A Stem Cell-Seeded Nanofibrous Scaffold for Auditory Nerve Replacement
Abstract
The chief aim of our study is restoration of hearing by regeneration of peripheral auditory neurons. The study takes a systematic approach in three objectives aiming to push human stem cells toward an auditory neural fate, embed the cells on a functionalized scaffold, and implant the device in a deafened animal model. In the first year of the project grant, we have addressed three key tasks: (1) derivation of sensory neurons from human pluripotent stem cells (hPSCs), (2) development of implantable nanofibrous substrates, and (3) optimization of the deafness model. In contrast to prior experiments in mouse embryonic stem cells, generation of sensory neurons simply by overexpression of neurogenin-1 in human embryonic stem cells was inefficient. As a result, we have established a small molecule programming strategy for producing sensory glutamatergic neurons that express otic transcriptional programs. These methods will be combined with neurogenin-1 overexpression to optimize derivation of auditory-like neurons. In addition, we developed novel methods for coiling a nanofiber scaffold to maintain the auditory nerve topology and establishing ouabain as an effective chemical tool for destroying endogenous auditory neurons in guinea pigs.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2013
- Accession Number
- ADA595089
Entities
People
- R. K. Duncan
Organizations
- University of Michigan