Transplantation of human limbus–derived mesenchymal stromal cells via occipital approach improves hearing in animal auditory neuropathy

Publication date: Available online 15 November 2018

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Hsin-Chien Chen, Chang-Min Liang, Chih-Hung Wang, Ming-Yuan Huang, Yuan-Yung Lin, Cheng-Ping Shih, Chao-Yin Kuo, Yi-Chun Lin, Hang-Kang Chen

Abstract

Objective

To develop a surgical approach for cell transplantation into mouse cochlear nerves via an intracranial route and investigate whether transplantation of human limbus–derived mesenchymal stromal cells (HL-MSCs) can improve hearing in this model of auditory neuropathy.

Methods

We used 8-week-old CBA/CaJ male mice and created ouabain-induced auditory neuropathy. The surgical approach passed through the cerebellum to reveal the superior semicircular canal and brainstem, allowing access to the auditory nerve. Then HL-MSCs were injected around the cochlear nerve trunk using a micropipette driven by a micropump. Hearing thresholds in the mice were determined by auditory brainstem responses (ABRs) and distortion product otoacoustic emissions (DPOAEs).

Results

We produced ouabain-induced neuropathy in mice with an elevated hearing threshold but normal DPOAE. Using immunohistological staining, we detected HL-MSCs were localized in the cochlear nerve trunk 2 days after cell transplantation via this occipital approach. More spiral ganglion neurons were detected in ouabain-treated cochleae 3 months after HL-MSCs transplantation compared to those without HL-MSCs transplantation. The ABR showed significant hearing improvement 3 months after HL-MSCs transplantation.

Conclusions

We successfully established a mouse model for cell transplantation into the intracranial cochlear nerve trunk and showed that HL-MSCs potentially can be applied as cell therapy to treat sensorineural hearing loss.

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