前庭再生医療研究の将来展望

In our aging society, it is important to maintain a healthy balance. However, the risk of falling gradually increases with age because of various hypofunctions such as vestibular disorders. In birds, hair cells regenerate after damage caused by ototoxic drugs; however, their regeneration in mammals is poor. To date, no curative therapy for vestibular disorders has been established. Therefore, the development of new treatments is an important theme in our aging society. In the mammalian vestibule, spontaneous regeneration has been reported morphologically. However, it is not clear whether regenerated hair cells possess their correct function. We investigated the mechano-electrical transduction (MET) function of hair cells by measuring Ca^２＋ responses. We found an intact MET function in stimulated regenerated hair bundles. However, the self-repair of hair cells was only partial and insufficient to recover vestibular function. Therefore, additional treatments such as with anti-oxidant drugs, growth factors are needed. We also demonstrated that espin gene therapy restored stereocilia on regenerated hair cells after damage. Therefore, cell transplantation therapy might be promising for severe damage of the inner ear. We previously reported that induced pluripotent stem cells and human neural stem cells (hNSCs) differentiated into hair cells and vestibular ganglion cell-like cells, respectively. Therefore, these cells might be potential donor cells for the transplantation therapy of vestibular disorders. Currently, we are investigating the effectiveness of cell transplantation in vivo using an animal model. Morphologically, we confirmed the survival of transplanted cells in normal mice but without their differentiation into the desired cells. To evaluate vestibular function, we also examined the vestibulo-ocular reflex (VOR) and observed a decrease in VOR gain after the application of ototoxic drugs. We confirmed the functional effectiveness of cell transplantation in an animal model of vestibular disorders. Future studies should determine the optimal conditions for donors and recipients. Before new regenerative therapy can be established, further investigations are required.