ, changing cellular behavior so that they rebuild where they would normally not do so.
Within the inner ear, thousands of hair cells detect sound waves and translate them into nerve signals. Each of us is born with about 15,000 hair cells per ear, and once damaged, these cells cannot regrow. Noise exposure, aging, and some antibiotics and chemotherapy drugs can lead to hair cell death. In some animals, those cells naturally regenerate, but not in humans. However, researchers have now discovered a combination of drugs that expands the population of progenitor cells (also called supporting cells) in the ear and induces them to become hair cells, offering a potential new way to treat hearing loss.
The research team began investigating the possibility of regenerating hair cells during an earlier study on cells of the intestinal lining. In that study, researchers reported that they could generate large quantities of immature intestinal cells and then stimulate them to differentiate, by exposing them to certain molecules. During that study, the team became aware that cells that provide structural support in the cochlea of the ear express some of the same surface proteins as intestinal stem cells. The researchers decided to explore whether the same approach would work in those supporting cells.
They exposed cells from a mouse cochlea, grown in a lab dish, to molecules that stimulate the Wnt pathway, which makes the cells multiply rapidly. At the same time, to prevent the cells from differentiating too soon, the researchers also exposed the cells to molecules that activate another signaling pathway known as Notch. Once they had a large pool of immature progenitor cells, the researchers added another set of molecules that provoked the cells to differentiate into mature hair cells. This procedure generates about 60 times more mature hair cells than the technique that had previously worked the best, which uses growth factors to induce the supporting cochlea cells to become hair cells without first expanding the population.
The researchers found that their new approach also worked in an intact mouse cochlea removed from the body. In that experiment, the researchers did not need to add the second set of drugs because once the progenitor cells were formed, they were naturally exposed to signals that stimulated them to become mature hair cells. “We only need to promote the proliferation of these supporting cells, and then the natural signaling cascade that exists in the body will drive a portion of those cells to become hair cells.” Because this treatment involves a simple drug exposure, the researchers believe it could be easy to administer it to human patients. They envision that the drugs could be injected into the middle ear, from which they would diffuse across a membrane into the inner ear.