# Replacement of the cochlear sensory epithelium using stem cell-derived inner ear organoids

> **NIH VA I01** · VETERANS HEALTH ADMINISTRATION · 2022 · —

## Abstract

ABSTRACT
Sensorineural hearing loss is highly prevalent in military Veterans, but there is currently no biological treatment
enabling full restoration of the cochlea and hearing perception. Hearing restoration by stem cell therapy holds
great promise. New advances in the generation of inner ear organoids from pluripotent stem cells and our
pioneering efforts to condition the cochlea for receiving foreign cells have paved the way forward. However,
there remain several major obstacles to combining these approaches. Foremost, there is a lack of a coherent
strategy for identifying the right donor cells and tailoring these to the severity of injury in the cochlea. In this
proposal, we are focused on stem cell therapy for the severely damaged cochlea, where extreme or chronic
injury has reduced the organ of Corti to a flat epithelium of stromal cells that have so far proven refractory to
genetic approaches to regeneration. This approach may be the only viable strategy for restoring the full
sensory epithelium in older Veterans with long-term hearing loss. Protocols for developing inner ear organoids
from pluripotent stem cells produce potential donor cells all along the otic developmental trajectory. Notably,
we have developed methods to isolate otic vesicle progenitors from non-otic cells in these cultures, but
maturation of the vesicles into sensory epithelia requires a complex, commercial extracellular matrix for
efficient differentiation in vitro. In this proposal, we test the hypothesis that multipotent otic progenitors will be
required to replace both hair cells and supporting cells in the severely damaged cochlea. The proposal tests
the impact of implanting donor cells at various stages of differentiation and examines the role of the
extracellular matrix in promoting donor cell survival and maturation. Successful completion of these studies will
open new paths toward a viable biological treatment for severe hearing loss.

## Key facts

- **NIH application ID:** 10313468
- **Project number:** 1I01RX003400-01A2
- **Recipient organization:** VETERANS HEALTH ADMINISTRATION
- **Principal Investigator:** ROBERT KEITH DUNCAN
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2022-01-01 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10313468

## Citation

> US National Institutes of Health, RePORTER application 10313468, Replacement of the cochlear sensory epithelium using stem cell-derived inner ear organoids (1I01RX003400-01A2). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10313468. Licensed CC0.

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