Stereotaxic delivery of neural progenitors for hearing improvement in mouse

Introduction:

Auditory neurons do not regenerate after damage, and cellular therapies such as transplantation of stem cell derived neural progenitors may offer a promising therapeutic approach, but surgical access to the cochlea is challenging. Minimally invasive stereotaxic surgery has long been used in the brain and may offer a viable approach for the cell based therapies to the cochlear nerve.

Methods:

Tau-GFP expressing mES cells were subjected to a neural induction protocol. The auditory nerve was accessed via a stereotaxic approach in a mouse model of auditory neuropathy. Progenitors were transplanted into the denervated auditory nerve trunk 1 week after damage. Successful engraftment was confirmed by immunohistochemistry and auditory brainstem evoked responses (ABRs).

Results:

Sensory neural progenitors derived from mES cells were successfully transplanted using standardized stereotaxic coordinates. Progenitor cells survived and exhibited neurite outgrowth within the first 10 days of transplantation. After 3 months, neurites were found at the level of the organ of Corti, and functional testing revealed improvement of ABR at several frequencies.

Conclusion:

Stereotaxic transplantation of mES cell derived neural progenitors allows for minimally invasive access to the mouse auditory nerve. Progenitor cells integrate into the adult peripheral and central auditory pathway and improve hearing in mice. This study represents a first step toward future cell based regeneration strategies for hearing loss in the human.