# Engineering High-Fidelity Human Cochlear Organoids

> **NIH NIH R01** · INDIANA UNIVERSITY INDIANAPOLIS · 2022 · $672,435

## Abstract

PROJECT SUMMARY
Loss of sensory hair cells and/or innervating neurons in the cochlea causes irreversible hearing loss in
humans. However, progress on research for realizing biological restoration of hearing has been hampered due
to the paucity of human cochlear tissues. My laboratory recently developed a novel organoid system to
generate inner ear sensory epithelia containing functional sensory hair cells from aggregates of human
pluripotent stem cells in 3D culture. While these first-generation organoids are a valuable tool for studying
human inner ear development, they only generate hair cells with structural and functional properties of native
vestibular hair cells and fail to produce any cochlear cell types. Another limitation with our original system is the
lack of central nervous system components. To overcome these limitations, we aim at developing a next-
generation human microphysiological system that more faithfully recapitulates development of the auditory
periphery and brainstem. In Aim 1, we will carry out genetic programming and a small-scale CRISPR screen to
increase the number of outer hair cells arising in cochlear organoids. The identity of derived hair cells will be
validated by single-cell electrophysiology, electron microscopy and single-cell RNA-sequencing. Additionally,
maturation of derived hair cells will be promoted by thyroid hormone treatments. In Aim 2, we will establish
novel human cochlear-hindbrain assembloids and assess afferent neural circuit development in these
assembloids. In Aim 3, we will develop dynamic/tunable hydrogels and test if introducing a spatial gradient of
stiffness in the microenvironment during organoid formation can affect tissue patterning or cellular
differentiation. Spatial gradients of signaling molecules will be also introduced in hydrogels to test if the dorso-
ventral axis formation can be recapitulated during organoid differentiation. The outcome of this study will
provide a paradigm-changing approach for studying normal and pathological development of cochlear hair
cells and their ascending neural circuits.

## Key facts

- **NIH application ID:** 10535013
- **Project number:** 1R01DC020628-01
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Eri Hashino
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $672,435
- **Award type:** 1
- **Project period:** 2022-07-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10535013

## Citation

> US National Institutes of Health, RePORTER application 10535013, Engineering High-Fidelity Human Cochlear Organoids (1R01DC020628-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10535013. Licensed CC0.

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