Success of sensory cell regeneration raises hope for hearing restoration

April 11, 2017
Jian Zuo, Ph.d., and his colleagues induced supporting cells located in the inner ear of adult mice to take on the appearance of immature hair cells and to begin producing some of the signature proteins of hair cells. Credit: Jian Zuo, Ph.D., of St. Jude Children's Research Hospital

In an apparent first, St. Jude Children's Research Hospital investigators have used genetic manipulation to regenerate auditory hair cells in adult mice. The research marks a possible advance in treatment of hearing loss in humans. The study appears today in the journal Cell Reports.

Loss of auditory due to prolonged exposure to loud noise, accidents, illness, aging or medication is a leading cause of hearing loss and long-term disability in adults worldwide. Some childhood cancer survivors are also at risk because of hair cells damage due to certain chemotherapy agents. Treatment has focused on electronic devices like hearing aids or cochlear implants because once lost, human auditory hair cells do not grow back.

"In this study, we looked to Mother Nature for answers and we were rewarded," said corresponding author Jian Zuo, Ph.D., a member of the St. Jude Department of Developmental Neurobiology. "Unlike in humans, auditory hair cells do regenerate in fish and chicken. The process involves down-regulating expression of the p27 and up-regulating the expression of the protein Atoh1. So we tried the same approach in specially bred mice."

By manipulating the same genes, Zuo and his colleagues induced supporting cells located in the inner ear of to take on the appearance of immature hair cells and to begin producing some of the signature proteins of hair cells.

The scientists also identified a genetic pathway for hair cell regeneration and detailed how proteins in that pathway cooperate to foster the process. The pathway includes the proteins GATA3 and POU4F3 along with p27 and ATOH1. In fact, investigators found that POU4F3 alone was sufficient to regenerate hair cells, but that more hair cells were regenerated when both ATOH1 and POU4F3 were involved.

Corresponding author Jian Zuo, Ph.D., a member of the St. Jude Department of Developmental Neurobiology. Credit: St. Jude Children's Research Hospital

"Work in other organs has shown that reprogramming cells is rarely accomplished by manipulating a single factor," Zuo said. "This study suggests that supporting cells in the cochlea are no exception and may benefit from therapies that target the proteins identified in this study."

The findings have implications for a phase 1 clinical trial now underway that uses gene therapy to restart expression of ATOH1 to regenerate hair cells for treatment of .

ATOH1 is a transcription factor necessary for hair cell development. In humans and other mammals, the gene is switched off when the process is complete. In humans, ATOH1 production ceases before birth.

"This study suggests that targeting p27, GATA3 and POU4F3 may enhance the outcome of gene therapy and other approaches that aim to restart ATOH1 expression," Zuo said.

The research also revealed a novel role for p27. The protein is best known as serving as a check on cell proliferation. However, in this study p27 suppressed GATA3 production. Since GATA3 and ATOH1 work together to increase expression of POU4F3, reducing GATA3 levels also reduced expression of POU4F3. When the p27 gene was deleted in mice, GATA3 levels increased along with of POU4F3. Hair cell regeneration increased as well.

"Work continues to identify the other factors, including small molecules, necessary to not only promote the maturation and survival of the newly generated , but also increase their number," Zuo said.

Explore further: Gene therapy for hearing loss: Potential and limitations

Related Stories

Gene therapy for hearing loss: Potential and limitations

May 11, 2012
Regenerating sensory hair cells, which produce electrical signals in response to vibrations within the inner ear, could form the basis for treating age- or trauma-related hearing loss. One way to do this could be with gene ...

New technique generates high volume of sensory cells needed for hearing

February 21, 2017
The loss of tiny, sound-sensing cells in the inner ear, known as "hair cells," is a leading cause of hearing loss, a public health problem affecting at least 5 percent of the world population. Hair cells, which do not regenerate ...

Researchers regenerate sound-sensing cells in the ears of mice with hearing damage

February 20, 2014
One of the major causes of hearing loss in mammals is damage to the sound-sensing hair cells in the inner ear. For years, scientists have thought that these cells are not replaced once they're lost, but new research appearing ...

Study of inner ear development hints at way to restore hearing and balance

October 26, 2015
Loud noise, trauma, infections, plain old aging—many things can destroy hair cells, the delicate sensors of balance and sound within the inner ear. And once these sensors are gone, that's it; the delicate hair cells don't ...

Sensory hair cells regenerated, hearing restored in mammal ear

January 9, 2013
Hearing loss is a significant public health problem affecting close to 50 million people in the United States alone. Sensorineural hearing loss is the most common form and is caused by the loss of sensory hair cells in the ...

Blocking Notch pathway leads to new route to hair cell regeneration to restore hearing

December 22, 2014
Sensory hair cell loss is the major cause of hearing loss and balance disorders. The postnatal mammalian inner ear harbors progenitor cells which have the potential for hair cell regeneration and hearing recovery, but the ...

Recommended for you

Engineered protein treatment found to reduce obesity in mice, rats and primates

October 19, 2017
(Medical Xpress)—A team of researchers with pharmaceutical company Amgen Inc. report that an engineered version of a protein naturally found in the body caused test mice, rats and cynomolgus monkeys to lose weight. In their ...

New procedure enables cultivation of human brain sections in the petri dish

October 19, 2017
Researchers at the University of Tübingen have become the first to keep human brain tissue alive outside the body for several weeks. The researchers, headed by Dr. Niklas Schwarz, Dr. Henner Koch and Dr. Thomas Wuttke at ...

Cancer drug found to offer promising results in treating sepsis in test mice

October 19, 2017
(Medical Xpress)—A combined team of researchers from China and the U.S. has found that a drug commonly used to treat lung cancer in humans offers a degree of protection against sepsis in test mice. In their paper published ...

Tracing cell death pathway points to drug targets for brain damage, kidney injury, asthma

October 19, 2017
University of Pittsburgh scientists are unlocking the complexities of a recently discovered cell death process that plays a key role in health and disease, and new findings link their discovery to asthma, kidney injury and ...

Study reveals key molecular link in major cell growth pathway

October 19, 2017
A team of scientists led by Whitehead Institute has uncovered a surprising molecular link that connects how cells regulate growth with how they sense and make available the nutrients required for growth. Their work, which ...

Inflammation trains the skin to heal faster

October 18, 2017
Scars may fade, but the skin remembers. New research from The Rockefeller University reveals that wounds or other harmful, inflammation-provoking experiences impart long-lasting memories to stem cells residing in the skin, ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

betterexists
not rated yet Apr 11, 2017
SO, Use Priests of ALL Religions for Trials INSTEAD OF Rats/MICE ! THEY WANT WELFARE of Their B.S FellowMenWomen in That Order?

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.