AAAS Session Explores Cochlear Hair Cell Regeneration Research Shows Promise, Limitations for Treatment ASHA News
ASHA News  |   April 01, 2005
AAAS Session Explores Cochlear Hair Cell Regeneration
Author Notes
  • Ellen Uffen, is the managing editor, features, of The ASHA Leader.
    Ellen Uffen, is the managing editor, features, of The ASHA Leader.×
Article Information
Hearing & Speech Perception / ASHA News
ASHA News   |   April 01, 2005
AAAS Session Explores Cochlear Hair Cell Regeneration
The ASHA Leader, April 2005, Vol. 10, 1-21. doi:10.1044/leader.AN2.10052005.1
The ASHA Leader, April 2005, Vol. 10, 1-21. doi:10.1044/leader.AN2.10052005.1
The current state of scientific knowledge about the regeneration of hair cells and neurons in the auditory system was the topic of an ASHA-sponsored session at the annual meeting of the American Association for the Advancement of Science held in Washington, D.C. on Feb. 17–21. “Restoring Damaged Inner Ear Hair Cells and Their Neural Connections” included presentations by scientists Jennifer Stone, Neil Segil, and Steven Green. The work discussed by the panel of presenters, said moderator Brenda Ryals of James Madison University, demonstrated “the basis for both the promise and limitations involved in treating hearing and balance disorders through a regenerative approach.”
Avian Studies
Stone, of the University of Washington Medical School and Virginia Merrill Bloedel Hearing Research Institute, set the stage with her discussion of “Hair Cell Regeneration in Non-Mammalian Vertebrates.” She explained that hair cells, “highly specialized mechanotransducers located in the inner ear of many vertebrates, which are critical for hearing function,” are highly sensitive to certain toxins, loud or prolonged noise, and changes in the inner ear associated with aging. Once human hair cells are lost, they are not replaced and the decrease in hair cells leads to irreversible auditory problems.
It has been known for 50 years that hair cells can be regenerated in cold-blooded vertebrates. During the past 15 years, however, said Stone, based on evidence from avian studies, “we have begun to understand the extent to which hair cell regeneration is feasible in warm-blooded vertebrates such as ourselves.”
Stone went on to discuss the hair cell regenerative process in birds, which she said could be broken into three phases, cell cycle re-entry and exit, cell fate determination, and cellular maturation. “Studies of the avian auditory epithelium have elucidated several of the cellular processes involved in hair cell regeneration,” Stone said, adding that “gene expression analyses are beginning to uncover potential key molecular players in these processes.” The next step, which Stone acknowledged to be difficult, is to test molecular candidates to determine which ones are “necessary and/or sufficient” for hair cell regeneration. Parallel studies in mammals, it is hoped, will enable comparison between the two animal groups leading to knowledge of why birds are capable of “such a robust regenerative response to hair cell loss, while humans are not.”
Mechanisms of Embryogenesis
Neil Segil of the House Ear Institute spoke on “Controlling Cell Division During Development and Regeneration of the Mammalian Inner Ear.” Although sensory hair cell loss is the leading cause of deafness in humans and the mammalian cochlea cannot regenerate its complement of hair cells, said Segil, hair-cell regeneration does occur in non-mammalian vertebrates and leads to the restoration of hearing.
Such regeneration happens, said Segil, “because when hair cells are lost or damaged in these animals, the surrounding supporting cells begin to divide, and are able to subsequently trans-differentiate into new hair cells.” However, when mammalian cochlear supporting cells exit the cell cycle during embryogenesis, they normally never divide again, even if hair cells die.
To better understand the failure of mammalian cochlear hair cell regeneration, Segil studied the molecular mechanisms underlying cell division control and hair cell differentiation, both during embryogenesis and at early postnatal times. He divided his talk into three parts, first discussing the mechanisms that coordinate the embryonic cell cycle with cell differentiation in the organ of Corti, which is responsible for producing the correct number of sensory cells in the mature inner ear.
He discussed how both hair cells and supporting cells “maintain their normally non-dividing state for the life of the animal, since the inability to overcome this state when hair cells die may be a primary cause of the failure of mammalian hair cell regeneration.” Segil added that these mechanisms may also play a role in hair cell sensitivity to ototoxic agents such as antibiotics and chemotherapy agents. Finally, Segil discussed recent in vitro results indicating that “some mammalian supporting cells do indeed retain the capacity to divide and act as hair cell progenitors, making them an important target for continued efforts to induce hair cell regeneration therapeutically.”
Spiral Ganglion Neurons and Peripheral Axons
The final presenter, Steven Green of the University of Iowa, discussed “Control of Spiral Ganglion Neuronal Survival and Axon Growth.” He noted that hair cells of the cochlea are “the auditory sensory cells and convert vibrations of sound into the electrical and chemical language of the nervous system,” but do not connect directly to the brain. “This is the job of about 30,000 nerve cells found in the cochlea,” the cell bodies of which are within an elongated nerve cluster-or ganglion-that runs along the inside of the spiral of the cochlea. “Hence, the ganglion is called the spiral ganglion and the nerve cells are the spiral ganglion neurons (SGNs).” Each of these neurons extends a short, peripheral axon to contact a hair cell. When hair cells die, SGNs soon lose this peripheral axon and die.
Currently, the most effective treatment for sensorineural hearing loss, caused by the loss of hair cells, is the use of cochlear implants. The device involves surgical implantation into the cochlea of an electrode array that directly stimulates the SGNs in response to sound. The implant, however, is limited in the amount of information it can supply. “Future treatment for sensorineural deafness,” said Green, “requires long-term protection of SGNs from death-as loss of SGNs would make an implant ineffective-and an increase in the amount and precision of information supplied to the SGNs.”
Green added that these goals require interventions directed at the SGNs in combination with hair cell regeneration and improvements in cochlear implant design. In addition to SGN survival, regrowth of the peripheral axon is also important “because it is necessary for contact with regenerating hair cells and its presence could allow improvements in precision of the information supplied by implanted electrode arrays.”
Green’s research has focused on intracellular regulatory mechanisms relevant to electrical stimulation or membrane depolarization. Using cultured SGNs, he and colleagues have identified the “intracellular signaling pathways that mediate the prosurvival effect of membrane depolarization” and, further, “have determined the subcellular location at which they act and some of their key targets.” Green’s work has also shown that “some intracellular signals activated by membrane depolarization adversely affect axonal growth” and he is currently investigating how these effects might be circumvented.
The AAAS program was organized by Sharon Moss, ASHA’s director of Research Resources and Advocacy; Patrick Feeney of the University of Washington; and Ryals, James Madison University, Harrisonburg, VA.
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April 2005
Volume 10, Issue 5