Abstract
Sensory neural hearing loss and vestibular dysfunction have become the most common forms of sensory defects, affecting millions of people worldwide. Developing effective therapies to restore hearing loss is challenging, owing to the limited regenerative capacity of the inner ear hair cells. With recent advances in understanding the developmental biology of mammalian and non-mammalian hair cells a variety of strategies have emerged to restore lost hair cells are being developed. Two predominant strategies have developed to restore hair cells: transfer of genes responsible for hair cell genesis and replacement of missing cells via transfer of stem cells. In this review article, we evaluate the use of several genes involved in hair cell regeneration, the advantages and disadvantages of the different viral vectors employed in inner ear gene delivery and the insights gained from the use of embryonic, adult and induced pluripotent stem cells in generating inner ear hair cells. Understanding the role of genes, vectors and stem cells in therapeutic strategies led us to explore potential solutions to overcome the limitations associated with their use in hair cell regeneration.
Highlights
Hearing loss has become one of the most common disabilities in the United States and can affect almost every age group
We explore how different genes, viral vectors and stem cell sources can be used in conjunction with each other to engineer inner ear hair cells and develop strategies in restoring the function of the inner ear
A critical gene responsible for inner ear development is the Atonal gene—a protein belonging to the basic helix-loop-helix
Summary
Hearing loss has become one of the most common disabilities in the United States and can affect almost every age group. Sensorineural hearing loss (SNHL) involves damage to the cochlea (inner ear sensory hair cells) or the eighth nerve. It is irreversible and in most cases a hearing aid is required. Common causes for SNHL are aging, ototoxic drugs, noise induced trauma, inner ear concussion, and immune disorders [4,5,6]. Hair cell death can occur due to a variety of causes, such as age related deafness (presbycusis), a high dosage of ototoxic drugs (e.g., gentamycin, cisplatin, aminoglycosides), genetic disorders, infectious diseases, or high levels of noise exposure [3,8,9]. We explore how different genes, viral vectors and stem cell sources can be used in conjunction with each other to engineer inner ear hair cells and develop strategies in restoring the function of the inner ear
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