Who said hair cells in the ear of mammals can't regenerate?

With the help of gene therapy, an Israeli researcher was able to regenerate hair cells in the ear of adult guinea pigs

Merit Sloin

A new nerve fiber (in green) grows from the auditory nerve towards two new hair cells (in red) created after the gene transplant. Photo: University of Michigan

Direct link to this page: https://www.hayadan.org.il/earnerve.html

The ability to hear is related to the normal structure of special cells in the inner ear, which carry thin hair-like projections on their surface. For genetic reasons or following environmental events such as ear infections, prolonged exposure to loud noise and side effects of certain medications, or during aging, hair cells are destroyed and hearing is impaired to the point of complete deafness. In mammals, including humans, this is an irreversible condition because the hair cells are unable to regenerate. However, in a new study conducted at the University of Michigan in the US, researchers were able to induce the regeneration of hair cells through gene therapy. The study was published last week in the Journal of Neuroscience.

In a normal ear, the vibrations of the sound waves strike the eardrum and from there pass to the fluid inside a cochlear-like structure in the inner ear. As the fluid in the cochlea moves, it causes hairs in the hair cells lining the interior of the cochlea to vibrate. Following this, the hair cell sends a nerve signal that reaches the hearing area of ​​the brain. Different frequencies of sound waves cause hairs to vibrate in different areas of the cochlea, and this is how the distinction between different sounds is made. Destruction of the hair cells or damage to them prevents the appropriate nerve signals from reaching the brain and hearing is impaired.

At the end of the eighties, studies were published that showed that the inability of hair cells in mammals to regenerate does not characterize all living things. It was found that in birds, hair cells regenerate spontaneously - wherever a hair cell is destroyed, a new cell develops, which fills its place. These findings stimulated many research laboratories to try to understand the mechanism of regeneration in birds and to learn from it how to induce cell regeneration in mammals. One of these laboratories was the laboratory of Prof. Yehoash Raphael, an Israeli who directs his research in the Otorhinolaryngology Department at the University of Michigan Medical School.

In the early 1s, genes active in the process of ear development were discovered. One of them, named Math1, belongs to a large family of genes that have been preserved during evolution and have been found in various animals, from flies to humans. MathXNUMX directs the embryonic cells in the ear to develop into hair cells.
Hair cells rest on cells that provide them with mechanical and biochemical support. During embryonic development, hair cells and their supporting cells develop from a common origin: the cells in which the Math1 gene is active develop into hair cells, and cells in which its activity is prevented take on other roles. With the end of embryonic development in mammals, the production of hair cells ceases. Unlike other covering cells in the body, such as cells covering the skin or the digestive tract, the lining tissue of the inner ear, which, as mentioned, consists of hair cells, does not contain stem cells and is therefore unable to regenerate.

"From previous experiments we knew that the support cells in the ear of birds are the cells that create new hair cells, but there was no evidence that this would also work in the auditory system of mammals," says Raphael. "After the Math1 gene was discovered, we decided to test it. When we induced a high activity of the Math1 gene in mature support cells in the cochlea of ​​guinea pigs, we saw that they change their purpose and become hair cells. Following this finding, we decided to develop a technology to introduce the gene into the support cells in the hope that we will succeed in turning them into hair cells." .

Dr. Kohei Kawamoto, who performed the laboratory experiments, used a virus to carry the Math1 gene into the cells. He inserted the gene into the virus and injected the engineered virus into the inner ear fluid of 14 adult guinea pigs. The same move, but without the gene insertion, was done on 12 guinea pigs that were used Control group Starting one month after the gene was inserted, the researchers scanned the inner ear with an electron microscope of the two groups of animals. In the experimental group that received the gene, the researchers noticed new hair cells in areas where these cells are not normally formed. In contrast, no new hair cells were found. "The inner ear is an ideal target for gene therapy because it is closed, but not sealed , and therefore well isolated," says Raphael. "As long as the amount of virus introduced into the ear is small, its spread to other organs is minimal and the risk of toxicity to body systems Others are very low."

One of the surprising results of the experiment was the discovery of thin nerve fibers that grew towards the new cells. "This shows that the new hair cells produce signals that cause the formation of nerve cell extensions, and that these cells apparently respond to the signals," says Raphael. In the next phase of the research, the team will check if the hair cells of the guinea pigs are indeed active and able to transmit signals to the auditory nerves.

"This is just the beginning," says Raphael. "At this point we have the proof of principle showing that through gene therapy with the appropriate gene, the support cells are able to turn into hair cells. The weak link in the meantime is the viral carrier. We expect the development of viral carriers that do not cause side effects, or non-viral carriers that will be able to effectively introduce the genetic load" .

Prof. Raphael and Prof. Keren Avraham, from the Sackler School of Medicine at Tel Aviv University, are trying to apply the new method in mice that are deaf for genetic reasons and in mice that have lost their hearing as a result of aging. "If we succeed in improving hearing in mice, we hope to use the method to cure deafness In humans, especially in the elderly population suffering from hearing loss due to loss of hair cells," Avraham says.

He knew genetic medicine

https://www.hayadan.org.il/BuildaGate4/general2/data_card.php?Cat=~~~546541860~~~25&SiteName=hayadan