Regenerative therapy for vestibular disorders using human induced pluripotent stem cells (iPSCs): neural differentiation of human iPSC-derived neural stem cells after in vitro transplantation into mouse vestibular epithelia

Abstract

Objectives: Vestibular ganglion cells, which convey sense of motion from vestibular hair cells to the brainstem, are known to degenerate with aging and after vestibular neuritis. Thus, regeneration of vestibular ganglion cells is important to aid in the recovery of balance for associated disorders.

Methods: The present study derived hNSCs from induced pluripotent stem cells (iPSCs) and transplanted these cells into mouse utricle tissues. After a 7-day co-culture period, histological and electrophysiological examinations of transplanted hNSCs were performed.

Results: Injected hNSC-derived cells produced elongated axon-like structures within the utricle tissue that made contact with vestibular hair cells. A proportion of hNSC-derived cells showed spontaneous firing activities, similar to those observed in cultured mouse vestibular ganglion cells. However, hNSC-derived cells around the mouse utricle persisted as immature neurons or occasionally differentiated into putative astrocytes. Moreover, electrophysiological examination showed hNSC-derived cells around utricles did not exhibit any obvious spontaneous firing activities.

Conclusions: Injected human neural stem cells (hNSCs) showed signs of morphological maturation including reconnection to denervated hair cells and partial physiological maturation, suggesting hNSC-derived cells possibly differentiated into neurons.

Keywords:

• Vestibular ganglion cells
• human neural stem cells
• mouse utricle

Acknowledgements

We thank Dr Hotta Akitsu (iPSC Center, Kyoto University) who kindly gifted the human iPSC line 201B7. This research was supported by a Health and Labour Science Research Grant for Research on a Specific Disease (Vestibular Disorders) from the Japanese Ministry of Health, Labour and Welfare, as well as a Grant-in-Aid for Scientific Research from the Japanese Ministry of Education, Science, Sports, Culture and Technology.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.