Generation of inner ear cell types from embryonic stem cells.

The senses of hearing and balance are mediated by hair cells located in the cochlea and in the vestibular organs of the vertebrate inner ear. Loss of hair cells and other cell types of the inner ear results in hearing and balance disorders that substantially diminish the quality of life. The irreversibility of hearing loss in mammals is caused by the inability of the cochlea to replace lost hair cells. No drugs are available that stimulate inner ear cell regeneration. We describe here protocols to generate inner ear progenitor cells from murine ES cells and to differentiate these progenitors into hair cells and potentially into other inner ear cell types. In addition, we provide a modification of the protocol describing culture conditions in which human ES cells express a similar set of inner ear markers. Inner ear progenitor cells, generated from ES cells, may be used for the development of cell replacement therapy for the diseased inner ear, for high-throughput drug screening, and for the study of inner ear development.