Journal
INTERNATIONAL JOURNAL OF PEDIATRIC OTORHINOLARYNGOLOGY
Volume 117, Issue -, Pages 67-72Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.ijporl.2018.11.018
Keywords
Limbus; Mesenchymal stromal cell; Stem cell; Cochlea; Auditory neuropathy; Sensorineural hearing loss
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Funding
- Ministry of Science and Technology, Taiwan, ROC [MOST 103-2314-B-016-018-MY2, MOST 105-2314-B-016-042]
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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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