Migration and differentiation of mouse embryonic stem cells transplanted into mature cochlea of rats with aminoglycoside-induced hearing loss

Abstract

Conclusion: Mouse embryonic stem cells (ESCs) transplanted into the scala tympani are able to migrate in the cochlea of rats deafened with aminoglycoside and partly restore the structure of sensory epithelia of the inner ear. Objectives: To explore the migration and differentiation of enhanced green fluorescence protein (EGFP)-expressing ESCs by transplanting them into the scala tympani of rats with amikacin sulfate-induced hearing loss. Methods: Adult Sprague-Dawley (SD) rats were deafened with amikacin sulfate. Mouse ESCs expressing EGFP (EGFP-ESCs) were transplanted into the scala tympani. The migration and differentiation were observed at different time points. Results: EGFP-ESCs transplanted into normal cochlea did not migrate, but those in the amikacin-damaged cochlea could survive and migrate into the scala media and the vestibular cisterna. For the first time, we observed that the EGFP-ESCs migrated into the scala media, took the place of the organ of Corti, and formed a structure just like the cochlear tunnel. Some grafted stem cells even expressed myosin VIIa, the molecular marker of hair cells. Some nerve fibers reached to the bottom of the hair cell-like cells. The ESCs migrated into the vestibule and restored the sensory epithelia of the ampullary crest. The number of the transplanted ESCs reduced over the 6 week period of the study.

Keywords::

• Hair cell regeneration
• drug-induced hearing loss
• transplantation

Acknowledgments

This work was supported by grants from the National Basic Research Program of China (973 Program) (#2012CB967900, 2011CBA01000), National Hi-Tech Research and Development Program of China (863 Program) (#2007AA02Z150) to S.M.Y., the National Natural Science Foundation of China (NSFC) (#30730040) to S.M.Y., and the National Natural Science Foundation of China (NSFC) (#30871398, 30628030) to S.M.Y.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.