Toward Translating Molecular Ear Development to Generate Hair Cells from Stem Cells

Abstract

The ear develops through the transformation of embryonic ectoderm into the labyrinth and, through a stepwise molecular restriction of cell fate options, into cells neurosensory cells (hair cells, neurons) and non-neurosensory cells. Hair cells can degenerate because of age, ototoxic drugs, acoustic trauma or genetic predisposition. Two principle approaches have been developed to restore hair cells that do not regenerate: a cell-based therapy and a gene-based therapy. One approach recapitulates developmental steps to transform embryonic stem cells into hair cells. Alternatively, gene therapy uses the molecular basis of hair cell development to transform remaining cells into hair cells. We review the molecular basis of normal neurosensory development, the state of cell and gene-based approaches, and indicate future improvements to increase the yield from either adult stem cells or embryonic- or adult-induced pluripotent stem cells (ES and iPS).