There is no biological cure for deafness—yet. We detect sound using sensory cells sporting microscopic hairlike projections, and when these so-called hair cells deep inside the inner ear are destroyed by illness or loud noise, they are gone forever. Or so scientists thought. A new study finds specific cells in the inner ear of newborn mice that regenerate these sensory cells—even after damage, potentially opening up a way to treat deafness in humans.
Researchers knew that cells in the inner ear below hair cells—known as supporting cells—can become the sensory cells themselves when stimulated by a protein that blocks Notch signaling, which is an important mechanism for cell communication. Albert Edge, a stem cell biologist at Harvard Medical School in Boston, and his colleagues, attempted to identify the exact type of supporting cells that transform into sensory ones and fill in the gaps left by the damaged cells.
The researchers removed the organ of Corti, which is housed within a seashell-shaped cavity called the cochlea and contains sensory hair cells, from newborn mice and kept the cells alive in culture plates. They damaged the hair cells using the antibiotic gentamicin, which destroys its sound-sensing projections. When they examined the organ of Corti under the microscope, they saw that small numbers of hair cells had regenerated on their own. But if they blocked Notch signaling, they saw even more regenerated hair cells, the team reports today in Stem Cell Reports. The number that developed varied, but in the base of cochlea, where the tissue received the most damage, hair cell numbers returned to about 40% of the original. “It’s interesting and encouraging that they are capable of regenerating,” Edge says.
The researchers then tracked which supporting cells turned into hair cells by tagging them with a fluorescent chemical and watching the tissues for at least 4 days. By following the tag, they saw that only cells carrying a protein found in stem cells, called Lgr5, turned into new hair cells. “Knowing about these Lgr5 cells is valuable for us because it gives us a target cell population to study as we try to figure out how to better manipulate them and turn them into hair cells in an adult,” Edge says.
The work contradicts previous studies that found that multiple types of unidentified supporting cells transform into hair cells when Notch signaling is blocked. In these studies, the hair cell growth occurred without any initial damage to the organ of Corti.
The recent study follows a similar paper published earlier this month by developmental neurobiologist Jian Zuo, of St. Jude Children's Research Hospital in Memphis, Tennessee, who damaged sensory cells in live mice. Zuo also saw regeneration of hair cells from supporting cells, but most of the new cells died within 2 weeks. In humans, the organ of Corti matures in the womb, but in mice, the organ continues to mature for the first 10 days of life, so these same findings may not hold true in humans.
Most people suffering from hearing loss are adults, so understanding how older cells turn off their ability to regenerate will be important in turning that ability back on. "We need to focus more into why does this work early [in life], and not later. That will be key," says Alain Dabdoub, a developmental neuroscientist at the University of Toronto in Canada.