Cell transplantation to the auditory nerve and cochlear duct Tetsuji Sekiya a, ⁎ , Ken Kojima a,b , Masahiro Matsumoto a , Tae-Soo Kim a , Tetsuya Tamura a , Juichi Ito a a Department of Otolaryngology—Head and Neck Surgery, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8507, Japan b Establishment of International Center of Excellence (COE) for Integration of Transplantation Therapy and Regenerative Medicine, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan Received 31 May 2005; revised 22 October 2005; accepted 4 November 2005 Available online 22 December 2005 Abstract We have developed a technique to deliver cells to the inner ear without injuring the membranes that seal the endolymphatic and perilymphatic chambers. The integrity of these membranes is essential for normal hearing, and the technique should significantly reduce surgical trauma during cell transplantation. Embryonic stem cells transplanted at the internal auditory meatal portion of an atrophic auditory nerve migrated extensively along it. Four–five weeks after transplantation, the cells were found not only throughout the auditory nerve, but also in Rosenthal's canal and the scala media, the most distal portion of the auditory nervous system where the hair cells reside. Migration of the transplanted cells was more extensive following damage to the auditory nerve. In the undamaged nerve, migration was more limited, but the cells showed more signs of neuronal differentiation. This highlights an important balance between tissue damage and the potential for repair. © 2005 Elsevier Inc. All rights reserved. Keywords: Auditory nerve; Cell migration; Cell transplantation; Embryonic stem cell; Membranous labyrinth; Spiral ganglion cell Introduction Cell transplantation provides a potential method to replace the irreversible loss of auditory hair cells and neurons that accompanies many forms of permanent hearing loss. A fundamental requisite is to deliver the potentially restorative cells to the target, usually the site of the lesion, with minimal trauma to the homeostasis of the host. This is particularly difficult in the inner ear because it has a highly specialized and complex anatomy (Fig. 1). Hair cells are an important target for cell replacement, but they occupy a critical position at the boundary between the cochlear chambers that enclose the endolymph and perilymph. The differential ionic composition of these fluids is essential for maintenance of the endocochlear potential that provides the driving force for sound transduction. Current surgical techniques in the cochlea break the membranes between the chambers, a process that may disturb or, at worst, abolish the residual hearing of the affected patients. This issue applies not only to cell transplantation (Bianchi and Raz, 2004; Brown et al., 1993; Holley, 2002; Ito et al., 2001; Izumikawa et al., 2005; Staecker et al., 2001)(Figs. 1, [1, 1′]– [3]) but also to the inoculation of vectors used for gene transfection (Bianchi and Raz, 2004; Izumikawa et al., 2005) (Fig. 1, [1]). One alternative is to deliver materials into the endolymphatic space through the vestibular aqueduct (Fig. 1, [1′]). However, these procedures may potentially put endolym- phatic structures at risk of injury. Another problem with this technique is that the injected materials may enter not only the cochlear but also the vestibular portion of the membranous labyrinth (Fig. 1). An osmotic pump can be used to deliver various materials such as cells, viral vectors, or pharmacological agents into the perilymphatic space (Brown et al., 1993)(Fig. 1, [2]). Although direct damage to the endolymphatic structures may be attenuated with this technique, this approach may not be totally free from hearing loss due to perilymphatic fluid fistula (Minor, 2003). Another potential danger of one perilymphatic injection technique is that the injected materials could enter the cochlear aqueduct (Fig. 1, CA) and travel through cerebrospinal fluid to the contralateral ear where they could cause unintended effects. More indirectly, the round window niche has been used as the Experimental Neurology 198 (2006) 12 – 24 www.elsevier.com/locate/yexnr ⁎ Corresponding author. Fax: +81 75 751 7225. E-mail address: tsekiya@ent.kuhp.kyoto-u.ac.jp (T. Sekiya). 0014-4886/$ - see front matter © 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.expneurol.2005.11.006