1. photograph of large clonal colonies of cochlear progenitor cells formed from single cells and converted into high purity colonies hair cells (magenta) with intricate hair bundles (cyan). Credit: Will McLean, Ph.D.  2. Newly formed cochlear hair cells contain intricate hair bundles with many stereocilia (critical for sensing sound) and other components that are critical for proper function and neural transmission. (Credit: Will McLean)
Researchers discover a drug combination that can regenerate hair cells. Within the inner ear, thousands of hair cells detect sound waves and translate them into nerve signals that allow us to hear speech, music, and other everyday sounds. Damage to these cells is one of the leading causes of hearing loss, which affects 48 million Americans. Each of us is born with about 15,000 hair cells per ear, and once damaged, these cells cannot regrow. However, researchers at MIT, Brigham and Women’s Hospital, and Massachusetts Eye and Ear have now discovered a combination of drugs that expands the population of progenitor cells (supporting cells) in the ear and induces them to become hair cells, offering a potential new way to treat hearing loss.
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. The team began investigating the possibility of regenerating hair cells in an earlier study on cells of the intestinal lining. In that study, published in 2013, Karp, Langer, Yin et al reported they could generate large quantities of immature intestinal cells and then stimulate them to differentiate, when exposed to certain molecules. During that study, the team became aware that cells that provide structural support in the cochlea 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. “We used small molecules to activate the supporting cells so they become proliferative and can generate hair cells,” Yin says. At the same time, to prevent the cells from differentiating too soon, they also exposed the cells to molecules that activate another signaling pathway known as Notch.
Once they had a large pool of immature progenitor cells (~2000X greater than any previously reported), 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.
They 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.
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. This type of injection is commonly performed to treat ear infections. Some of the researchers have started a company called Frequency Therapeutics, which has licensed the MIT/BWH technology and plans to begin testing it in human patients within 18 months. “We hope that our work will allow other scientists to pursue studies of supporting cells and hair cells that have not been possible because such limited quantities of hair cells were available,” Will McLean says. “Researchers who have been eager to conduct experiments on inner ear hair cells will now be able to replicate our work and have huge numbers of them to do all kinds of experiments,” Karp says.
Karp, Langer, and Yin are also working on applying this approach to other types of cells, including types of intestinal cells involved in insulin regulation and control of the gut microbiota.
http://news.mit.edu/2017/drug-treatment-combat-hearing-loss-0221
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