title: Neural-induced human mesenchymal stem cells promote cochlear cell regeneration in deaf Guinea pigs.
abstract: OBJECTIVE
  In 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.
  
  
  METHODS
  HMSCs 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.
  
  
  RESULTS
  Following 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.
  
  
  CONCLUSIONS
  The results show the potential of NI-hMSCs to give rise to replace the lost cochlear cells in hearing loss mammals.
authors.affiliation: Department of Physiology, Chonnam National University Medical School, Gwangju, Korea. ; The Brain Korea 21 Project, Center for Biomedical Human Resources at Chonnam National University, Gwangju, Korea. ; Research Institute of Medical Sciences, Chonnam National University, Gwangju, Korea.
authors.forename: Sujeong
authors.initials: S
authors.lastname: Jang
authors.affiliation: Research Institute of Medical Sciences, Chonnam National University, Gwangju, Korea. ; Department of Otolaryngology-Head and Neck Surgery, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Hyong-Ho
authors.initials: HH
authors.lastname: Cho
authors.affiliation: Department of Physiology, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Song-Hee
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Research Institute of Medical Sciences, Chonnam National University, Gwangju, Korea. ; Department of Pathology, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Kyung-Hwa
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Department of Physiology, Chosun University College of Medicine, Gwangju, Korea.
authors.forename: Jae Yeoul
authors.initials: JY
authors.lastname: Jun
authors.affiliation: Department of Physiology, Chonnam National University Medical School, Gwangju, Korea. ; The Brain Korea 21 Project, Center for Biomedical Human Resources at Chonnam National University, Gwangju, Korea. ; Research Institute of Medical Sciences, Chonnam National University, Gwangju, Korea.
authors.forename: Jong-Seong
authors.initials: JS
authors.lastname: Park
authors.affiliation: Department of Physiology, Chonnam National University Medical School, Gwangju, Korea. ; The Brain Korea 21 Project, Center for Biomedical Human Resources at Chonnam National University, Gwangju, Korea. ; Research Institute of Medical Sciences, Chonnam National University, Gwangju, Korea.
authors.forename: Han-Seong
authors.initials: HS
authors.lastname: Jeong
authors.affiliation: Research Institute of Medical Sciences, Chonnam National University, Gwangju, Korea. ; Department of Otolaryngology-Head and Neck Surgery, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Yong-Beom
authors.initials: YB
authors.lastname: Cho
keywords: Cell Differentiation; Hair Cells, Auditory; Hearing Loss; Mesenchymal Stem Cells; Transplantation