Central migration of neuronal tissue and embryonic stem cells following transplantation along the adult auditory nerve

Abstract

The regeneration of the auditory nerve remains a challenge in restoring hearing. An interesting approach would be to use a cell replacement therapy with the potential to establish connections from the inner ear to the central auditory system. This hypothesis was tested by xenografted (mouse to rat) implantation of embryonic dorsal root ganglion (DRG) neurons and embryonic stem (ES) cells along the auditory nerve in the adult host. DRG neurons were obtained at embryonic day 13–14 in transgenic animals expressing enhanced green fluorescence protein (EGFP). For embryonic stem cells, a tau-GFP ES cell line was used as a donor. The fibers of the auditory nerve in the adult rat were transected through the modiolus at the first cochlear turn, and the biological implants were transplanted into the transection. The transplanted DRG neurons and ES cells survived for a postoperative survival time ranging from 3 to 9 weeks, verified by EGFP/GFP fluorescence, and neurofilament or TUJ1 immunostaining. At 9 weeks following implantation, the implanted DRG neurons were found to have migrated along the auditory nerve in the internal meatus. At the same postoperative time, the ES cells had migrated into the brain stem close to the ventral cochlear nucleus. The results demonstrate not only the survival and migration of xenografted DRG neurons and stem cells along the adult auditory nerve but also the feasibility of a cell replacement therapy in the degenerated auditory system.