Human Inner Ear Organoids as an in Vitro Model for Hearing Therapy Development
Abstract
Profound hearing loss is one of the most common service-connected disabilities among active duty military members and Veterans, affecting more than 10% among all Veterans. Hearing loss is caused primarily by loss of sound-sensing cells, called hair cells, in the inner ear. Human hair cells are vulnerable to damage by loud noise, toxic drugs, or aging, but no treatment options are currently available to replace these damaged or lost hair cells. Military personnel are particularly at high risk for being exposed to loud noise in combat and other occupational environments, such as explosions, loud vehicles, and jet engines. Hearing loss in active military personnel impairs tactical performance and increases risk of injury from decreased situational awareness. In addition, Veterans with hearing loss experience significantly reduced quality of life, since they frequently face economic hardships, experience social isolation and depression, and, in severe cases, are unable to perform basic daily routines. The primary goal of this study is to develop human dish-grown, three-dimensional inner ear tissues, so called "human inner ear organoids," which mimic the structure and function of native human inner ear tissues. We will focus on establishing cochlear tissues containing sound-sensing receptors and neurons that transmit hearing sensation to the brain. We will also aim at establishing dish-grown cochlear tissues containing dying receptors cells. These 3D organ replicas will be used to test whether a candidate compound with proven ability to regulate gene transcription can promote hair cell regeneration in dish-grown cochlear tissues. Human 3D cochlear organoids will offer unprecedented opportunities to develop and test new hearing restoration therapies, as knowledge gained from a human model system is readily applicable to human hearing impairments. Beyond the need for regenerative therapies, our model can also be used to identify drugs that protect sound-sensing receptor cells from loud noise and chemical insult. For each potential therapy, an in vitro assay allowing the rapid screening of drug candidates could expedite discovery and preclinical testing. Successful establishment of biological hearing restoration therapy would have tremendous positive effects on the well-being of military service personnel and Veterans. For example, Soldiers with restored hearing would be able to better understand the surrounding environment, including auditory cues, warnings, and signals, avoid life-threatening circumstances, and successfully accomplish the military mission. The therapy would also benefit military Veterans, who would more easily find employment, integrate into society, and live independently, thereby reducing the burden of their family members. Since nearly 1 million Veterans are currently receiving compensation for hearing problems, the hearing restoration therapy would also significantly reduce the costs of VA disability payments.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810062
Entities
People
- Eri Hashino
Organizations
- Indiana University – Purdue University Indianapolis
- United States Army