title: 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: OBJECTIVE
  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.
authors.affiliation: a Department of Otolaryngology, Head and Neck Surgery , Kyoto University Hospital/Graduate School of Medicine, Kyoto University , Kyoto , Japan ;
authors.forename: Akiko
authors.initials: A
authors.lastname: Taura
authors.affiliation: b Department of Physiology , Kurume University Hospital/Graduate School of Medicine, Kurume University , Kurume , Japan ;
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Nakashima
authors.affiliation: a Department of Otolaryngology, Head and Neck Surgery , Kyoto University Hospital/Graduate School of Medicine, Kyoto University , Kyoto , Japan ;
authors.forename: Hiroe
authors.initials: H
authors.lastname: Ohnishi
authors.affiliation: a Department of Otolaryngology, Head and Neck Surgery , Kyoto University Hospital/Graduate School of Medicine, Kyoto University , Kyoto , Japan ;
authors.forename: Takayuki
authors.initials: T
authors.lastname: Nakagawa
authors.affiliation: c Institute of Biomedical Research and Innovation , Kobe , Japan ;
authors.forename: Kazuo
authors.initials: K
authors.lastname: Funabiki
authors.affiliation: a Department of Otolaryngology, Head and Neck Surgery , Kyoto University Hospital/Graduate School of Medicine, Kyoto University , Kyoto , Japan ;|d Shiga Medical Center Research Institute , Shiga , Japan.
authors.forename: Juichi
authors.initials: J
authors.lastname: Ito
authors.affiliation: a Department of Otolaryngology, Head and Neck Surgery , Kyoto University Hospital/Graduate School of Medicine, Kyoto University , Kyoto , Japan ;
authors.forename: Koichi
authors.initials: K
authors.lastname: Omori
mesh_terms: D000818:Animals; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000637:transplantation*; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D055495:Neurogenesis; D018408:Patch-Clamp Techniques; D012444:Saccule and Utricle / Q000166:cytology*; D015837:Vestibular Diseases / Q000628:therapy*; D061566:Voltage-Gated Sodium Channels / Q000378:metabolism
chemical_list: D061566:Voltage-Gated Sodium Channels
keywords: Vestibular ganglion cells; human neural stem cells; mouse utricle