Clinical and Experimental Otorhinolaryngology (Jun 2015)

Neural-Induced Human Mesenchymal Stem Cells Promote Cochlear Cell Regeneration in Deaf Guinea Pigs

  • Sujeong Jang,
  • Hyong-Ho Cho,
  • Song-Hee Kim,
  • Kyung-Hwa Lee,
  • Jae Yeoul Jun,
  • Jong-Seong Park,
  • Han-Seong Jeong,
  • Yong-Beom Cho

DOI
https://doi.org/10.3342/ceo.2015.8.2.83
Journal volume & issue
Vol. 8, no. 2
pp. 83 – 91

Abstract

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ObjectivesIn mammals, cochlear hair cell loss is irreversible and may result in a permanent sensorineural hearing loss. Secondary to this hair cell loss, a progressive loss of spiral ganglion neurons (SGNs) is presented. In this study, we have investigated the effects of neural-induced human mesenchymal stem cells (NI-hMSCs) from human bone marrow on sensory neuronal regeneration from neomycin treated deafened guinea pig cochleae.MethodsHMSCs were isolated from the bone marrow which was obtained from the mastoid process during mastoidectomy for ear surgery. Following neural induction with basic fibroblast growth factor and forskolin, we studied the several neural marker and performed electrophysiological analysis. NI-hMSCs were transplanted into the neomycin treated deafened guinea pig cochlea. Engraftment of NI-hMSCs was evaluated immunohistologically at 8 weeks after transplantation.ResultsFollowing neural differentiation, hMSCs expressed high levels of neural markers, ionic channel markers, which are important in neural function, and tetrodotoxin-sensitive voltage-dependent sodium currents. After transplantation into the scala tympani of damaged cochlea, NI-hMSCs-injected animals exhibited a significant increase in the number of SGNs compared to Hanks balanced salt solution-injected animals. Transplanted NI-hMSCs were found within the perilymphatic space, the organ of Corti, along the cochlear nerve fibers, and in the spiral ganglion. Furthermore, the grafted NI-hMSCs migrated into the spiral ganglion where they expressed the neuron-specific marker, NeuN.ConclusionThe results show the potential of NI-hMSCs to give rise to replace the lost cochlear cells in hearing loss mammals.

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