Can neurosphere production help restore inner ear transduction?

T he exquisite sensitivity of the human ear to sound depends on the proper function of mechanosensory hair cells that transduce mechanical stimuli into electrical signals. Sound-induced deflections of bundles of actin-rich microvilli that protrude from the apical surface of hair cells evoke changes in the open probability of nonselective ion channels that modulate cellular excitability and synaptic transmission. The signals are transmitted to auditory spiral ganglion neurons (SGNs) which, in turn, convey the sensory information to the brain. A multitude of factors including excessive noise, trauma, ototoxic drugs, aging, and genetic factors can cause degeneration and death of mechanosensory hair cells and SGNs. Unlike the primary sensory cells for touch, taste, and smell, sensory hair cells do not regenerate in humans; thus, their loss leads to permanent hearing deficits, which collectively are projected to affect 69 million Americans by the year 2030. In a recent issue of PNAS, Wei et al. (1) describe a novel source of precursor cells that could be used to replace lost hair cells and SGNs. Here, we highlight the significance of these findings, the prospects that they may be developed into viable treatment strategies and several challenges that remain. The current state-of-the-art therapy for hearing loss, the cochlear implant, offers only partial restoration of hearing function and is indicated in only a limited number of cases. Deaf patients who have suffered significant hair cell loss but retain auditory SGNs can be considered as candidates for a cochlear implant. The device attempts to reproduce the sensory function of hair cells and stimulates the auditory SGNs electrically. Although a great success story for the field, cochlear implants do not restore the full spectrum of sound frequencies that the human ear can perceive and survival of SGNs is a prerequisite. As such, other therapeutic approaches for restoration of hearing including cellular replacement via stem cell therapy, introduction of exogenous genetic material through gene therapy (2, 3), and pharmacological induction of intrinsic tissue regeneration are being investigated and hold the promise for complete recovery of auditory function. A Novel Source for Hair Cell Replacement In pursuit of a cellular replacement strategy, Wei et al. (1) identified proliferative cells from the ependyma of the lateral ventricles of the adult mouse brain that share similar molecular, morphological, and physiological characteristics with inner ear hair cells and therefore may serve as a potential source for replacement of lost hair cells. In previous work, stem cells have been isolated from various sources and examined for their potential to differentiate into cells with a hair cell-like phenotype. For ex-