iPS 細胞を用いた前庭再生医療

抄録

　Vestibular hair cells and vestibular ganglion cells are known to be important for the maintenance of balance systems. However they gradually decrease in number with age. In addition, a large amount of vestibular ganglion cells is lost after vestibular neuritis; meanwhile, the remaining cells degenerate. In addition, hair cells are damaged by ototoxic drugs and complete regeneration is difficult in mammals. In clinical situations, the loss of the bilateral vestibular systems impacts negatively and severely on an affected individual's quality of life. Unfortunately, to date, no fundamental therapy for vestibular disorders has been established. As such, there is an urgent need for new treatment breakthroughs.

　Recently, transplantation of induced pluripotent stem cells (iPSCs) is an extremely promising tool for the treatment of presently incurable diseases. To replace damaged cells in transplanted tissues, transplanted cells must differentiate into target cells. We reported that co-cultures of otic progenitor cells derived from iPSCs with stromal tissues differentiated into vestibular hair cell like cells, and human neural stem cells (hNSCc) derived from iPSCs cultured in utricle tissues differentiated into cells resembling vestibular ganglion cells morphologically and functionally. We examined the potential of transplantation therapy using iPSC-derived cells in mouse utricles with the aim of replacing lost vestibular cells.

　For clinical application, we made a mouse model of vestibular disorders to confirm the effect of cell transplantation in vivo. Administration of an ototoxic drug such as gentamicin into the mouse posterior semicircular canal induced a balance disorder and lowered the vestibulo ocular reflex (VOR) gain. Additionally, a few transplanted iPSCs survived in the mouse inner ear after iPSCs transplantation. These were preliminary data, but might be a first step to future regeneration therapy for vestibular disorders.