Possible application of regenerative medicine to bilateral vestibulopathy

Abstract

　In our aging society, maintaining one's equilibrium is very important. However, the risk of falling gradually increases with age, because of various hypofunctions, including vestibular disorders. Until date, no curative therapy for vestibular disorders has been established. So, the development of new treatments for vestibular disorders is one of the most urgent needs for our aging society. Vestibular hair cells and vestibular ganglion cells are the main sites of peripheral vestibular damage. Both are related to age-related equilibrium disorders, as the number of these cells decrease with aging. Recently, cell transplantation therapy has become a major focus of clinical research in various fields, such as ophthalmology, neuronal research and so on. Cell transplantation therapy might be a promising tool for severe damage of the peripheral vestibular system. We demonstrated that induced pluripotent stem cells (iPSCs) and human neural stem cells (hNSCs) can morphologically differentiate into hair cell- and vestibular ganglion cell-like cells, respectively, in vitro. These cells have potential as donor cells for transplantation therapy of vestibular disorders. We established animal models of bilateral vestibular disorders using 2 kinds of ototoxic drugs to produce target-specific damage. We used an aminoglycoside to produce hair cell damage and an inhibitor of sodium-potassium ATPase to produce vestibular ganglion cell damage. For evaluation of the vestibular functions, we also examined the vestibulo-ocular reflex (VOR) and performed vestibular function tests such as circling behavior, trunk curling, and swimming ability. Both VOR gain and vestibular disorders decreased after bilateral application of ototoxic drugs. At present, we are investigating the effectiveness of cell transplantation using animal model in vivo. Morphologically, we could observe survival of the transplanted cells, but no differentiation into the desired cells. However, partial improvement of the vestibular function was observed in the transplanted animals. Although extensive investigations are required, cell transplantation might offer promise as a new regenerative therapy for bilateral vestibular disorders.