Regenerative Cell Therapy for the Sensorineural Hearing Loss

Kyoung Ho Park

doi:10.7599/hmr.2015.35.2.113

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Park: Regenerative Cell Therapy for the Sensorineural Hearing Loss

Review Article

Hanyang Medical Reviews 2015; 35(2): 113-120.

Published online: 21 May 2015

DOI: https://doi.org/10.7599/hmr.2015.35.2.113

Regenerative Cell Therapy for the Sensorineural Hearing Loss

Kyoung Ho Park

Department of Otorhinolaryngology-Head and Neck Surgery, The Catholic University of Korea, College of Medicine, Seoul, Korea.

Correspondence to: Kyoung Ho Park. Department of Otorhinolaryngology-Head and Neck Surgery, Seoul St. Mary's Hospital, 222 Banpo-daero, Seocho-gu, Seoul 137-701, Korea. Tel: +82-2-2258-6213, Fax: +82-2-595-1354, khpent@catholic.ac.kr

Received 22 February 2015 Revised 18 March 2015 Accepted 23 March 2015

(open-access):

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Sensorineural hearing loss is the most common disability in the world and nearly one third of all individuals over the age of 65 are affected. For hearing handicapped people, many devices (hearing aid, cochlear implant, middle ear implant etc.) have been developed to reduce or overcome the disability. But these devices do not give perfect benefit to the patients functionally and there are aesthetic problems. That is why researchers have interest in regenerative measures to restore or prevent hearing loss. Recently there were fruitful results from gene and stem cell therapy research for hearing loss. Gene therapy with Atoh 1 gene and transplantation of stem cells into the cochlea regenerate damaged hair cells and morphologically restore spiral ganglion neurons allowing functional hearing in the deaf animal model. Based on these results, many countries including Korea have done clinical trials in deaf patients. The past ten years have shown an incredible advancement in medical biotechnology in the otologic field and this progress may someday substitute the medical devices for the hard of hearing patients.

Keywords: Hearing Loss, Sensorineural, Regenerative Medicine, Stem Cells

Figures and Tables

Fig. 1

Prevalence of bilateral hearing loss (>40 dBHL) among the Korean poplation (>12 years old) (data from the Korean National Health and Nutrition Examination Survey 2009-2012).

Fig. 2

RT-PCR analyses of gene expression of the differentiated cells from the cultured bone marrow derived mesenchymal stem cell.

GAPDH, glyceraldehyde-3-phosphate dehydrogenase; GFAP, glial fibrillary acidic proten; BMP4, bone morphology protein 4.

Fig. 3

(A-P) Double-labeled immunocytochemistry of hair cells differentiated from the umbilical cord blood derived mesenchymal stem cell. Nuclei counterstained with DAPI (blue); stained with BrdU (green); all markers visualized with Alexa 555 (red). (D, H, L, P) Merged images, (400, n=3, bars; 50 µm). (Q) RT-PCR analyses of gene expression of hair cells and specific markers.

BrdU, 5-bromo-2'-deoxy-uridine; DAPI, 4,6-diamidino-2-phenylindole; Sp, neurosphere medium; Ne, neuronal medium.

Fig. 4

(A) Auditory brain response (ABR) results compared between normal hearing, SNHL, and UCB-MSC transplantation groups (Top). Click-evoked ABR waves were recorded up to 10 dB in guinea pigs with normal hearing. Three days after application of ouabain and neomycin to the middle ear, an increase was noted in the ABR threshold. After intravenous injection, the UCB-MSC group showed a significant improvement in hearing threshold compared to that for the SNHL group. (B) Representative graph showing the hearing and non-hearing area of each group. Regeneration of SGNs after UCB-MSCs transplantation (Bottom). (C) Severe loss of SGNs from the basal to the apical turn of the cochlea was observed in the SNHL group. (D) Five weeks after transplantation of UCB-MSCs, SGNs were regenerated in all the turns of the cochlea (H & E staining [inside: 40_; n=5; bars, 1.0 mm. outside: 200_; n=5; bars,100 µm]).

SNHL, sensorineural nearingloss; UCB-MSC, umbilical cord derived mesenchymal stem cell; SGN, spiral ganglion neuron.

Fig. 5

Endogenous stem cell in the ear. Each part of the ear has its somatic stem cells and it can be used in cell therapy in the future.

Table 1

The number of spiral ganglion cells in a Rosenthal's canal in each group

Group 1 (BDNF+GDNF+NT-3) on 5 week after the treatment, Group 2 (IGF-1) and Group 3 (EGF+FGF) on 3 week after the treatment.

^*P<0.05, significant difference compared with control group.

BDNF, brain derived neurotrophic factor; GDNF, glial cell derived neurotrophic factor; IGF-1, insulin growth factor-1; NT-3, neurotrophin 3; EGF, epidermal growth factor; FGF, fibroblast growth factor.

ACKNOWLEDGMENT

This research was supported by the Basic Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education, Science and Technology (2010-0022231)

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ORCID iDs: Kyoung Ho Park
https://orcid.org/http://orcid.org/0000-0003-1485-3250
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