An In Vitro Model of Developmental Synaptogenesis Using Cocultures of Human Neural Progenitors and Cochlear Explants
Loading...
Date
2013-03
Journal Title
Journal ISSN
Volume Title
Publisher
Mary Ann Liebert Inc Publishers
Abstract
In mammals, the sensory hair cells and auditory neurons do not spontaneously regenerate and their loss results
in permanent hearing impairment. Stem cell therapy is one emerging strategy that is being investigated to
overcome the loss of sensory cells after hearing loss. To successfully replace auditory neurons, stem cell-derived
neurons must be electrically active, capable of organized outgrowth of processes, and of making functional
connections with appropriate tissues. We have developed an in vitro assay to test these parameters using
cocultures of developing cochlear explants together with neural progenitors derived from human embryonic
stem cells (hESCs). We found that these neural progenitors are electrically active and extend their neurites
toward the sensory hair cells in cochlear explants. Importantly, this neurite extension was found to be signifi-
cantly greater when neural progenitors were predifferentiated toward a neural crest-like lineage. When grown in
coculture with hair cells only (denervated cochlear explants), stem cell-derived processes were capable of lo-
cating and growing along the hair cell rows in an en passant-like manner. Many presynaptic terminals (synapsin
1-positive) were observed between hair cells and stem cell-derived processes in vitro. These results suggest that
differentiated hESC-derived neural progenitors may be useful for developing therapies directed at auditory
nerve replacement, including complementing emerging hair cell regeneration therapies.This is a copy of an article published in the Stem Cells and Development Journal © 2013 [copyright Mary Ann Liebert, Inc.]; Stem Cells and Development is available online at: http://online.liebertpub.com.
Description
Keywords
Citation
Nayagam, B. A., Edge, A. S., Needham, K., Hyakumura, T., Leung, J., Nayagam, D. A. X., & Dottori, M. (2013). An In Vitro Model of Developmental Synaptogenesis Using Cocultures of Human Neural Progenitors and Cochlear Explants. Stem Cells and Development, 22(6), 901-912. doi: 10.1089/scd.2012.0082