Abstract

Hearing loss is a sensory deprivation that can affect the quality of life. Currently, only rehabilitation devices such as hearing aids and cochlear implants are used, without a definitive cure. However, in chronic hearing-deprived patients, in whom secondary auditory neural degeneration is expected, a relatively poor rehabilitation prognosis is projected. Stem cell therapy for cochlear neural structures would be an easier and feasible strategy compared with cochlear sensory cells. Considering the highly developed cochlear implantation technology, improving cochlear neural health has significant medical and social effects. Stem cell delivery to Rosenthal's canal in an acutely damaged mouse model has been performed and showed cell survival and the possibility of differentiation. The results of stem cell transplantation in chronic auditory neural hearing loss should be evaluated because neural stem cell replacement therapy for chronic (long-term) sensorineural hearing loss is a major target in clinics. In the present study, we established a mouse model that mimicked chronic auditory neural hearing loss (secondary degeneration of auditory neurons after loss of sensory input). Then, mouse embryonic stem cells (mESCs) were transplanted into the scala tympani and survival and distribution of transplanted cells were compared between the acute and chronic auditory neural hearing loss models induced by ouabain or kanamycin (KM), respectively. The mESC survival was similar to the acute model, and perilymphatic distribution of cell aggregates was more predominant in the chronic model. Lastly, the effects of mESC transplantation on neural signal transduction observed in the cochlear nucleus (CN) were compared and a statistical increase was observed in the chronic model compared with other models. These results indicated that after transplantation, mESCs survived in the cochlea and increased the neural signaling toward the central auditory pathway, even in the chronic (secondary) hearing loss mouse model.

Highlights

  • Hearing loss is a sensory deprivation that can affect the quality of life

  • In mice treated with ouabain and mouse embryonic stem cells (mESCs), hearing improvement was not observed compared with control (Figure 2(b))

  • Compared with the chronic auditory neural hearing loss model, improvement in hearing threshold was not observed (Figure 2(c)). These results showed that mESCs transplanted via the scala tympani did not produce any hearing improvement in the acute or chronic hearing loss model

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Summary

Introduction

Hearing loss is a sensory deprivation that can affect the quality of life. Therapeutic approaches to cure chronic sensorineural hearing loss without a rehabilitation device do not currently exist due to the lack of regenerative function of sensory hair cells in the cochlea. Rehabilitation devices, such as hearing aids and cochlear implants, are used to reduce the degree of hearing loss and increase sound perceptions [2]. Sensory and neural structures are well organized to properly transduce sound. When bypassing the sensory part among these structures, for example, using hearing aids or cochlear implants to augment hearing, maintaining the health of neural hearing structures remains important [3]. In clinics, early rehabilitation is recommended because neural structures

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