Researchers Use Human Embryonic Stem Cells to Restore Hearing

The demonstration in rodents could one day be combined with cochlear implants to treat more people than is currently possible.

Sound effects: Human stem-cell-derived neurons repopulate the inner ear of deaf gerbils. Human cells are labeled green, red, and yellow, where red and yellow mark mature or maturing neurons. Marcelo Rivolta, University of Sheffield

Researchers have restored hearing in deaf rodents using human embryonic stem cells, demonstrating for the first time that these cells can replace missing or damaged neurons in the auditory pathway. The authors suggest that this method could one day be used in combination with cochlear implants. Such an approach would aid more deaf patients than can currently benefit from the bionic prosthetic alone.

Cochlear implants can help patients who have lost or damaged hair cellsthe first sensory cells in the auditory pathwaybut don't work if patients have also lost the neurons that transmit the auditory information to the brain. By filling in this part of the auditory pathway, the new approach could enable doctors to use cochlear implants to treat even those patients who have lost both their hair cells and the signal-transmitting neurons.

Patients can lose these neurons if their hair cells are no longer working or are missing. "Most causes of hearing losswhether it is congenital hearing loss from some sort of genetic defect or acquired hearing loss from chronic noise exposure or powerful antibiotics or chemotherapygenerally those patients have a hair-cell-based hearing loss," says Daniel Lee, a surgeon at the Massachusetts Eye and Ear Infirmary in Boston who performs cochlear implantations. "Over time, after you lose the ability to hear due to hair-cell loss, the neurons get pruned back due to lack of activity," he says.

To address the loss of these cells, Marcelo Rivolta, a sensory-stem-cell biologist at the University of Sheffield in England, and his coauthors devised a method to turn human embryonic stem cells into ear-cell progenitors, cells that can then be transplanted into the inner ear, where they further differentiate into auditory neurons.

The researchers demonstrated that the transplanted cells could transmit sound signals into the brain. They did this by measuring the electrical activity of the neurons in response to sound. While other groups had previously shown that mouse embryonic stem cells can differentiate into these auditory neurons and grow within the inner ear after transplantation, they were unable to demonstrate a functional recovery.

The ultimate goal of stem-cell therapy is to replace both the hair cells and the neurons, says Rivolta, but the procedure is much more difficult for the hair cells. "We are still lacking a surgical technique to deliver the cells in the right place without damaging the ear. Moreover, the cells would need to graft in a perfect arrangement, at a correct angle," he says.

The stem-cell treatment could eventually be combined with cochlear implants to give more deaf patients the ability to hear. But much more work would be required to bring this idea to fruition.

While the study shows the potential of stem cells to replace auditory nerve fibers, says Stefan Heller, who studies hair-cell function and regeneration at the Stanford School of Medicine, the results will be difficult to translate to patients. "It is virtually impossible to diagnose a reduction of auditory nerve fibers in hearing-loss patients." The risk of tumor formation, an issue carried by all potential embryonic stem-cell therapies, are also carried by this treatment, he says.

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Researchers Use Human Embryonic Stem Cells to Restore Hearing