Replacing lost auditory neurons using inner ear stem cells could be the key to reversing hearing loss, however these rapidly dividing cells could put patients at risk of developing cancer, according to a recent study published in the journal Stem Cell Reports. The researchers involved in the study have identified a way to control how stem cells are differentiated into auditory neurons, potentially mitigating this cancer risk.
“It’s a cautionary tale,” said senior study author Dr. Kelvin Y. Kwan, assistant professor in the Department of Cell Biology and Neuroscience in the School of Arts and Sciences. “People say, ‘we’ll just put stem cells in and we’re going to replace lost neurons.’ We’re saying that ‘yes, we can make neurons,’ but you have other side effects that are unanticipated, such as increased proliferation of stem cells. So, this will guide us toward a better strategy for cell replacement therapies.”
Hearing loss occurs after the sound-converting hair cells in the inner ear die following repeated exposure to noise. Auditory neurons are also damaged in this process and are unable to be regenerated.
“Hearing loss impacts about 15 percent of the American population – probably more,” said Kwan. “Over the years, you don’t realize that you’re not hearing well until you get tested. We’re one of the few labs trying to figure out how to address the hearing loss issue.”
Using cell culture, Kwan and his colleagues were able to convert inner ear stem cells into auditory neurons after overexpressing the NEUROG1 gene. They found that altering the chromatin structure of the gene could have an effect on how the gene is expressed, potentially reducing the incidence of uncontrolled stem cell proliferation and development of cancer.
“Scientists in other fields should be aware that when using this factor, they’ll probably also increase cell proliferation,” said Kwan. “Ideally, we would change the chromatin state before we start overexpressing NEUROG1 and prevent unwanted stem cell proliferation.”
The researchers suggest that the epigenetic state of the NEUROG1 gene could be controlled through the addition of specific compounds. If this technique is eventually optimised for clinical use, it could offer hope to the 48 million Americans who experience some degree of hearing loss.