Surgical access to the mammalian cochlea for cell-based therapies

Abstract

Cochlear implants are dependent on functionally viable spiral ganglion neurons (SGNs) — the primary auditory neurons of the inner ear. Cell-based therapies are being used experimentally in an attempt to rescue SGNs from deafness-induced degeneration or to generate new neurons. The success of these therapies will be dependent on the development of surgical techniques designed to ensure precise cell placement while minimizing surgical trauma, adverse tissue reaction and cell dispersal. Using 24 normal adult guinea pigs we assessed three surgical procedures for cell delivery into the cochlea: (i) a cochleostomy into the scala tympani (ST); (ii) direct access to Rosenthal's canal – the site of the SGN soma – via a localized fracture of the osseous spiral lamina (RC); and (iii) direct access to the auditory nerve via a translabyrinthine surgical approach (TL). Half the cohort had surgery alone while the other half had surgery combined with the delivery of biocompatible microspheres designed to model implanted cells. Following a four week survival period the inflammatory response and SGN survival were measured for each cohort and the location of microspheres were determined. We observed a wide variability across the three surgical approaches examined, including the extent of the inflammatory tissue response (TL ≫ RC ≥ ST) and the survival of SGNs (ST > RC ≫ TL). Importantly, microspheres were effectively retained at the implant site after all three surgical approaches. Direct access to Rosenthal's canal offered the most promising surgical approach to the SGNs, although the technique must be further refined to reduce the localized trauma associated with the procedure.