内耳再生への幹細胞医学の応用

抄録

Recent advances on stem cell biology are remarkable, and open the door for regeneration of various tissues or organs including inner ears. Here we report the potential of application of stem cell biology into therapeutic strategies for the treatment of inner ear diseases, focusing on the potential of embryonic stem (ES) cells. Es cells are pulripotent and have the ability for self-renewal. The targets for regeneration in the inner ear include sensory hair cells and associated neurons. ES cells can differentiate into various types of cells including neurons and hair cells. ES cells are, therefore, good candidates as transplants for cell therapy for inner ears. The methods for neural induction of ES cells have been established. We therefore attempted to investigate the potential of ES cell-derived neurons for regeneration of spiral ganglion neurons (SGNs). In this study, we used the stromal cell-derived inducing activity (SDIA), which can effectively induce neural differentiation of ES cells. We examined the possibility for neural connections between hair cells and ES cellderived neurons using explant culture techniques, and the potential of ES cell-derived neurons for functional restoration of SGNs. The results demonstrated that ES cell-derived neurons elongated their neuritis to hair cells and exhibited expression of synaptophysin, indicating the formation of synaptic connection with hair cells. After transplantation, robust survival of grafted ES cell-derived neurons was identified in the modiolus of cochlea. Grafted cells massively elongated their neurites in the modiolus. In some cases, functional recovery of SGNs was demonstrated by electrically evoked auditory brainstem responses. These findings strongly suggest a high potential of ES cell-derived neurons as transplants for replacement of SGNs.