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Potential Stem Cell Cure for Hearing Loss Heard Around the World

Case Western Reserve University, April 6, 2007

i-Pod music players are all the rage these days. In fact, you don’t even need to own one to listen. On most days, you can probably walk by a person who is listening to their i-Pod loud enough for you to hear all the lyrics. Jealous? You shouldn’t be since the odds are on your side in this particular situation to keep your hearing intact. The next big epidemic that will concern our younger generation is noise-induced hearing loss according to current studies. And it will be too late to treat by the time the effects show themselves.

Due to the defective development or loss of the cochlea, which are sensory “microphones” inside the ear, individuals lose their hearing. Loud noise, genetic factors, and even certain cancer drugs can damage these hair cells. Individuals face permanent hearing loss since the lost hair cells are not replaced. The development of new therapeutic approaches to hearing loss would be given a significant spark if stem cells from the adult cochlea could be identified.

At Case Western Reserve University School of Medicine, researchers have been able to isolate cochlear stem cells. The team, which was led by National Center for Regenerative Medicine Drs. Robert Miller and Kumar Alagramam, located the stem cells within the inner ear. Due to their expression of certain genes essential for the development of hearing and their proximity to the ear, the cells are prepared to develop into ear-related tissue. The results of the study have been published in Developmental Neuroscience.

"Previous work in our lab with young-adult mouse cochlear tissue showed expression of genes normally found in stem cells and neural progenitors. This led us to hypothesize that cochlea harbors stem cells and neural precursor cells. Our work in collaboration with Miller's lab supports our hypothesis" Dr. Alagramam said.

As the ear develops and ages, the precursor cells ability to regenerate hair cells diminishes over time. But new hair cells could be regenerated by activating the cochlear stem cells. The team’s primary focus is to devise a therapy to do just that.

"Clearly we have miles to go before we reach our end goal, but the exciting part is now we can test compounds that could promote regeneration of hair cells from these precursor cells in vitro, we can study the genes expressed during the transition from stem cells to hair cells, and we can think of developing strategies for cell replacement, i.e. transplanting these cochlear stem cells into the adult cochlea to affect hair cell replacement in the mouse, by extension, in humans" remarked Dr. Alagramam.

Using a panel of stem cell development and hair cell markers, Drs. Miller and Alagramam were able to present evidence of the existence of cochlear stem cells in mouse cochlea by characterizing these cells in terms of neural and hair cell development and confirming the ability to form 'stem cell' spheres in culture. Substantiating the possibility that self-supporting hair cell precursors exist in or can be derived from the postnatal mammalian cochlea is the creation of spheres from early postnatal cochlear tissues and their expression of a wide range of developmental markers unique to hair cells.

The repair of these hair cells is currently impossible since there are no clinical treatments in existence for this purpose. For those over the age of 65 in the United States, 30% have handicapping hearing loss. Before reaching adulthood, one in 500 of those individuals become deaf. Damage to the highly specialized hair cells that the research is focusing on is the culprit in most cases.

Enabling us to hear a whisper or a piano, highly specialized neuroepithelial cells are docked inside the spiral duct of the human cochlea. They are 15,000 strong. Set into vibration by different frequencies of sound, these hair cells differ in length by microscopic amounts. Electrical impulses are sent along the auditory nerve and to the brain when the hairs go into motion; this enables us to hear sound. The hair cells no longer send signals to the brain if they are damaged by sound that is too loud. The hair cells do not regenerate naturally if they are severely damaged and they cannot repair themselves.

The researchers believe these precursor cells can restore normal hearing since they have the potential to regenerate the damaged hair cells. But further research is necessary. In deaf mice mutants with predictable patterns of early hair cell loss and well-established hair cell ablation models, the team has begun studies to explore the use of cochlear stem cells. In the near future, numerous individuals are going to suffer from noise-induced hearing loss. In order to accomplish the goal of developing new therapies for these individuals, this line of research will evaluate the differentiation and in vivo survival of self-renewing cochlear cell populations.


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