Reinnervation of hair cells by neural stem cell-derived neurons.

Yasheng Yuan; Yang Wang; Fanglu Chi

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Reinnervation of hair cells by neural stem cell-derived neurons.

Author: Yasheng YUAN ^{1
,

2} ; Yang WANG ³ ; Fanglu CHI ¹ ;
Author Information

1. Department of ENT-Head & Neck Surgery, Eye, Ear, Nose and Throat Hospital, Shanghai 200031, China
2. Shanghai Medical School, FuDan University, Shanghai 210029, China.
3. Department of Anatomy, Shanghai Medical School, FuDan University, Shanghai 210029, China.
Publication Type:Journal Article
MeSH: Animals; Cell Differentiation; drug effects; Cells, Cultured; Coculture Techniques; Epidermal Growth Factor; pharmacology; Fibroblast Growth Factor 2; pharmacology; Hair Cells, Auditory; cytology; drug effects; ultrastructure; Neural Stem Cells; cytology; drug effects; ultrastructure; Neurons; cytology; drug effects; ultrastructure; Rats; Rats, Sprague-Dawley; Synapses; drug effects; metabolism
From: Chinese Medical Journal 2014;127(16):2972-2976
CountryChina
Language:English
Abstract:
BACKGROUNDReplacement of spiral ganglion neurons would be one prioritized step in an attempt to restore sensory neuronal hearing loss. However, the possibility that transplanted neurons could regenerate new synaptic connections to hair cells has not been explored. The objective of this study was to test whether neural stem cell (NSC)-derived neurons can form synaptic connections with hair cells in vitro.
METHODSNSCs were mechanically separated from the hippocampus in SD rat embryos (E12-E14) and cultured in a serum-free medium containing basic fibroblast growth factor and epidermal growth factor. Rat NSCs were co-cultured with explants of cochlea sensory epithelia obtained from postnatal Day 3 rats under transway filter membrane.
RESULTSAt Day 3, the NSCs began to show chemotactic differentiation and grew toward cochlea sensory epithelia. After 9-day co-culture, neurites of NSC-derived neurons predominantly elongated toward hair cells. Immunohistochemical analyses revealed the fibers overlapped with synapsin and hair cells, indicating the formation of new synaptic connections. After 14-day culture, triple staining revealed the fibers overlapped with PSD95 (postsynaptic density) which is juxtaposed with CtBP2 (presynaptic vesicle), indicating the formation of new ribbon synapse.
CONCLUSIONSNSC-derived neurons can make synaptic connections with hair cells and provide a model for studying synaptic plasticity and regeneration. Whether the newly forming synapse is functional merits further electrophysiological study.