Potential of embryonic stem cell‐derived neurons for synapse formation with auditory hair cells

Abstract

Recent studies have indicated that embryonic stem cells (ESCs) can be a source for the replacement of spiral ganglion neurons (SGNs), auditory primary neurons, and neurite projections from ESC-derived neurons to auditory sensory epithelia. However, the potential of ESC-derived neurons for synapse formation with auditory hair cells (HCs) has not been elucidated. The present study therefore aimed to examine the ability of ESC-derived neurons to form synaptic connections with HCs in vitro. Mouse ESC-derived neural progenitors expressing enhanced green fluorescence protein (EGFP) were cocultured with explants of cochlea sensory epithelia obtained from postnatal day 3 mice. After a 7-day culture, neurites of ESC-derived neurons predominantly elongated toward inner hair cells (IHCs), which play a crucial role in sound transmission to SGNs. Immunohistochemical analyses revealed the expression of synapsin 1 and synaptophysin in the nerve endings of ESC-derived neurons adjacent to IHCs, indicating the formation of synaptic connections. Transmission electron microscopy demonstrated synaptic contacts between nerve endings of ESC-derived neurons and IHCs. The present findings show that ESC-derived neurons can make synaptic connections with IHCs.

Mammalian Cochlear Hair Cell Regeneration and Ribbon Synapse Reformation

“…Cochlear ribbon synapses have limited intrinsic capacity to spontaneously regenerate [86–88]. Prior study reported that when cochleae is damaged in neonatal mice, the HCs spontaneously regenerate from the SCs, but the inner cell marker vesicular glutamate transporter VGlut3 was not detected in these newly regenerated HCs [10].…”

No longer falling on deaf ears: Mechanisms of degeneration and regeneration of cochlear ribbon synapses

“…In vitro and in vivo studies suggest that cochlear ribbon synapses have intrinsic but very limited regenerative capacity (Chen et al, 2012; Kujawa et al, 2009; Lin et al, 2011; Liu et al, 2013; Liu et al, 2014; Maison et al, 2013; Martinez-Monedero et al, 2006; Matsumoto et al, 2008; Shi et al, 2013b; Tong et al, 2013; Wan et al, 2014). Incomplete repair of these structures after insult or during aging could result in cumulative loss of sensory input, leading to hearing difficulty in noisy environment and a delayed onset of permanent hearing loss.…”

Potential of Pluripotent Stem Cells for the Replacement of Inner Ears

“…Furthermore, transplantation of neural progenitors recovered the function of auditory neurons [29]. The evidence that ESC-derived neurons have the potential to make synapse formation with auditory hair cells justifies the strategies of stem cell transplantation for the regeneration of auditory neurons [22,23]. Toward successful replacement of damaged SGNs by ESCs, establishment of SGN-specific cell types from ESCs is important.…”