Stem Cell Regeneration of Human Spiral Ganglion Neurons Toward Hearing Restoration
Abstract
Hearing loss is a major clinical complaint of military personnel exposed to loud noise known to damage cochlear hair cells and auditory neurons. Our long-term goal is to mitigate this damage through "next-generation" cochlear implants (CIs) that incorporate transplanted human stem cells guided to become new, functional auditory neurons. By combining clinically proven CI methodologies with developing stem-cell-based neural replacement strategies, we seek to achieve large CI performance gains by establishing a new intracochlear neural network to improve CI-neuron connectivity, using the CI to stimulate this network. Our results in Aim 1 allowed us to develop effective means of transplanting stem-cell-derived spiral ganglion neurons (SGNs) into the scala tympani. Our comparisons between a volume flow system and a pressure regulation system for transferring stem cell-derived otic neuronal progenitors (ONP) spheroids and organoids demonstrated that a pressure regulation system resulted in fewer cell death, milder deformities. Our significant findings indicate that hESC-derived 3-D aggregates maintained the molecular and functional characteristics similar to those of otic ONP cells, which are upstream in the SGN lineage. Our results in aim 2 demonstrated that the transplanted stem cell-derived ONP spheroids survived and neuronally differentiated into otic neuronal lineages in vivo. They extended neurites toward the cochlea's bony wall 90 days after the transplantation without the use of immunosuppressant medication.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2020
- Accession Number
- AD1119049
Entities
People
- Akihiro J Matsuoka
Organizations
- Northwestern University