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More than 20 years ago, Douglas Cotanche, PhD, then at the Medical University of South Carolina and now affiliated with Children's Hospital Boston, discovered that the hair cells within the chick cochlea were capable of a "significant amount of recovery and regeneration" following acoustic trauma.1 His unexpected discovery began a cascade of research on the question of whether hair cells within the human cochlea could someday achieve the same regenerative results. If and when this happens, many of the causes of hearing loss in humans, from noise to aging, can finally be resolved without the need for hearing aids or cochlear implants.
Although steady progress has been made in understanding the mechanisms underlying hair cell regeneration, human subjects have yet to participate in clinical trials concerned with regrowing hair cells. Such trials may still be years away. Let's look at a sampling of the research in 2008, which moves us ever closer to the goal of restoring hearing in this most natural way.
Summary of Present Knowledge
Dr. Cotanche provides the following concise summary of hair cell regeneration in the abstract of his 2008 article, "Genetic and pharmacological intervention for treatment/prevention of hearing loss," which appeared in the Journal of Communication Disorders:
"Twenty years ago it was first demonstrated that birds could regenerate their cochlear hair cells following noise damage or aminoglycoside treatment. An understanding of how this structural and functional regeneration occurred might lead to the development of therapies for treatment of sensorineural hearing loss in humans..
".Although hair cells in the mammalian cochlea undergo apoptosis [death] in response to noise damage and ototoxic drug treatment, the supporting cells do not possess the ability to undergo regeneration. However, current experiments on genetic manipulation, gene therapy, and stem cell transplantation suggest that regeneration in the mammalian cochlea may eventually be possible and may one day provide a therapeutic tool for hearing loss in humans."2
Genetic Transfer
Scientists at Oregon Health & Science University have successfully produced functional auditory hair cells in the cochlea of the mouse inner ear.3 The "breakthrough" suggests that a new therapy may be developed in the future to successfully treat hearing loss.
John Brigande, PhD, assistant professor of otolaryngology at the Oregon Hearing Research Center, and his colleagues were able to produce hair cells by transferring a key gene on chromosome 4, called Atoh1, into the developing inner ears of mice, tracking its exact location through the use of a green florescent protein (GFP). Through this "glowing" marker, the researchers were able to trace how the inserted genetic material successfully led to hair cell production, resulting in the appearance of more hair cells than are typically located in the ears of early postnatal mice.
"It remains to be determined whether gene transfer into a deaf mouse will lead to the production of healthy cells that enable hearing. However, we have made an important step toward defining an approach that may lead to therapeutic intervention for hearing loss," Dr. Brigande said.
Transplanted Stem Cells
Stem cells are immature cells with the potential for developing into more specialized cells including blood, muscle, nerve, and inner ear hair cells. According to an Italian research team, hearing loss due to cochlear damage may be repaired by transplantation of human umbilical cord hematopoietic stem cells (HSC). They found that a small number migrated to the damaged cochlea and repaired sensory hair cells and neurons.4 For their study, the team used mice in which permanent hearing loss had been induced by intense noise, chemical toxicity, or both.
"Our findings show dramatic repair of damage with surprisingly few human-derived cells having migrated to the cochlea," said Roberto P. Revoltella, MD, PhD, lead author of the study. "A fraction of circulating HSC fused with resident cells, generating hybrids, yet the administration of HSC appears to be correlated with tissue regeneration and repair as the cochlea in non-transplanted mice remained seriously damaged.
According to Dr. Revoltella, their results suggest the possibility of an "emerging strategy for inner ear rehabilitation. providing conditions for the resumption of deafened cochlea."
Transplanted Brain Cells
U.S. scientists believe that lost hair cells may be replaced with stem cells from a particular region of the brain.5 The key cells come from the lining of the lateral ventricle of the brain and share characteristics of the inner ear hair cells. Unlike them, however, they have the ability to reproduce.
The researchers, led by Dongguang Wei, PhD, from the University of California at Davis, believe the brain cells could potentially be transplanted from a person's brain into their ear, where they would take on the role of hair cells and restore hearing. Their conclusions are based on a detailed analysis of the structure, chemistry and role of the brain cells and tests of the theory are already underway in the laboratory.
Bone Marrow Stem Cells
According to the Fars News Agency, Iranian researchers have successfully extracted bone marrow stem cells from rodents and produced in vitro inner ear hair cells.6 "In this 2-year project, researchers cultured and produced inner ear hair cells, a procedure which is not commonly performed in other countries," said research team-leader Mohammed Farhadi.
Farhadi reported that injecting the resultant cells into deaf mice had successfully "tackled" hearing loss in them. He added that this method also reduces the rejection risk as the inner ear cells are produced from the bone marrow stem cells of the deaf individual.
"Exciting Progress"
Greek researchers summarize their view of progress in a 2008 issue of Otology& Neurotology as follows:
"There is an already exciting progress in the fields of sensory cell regeneration and SC [stem cell] research in an attempt to restore hearing or prevent deafness. However, further understanding of the underlying mechanisms of auditory genetics, continuing investigation of the human genome, refinement of the delivering techniques, and specification of the therapeutic strategies have to be developed before functional regeneration of the cochlea can be achieved in clinical practice."7
References
1. Cotanche, DA. (l987). Regeneration of hair cell stereocilliary bundles in the chick cochlea following severe acoustic trauma. Hearing Research, 30(2-3): 181-95.
2. Cotanche DA. (2008). Genetic and pharmacological intervention for treatment/prevention of hearing loss. Journal of Communication Disorders, 41(5): 421-43.
3. Oregon Health & Sciences University (2008, August 30). Treatment for hearing loss? Scientists grow hair cells involved in hearing. ScienceDaily. Accessed online at www.sciencedaily.com/releases/2008/08/080830005613.htm
4. Cell Transplantation: The Regenerative Medicine Journal (2008, September 4). Hearing restoration may be possible with cochlear repair after transplant of human cord blood cells. ScienceDaily. Accessed online at www.sciencedaily.com/releases/2008/09/080903134211.htm
5. Brain cell hope for hearing loss. (2008). BBC News. Accessed online at http://news.bbc.co.uk.go/pr/fr/-/2/hi/health/7770665.stm
6. Iran makes in vitro inner ear hair cells. (2008). Fars News Agency. Accessed online at http://english.farsnews.com/newstext.php?nn=8707291151
7. Viastarakos, PV, Nikolopoulos, TP, Tavoulari, E, Papacharalambous, G, et al. (2008). Sensory cell regeneration and stem cells: what we have already achieved in the management of deafness. Otology & Neurotology, 29(6): 758-68.
Jess Dancer is professor emeritus of audiology at the University of Arkansas at Little Rock. Contact him at jedancer@ualr.edu.
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