A Stem Cell-Seeded Nanofibrous Scaffold for Auditory Nerve Replacement
Annual rept. 30 Sep 2012-29 Sep 2013
MICHIGAN UNIV ANN ARBOR
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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.
- Anatomy and Physiology
- Medicine and Medical Research