01082016 Transplantation of neural stem cells into the modiolus of Mouse cochleae injured by cisplatin

Tetsuya T, Takayuki N, Fukuichiro I, et al. Acta Otolaryngol 2004; Suppl. 551: 65-68.

Summary:

Sound stimulation is adapted by auditory hair cells, converted into electronic stimulation in hair cells and transmitted to Spiral gangolion neurons (SGNs). SGNs are auditory primary neurons in the Rosenthal’s canal in the modiolus of the cochlea.  In humans, degeneration of the auditory nerve in the inner ear is an irreversible which eventually reduces residual hearing in any hearing impaired patient. Cochleae implant (CI) is implantable device designed to stimulate SGNs, it is dependent on the proper transduction of signals and subsequently on the function of the auditory nerve (AN).  The survival of SGNs is therefore a critical issue for maintenance of hearing function, and for obtaining the clinical benefits of CI. For the lesions that primarily affect the AN such as acoustic neuroma, surgery, trauma and auditory neuropahy, CI doesn’t help. Regeneration of SGNs has thus been an important issue for restoration of hearing as their regenerative activity is very limited . New experimental approaches
including cell transplantation are, thus, being pursued to restore hearing .The aim of this study was to examine the potential of cell transplantation for restoration of SGNs.

They use fetal neural stem cells (NSCs) that have the potential for differentiation into neurons as donor cells, and adult mice affected by cisplatin, in which severe degeneration of SGNs is induced as the recipient animals.

Basic methods:

A cisplatin solution (2.5 mg/ml) was injected from the left posterior semicircular canal to deafen the animal. 14 days later the left cochlea of recipient animals was exposed, 2 μl NSC was injected into the cochlea through the round window toward the direction of the cochlear modiolus . 14 days after transplantation, the left cochlea was re-exposed and local perfusion was done, The animals were then sacrificed. The temporal bones were collected . Cryostat sections 10 μm thick were made, and the mid-modiolus sections were used for histological analysis.

The cell fates of grafted NSCs were determined by immunohistochemistry for Tuj 1 (marker for neurons) or GFAP (marker of glial cells). Counterstaining with DAPI. The numbers of transplant-derived cells in the modiolus in one section and the ratios of positivity for each marker in transplant-derived cells were examined. Robust survival of the injected cells was found in cochleae. NSC-derived cells expressing GFP located in the modiolus of cochleae or scala tympani, settled in the apical portion of the modiolus .The mean and standard deviation of numbers of NSC derived cells in the modiolus was 190.5 and 60.8. TuJ1-positive grafted cells were positioned on the periphery of grafted cells, GFAP-positive grafted cells were mainly located in the center of grafted cells.

Why it’s important:

From this paper I get some information about the fate of the fetal NSCs in the modiolus  of the mice and it shows  that TuJ1-positive grafted cells were positioned on the periphery of grafted cells while GFAP-positive grafted cells were mainly located in the center of grafted cells. For my further studies, as I would like to inject the NPCs into the guinea pig’s internal auditory canal bottom, the result of the paper give me inspiration for further study.

lab meeting.ppt

Transplantation of neural stem cells into the modiolus of Mouse cochleae injured by cisplatin

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