T.S. and M.C.H. contributed equally to this work.
Transplantation of conditionally immortal auditory neuroblasts to the auditory nerve
Version of Record online: 16 APR 2007
European Journal of Neuroscience
Volume 25, Issue 8, pages 2307–2318, April 2007
How to Cite
Sekiya, T., Holley, M. C., Kojima, K., Matsumoto, M., Helyer, R. and Ito, J. (2007), Transplantation of conditionally immortal auditory neuroblasts to the auditory nerve. European Journal of Neuroscience, 25: 2307–2318. doi: 10.1111/j.1460-9568.2007.05478.x
- Issue online: 16 APR 2007
- Version of Record online: 16 APR 2007
- Received 4 September 2006, revised 28 January 2007, accepted 12 February 2007
- cell line;
- cell transplantation;
- hearing loss;
- in vivo;
- spiral ganglion neuron
Cell transplantation is a realistic potential therapy for replacement of auditory sensory neurons and could benefit patients with cochlear implants or acoustic neuropathies. The procedure involves many experimental variables, including the nature and conditioning of donor cells, surgical technique and degree of degeneration in the host tissue. It is essential to control these variables in order to develop cell transplantation techniques effectively. We have characterized a conditionally immortal, mouse cell line suitable for transplantation to the auditory nerve. Structural and physiological markers defined the cells as early auditory neuroblasts that lacked neuronal, voltage-gated sodium or calcium currents and had an undifferentiated morphology. When transplanted into the auditory nerves of rats in vivo, the cells migrated peripherally and centrally and aggregated to form coherent, ectopic ‘ganglia’. After 7 days they expressed β3-tubulin and adopted a similar morphology to native spiral ganglion neurons. They also developed bipolar projections aligned with the host nerves. There was no evidence for uncontrolled proliferation in vivo and cells survived for at least 63 days. If cells were transplanted with the appropriate surgical technique then the auditory brainstem responses were preserved. We have shown that immortal cell lines can potentially be used in the mammalian ear, that it is possible to differentiate significant numbers of cells within the auditory nerve tract and that surgery and cell injection can be achieved with no damage to the cochlea and with minimal degradation of the auditory brainstem response.