a Differentiation of human pluripotent stem cells into inner ear cells

Abstract

Hearing loss is among the most common of sensory impairments and there are over 500 million deaf individuals in the world. Currently, most treatment strategies depend on acoustic amplification or cochlear implantation in severe cases. These electronic devices can give help to those with hearing loss, but they are not perfect cures for deafness. Over the last decade, stem cell technology has received a great attention as a possible and powerful treatment for a number of diseases. The induction of human inner ear tissue from pluripotent stem cells would be applicable not only to modelling of sensorineural hearing loss disease but also for the generation of clinically useful sensory cells. In this study, we have developed a method for differentiating human pluripotent stem cells to inner ear cells. Using a three-dimensional culture system, we modulated TGF, BMP, and FGF signalling to generate otic vesicle-like structures alongside neural progenitor cells from stem cell embryoid bodies (EBs). Over 3 months, the vesicles developed into EBs that give rise to sensory hair cells bearing stereocilia bundles that are innervated by possible sensory neurons. Additionally, using FM1-43FX we detected hair-cell-like cells and possible sensory neurons that have active mechanotransduction ion channels. We also showed that derived neurons exhibit electrophysiological properties similar to primary auditory neurons of the rat cochlea. Finally, we demonstrated how these otic EBs are structurally and biochemically similar to developing human cochlear and vestibular organs. We believe that this study would facilitate the study of human inner ear development and also could benefit a broad range of individuals suffering from sensorineural hearing loss.