Inner ear regeneration is the biological process by which the hair cells and supporting cells (i.e. Hensen's cells and Deiters cells) of the ear proliferate (cell proliferation) and regrow after hair cell injury. This process depends on communication between supporting cells and the brain. Because of the volatility of the inner ear's hair cells, regeneration is crucial to the functioning of the inner ear. It is also a limited process, which contributes to the irreversibility of hearing loss in humans and other mammals.
Anatomy
Hair cells Hair cells and supporting cells are both located in the cochlea inside the inner ear. In mammals, hair cells are located in the Organ of Corti and convert energy from sound waves and physical movement into electrical signals. This is accomplished through integrating neurons with hair cells that transmit signals to the auditory nerve. There are three rows of outer hair cells and one row of inner hair cells on the Organ of Corti. 95% of neurons that transmit signals to the auditory nerve are connected to inner hair cells, making inner hair cells mainly responsible for auditory sensory input. While inner hair cells are the sensory receptors, outer hair cells are the efferent receptors and are important in fine-tuning sensory input by contracting and relaxing to alter the tectorial membrane on the surface of the hair cells.
Supporting cells Supporting cells are critical for maintaining inner ear sensory cells. They reside both on the surface and throughout the epithelium of the inner ear, communicating through gap junctions. Supporting cells are critical for maintaining the physical structure of the inner ear, as well as maintaining the environment of the sensory epithelium of the inner ear. Maintaining appropriate ion concentrations and pH in the inner ear epithelium is important for hair cells to initiate action potentials to transmit signals to the brain. Supporting cells are also responsible for removing damaged hair cells from the inner ear.
Hair cells and most supporting cells are ectoderm-derived. The main types of supporting cells are Hensen's cells, Deiters’ cells, Claudius cells, inner phalangeal cells, and inner and outer pillar cells. Hensen's cells, Deiter's cells, and outer hair cells make up the outer tunnel and are mainly responsible for allowing hair cells to function. Hensen's cells are columnar in shape, have many phagosomes in their cytoplasm and contain lipid droplets that correlate with the extent of their innervation. Deiters’ cells are attached to outer hair cells. They have phalanges that extend to create tight junctions with nearby outer hair cells. Because Deiters’ cells interact with outer hair cells, they play a key role in coordinating shifts and mechanical force between outer hair cells.
Loss of hair cells Hair cells are very sensitive and become damaged easily, resulting in cell death. Supporting cells can be damaged but are typically more resilient than hair cells. Hair cells die of old age, acoustic overstimulation and other traumas. Oxotoxin exposure, such as aminoglycoside antibiotics and cisplatin, is also a major contributor to hair cell death. Because mammals have very limited hair cell regeneration, hearing loss is essentially irreversible and therefore a therapeutic target for regeneration. There are also genetic diseases that can cause hair cell death such as Osteogenesis Imperfecta.
Current therapeutics for hair cell loss in humans Because mammals have very limited hair cell regenerative capacity, humans have developed alternative methods of dealing with hearing loss. Hearing aids are devices that sit in the ear and amplify sound, which helps with age-induced partial hair cell loss. Cochlear implants are a more invasive treatment that bypass the hair cells completely by sending electrical signals from the environment straight to the auditory nerve fibers. This is a great option for patients with minimal to nonexistent hair cell activity. The cochlear implant involves a surgically implanted electrode array and an external device that processes sound.
Hair cell regeneration
Anamniotes All studied nonmammalian vertebrates can regenerate inner ear hair cells (mechanoreceptor). This means that lower vertebrates can recover from deafness due to hair cell loss. Hair cell loss triggers supporting cells to re-enter the cell cycle. Mitotic (mitosis) divisions of quiescent supporting cells in the sensory epithelium of the cochlea give rise to both new hair cells and supporting cells. In some cases, proliferating supporting cells directly transdifferentiate into new hair cells, resulting in hearing recovery. Direct transdifferentiation is when neighboring supporting cells convert into hair cells without cell division. Inner ear sensory epithelium is highly conserved (conservation genetics) in all vertebrates. The study of these nonmammalian vertebrates can lead to a better understanding of the mechanism of hair cell regeneration.
Zebrafish The study of hair cell regeneration mechanisms in adult zebrafish may be transferable to inducing hair cell regeneration in mammals. The basic structure and function of the fish's inner ear is similar to that of other vertebrates. Mammals share homologous genes with zebrafish that are known to affect inner ear structure and function. In zebrafish, spontaneous and damage-induced hair cell regeneration has been demonstrated in the inner ear. The Stat3/SOCS3 pathway has been identified as key in promoting hair cell regeneration through stem cell activation, cell division, and differentiation.
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