The adult mammalian cochlea lacks regenerative capacity, which is the main reason for the permanence of hearing loss. Vestibular organs, in contrast, replace a small number of lost hair cells. The reason for this difference is unknown. In this work we show isolation of sphere-forming stem cells from the early postnatal organ of Corti, vestibular sensory epithelia, the spiral ganglion, and the stria vascularis. Organ of Corti and vestibular sensory epithelial stem cells give rise to cells that express multiple hair cell markers and express functional ion channels reminiscent of nascent hair cells. Spiral ganglion stem cells display features of neural stem cells and can give rise to neurons and glial cell types. We found that the ability for sphere formation in the mouse cochlea decreases about 100-fold during the second and third postnatal weeks; this decrease is substantially faster than the reduction of stem cells in vestibular organs, which maintain their stem cell population also at older ages. Coincidentally, the relative expression of developmental and progenitor cell markers in the cochlea decreases during the first 3 postnatal weeks, which is in sharp contrast to the vestibular system, where expression of progenitor cell markers remains constant or even increases during this period. Our findings indicate that the lack of regenerative capacity in the adult mammalian cochlea is either a result of an early postnatal loss of stem cells or diminishment of stem cell features of maturing cochlear cells.
Sound localization and speech intelligibility were assessed in 5 patients implanted bilaterally with Medel C40+ or Medel C40 cochlear implant (CI) systems. The minimum audible angle (MAA) around the head in the horizontal plane was assessed in patients with bilateral CI using white noise bursts of 1000 ms duration presented from a loudspeaker mounted on a rotating boom and compared with the MAA of age-matched normal hearing controls. Spatial discrimination was found to be good in front and in the back of the head with near-normal MAA values (patients: 3–8°, controls: 1–4°). In contrast, poor performance on the sides was found (patients: 30 to over 45°, controls 7–10°). Bilateral CI significantly improved spatial discrimination in front for all patients, when compared with the use of either CI alone. Just noticeable differences (JNDs) in interaural intensity and time were assessed using white noise bursts (1000 ms duration; 50 ms linear ramp). In addition, interaural time JNDs were assessed using click trains (800 ms duration, 40 µs clicks, 50 Hz) and noise bursts in which either only the envelope or only the fine structure was shifted in time. In comparison with normal hearing controls, patients with bilateral CI showed near-normal interaural intensity JNDs but substantially poorer interaural time JNDs depending on the type of stimulus. In contrast to envelope onset/offset cues, interaural fine structure time differences were not perceived by the patients using CI systems employing the continuous interleaved sampling strategy without synchronization between their pulse stimulation times. Speech intelligibility in quiet and CCITT noise from the side (±90°) was assessed using the German HSM sentence test and was significantly better when using bilateral CI in comparison with either unilateral CI, mainly due to a head shadow effect. These favorable results are in agreement with the patients’ subjective experiences assessed with a questionnaire and support the use of bilateral CI.
Sensory hair cells located in the organ of Corti are essential for cochlear mechanosensation. Their loss is irreversible in humans resulting in permanent hearing loss. The development of therapeutic interventions for hearing loss requires fundamental knowledge about similarities and potential differences between animal models and human development as well as the establishment of human cell based-assays. Here we analyze gene and protein expression of the developing human inner ear in a temporal window spanning from week 8 to 12 post conception, when cochlear hair cells become specified. Utilizing surface markers for the cochlear prosensory domain, namely EPCAM and CD271, we purify postmitotic hair cell progenitors that, when placed in culture in three-dimensional organoids, regain proliferative potential and eventually differentiate to hair cell-like cells in vitro. These results provide a foundation for comparative studies with otic cells generated from human pluripotent stem cells and for establishing novel platforms for drug validation.
In this prospective multicenter study, tinnitus loudness and tinnitus-related distress were investigated in 174 cochlear implant (CI) candidates who underwent CI surgery at a Swiss cochlear implant center. All subjects participated in two session, one preoperatively and one 6 months after device activation. In both sessions, tinnitus loudness was assessed using a visual analogue scale and tinnitus distress using a standardized tinnitus questionnaire. The data were compared with unaided pre- and postoperative pure tone thresholds, and postoperative speech reception scores. 71.8% of the subjects reported tinnitus preoperatively. Six months after CI surgery 20.0% of these reported abolition of their tinnitus, 51.2% a subjective improvement, 21.6% no change and 7.2% a deterioration. Of the 49 (28.2%) subjects with no tinnitus preoperatively, 5 developed tinnitus 6 months after CI. These 5 had poorer speech understanding after CI surgery with their device than the group who remained tinnitus free. We found no correlation between tinnitus improvement, age, duration of tinnitus, or change in unaided hearing thresholds between the two sessions.
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