Sensorineural hearing loss is very difficult to treat. Currently, one of the techniques used for hearing rehabilitation is a cochlear implant that can transform sound into electrical signals instead of inner ear hair cells. However, the prognosis remains very poor if sufficient auditory nerve cells are not secured. In this study, the effect of mouse embryonic stem cells (mESC) and photobiomodulation (PBM) combined treatment on auditory function and auditory nerve cells in a secondary neuropathy animal model was investigated. To confirm the engraftment of stem cells in vitro, cochlear explants were treated with kanamycin (KM) to mimic nerve damage and then cocultured with GFP-mESC. GFP-mESCs were observed to have attached and integrated into the explanted samples. An animal model for secondary neurodegeneration was achieved by KM treatment and was treated by a combination therapy of GFP-mESC and NIR-PBM at 8 weeks of KM treatment. Hearing recovery by functional testing using auditory brain stem response (ABR) and eABR was measured as well as morphological changes and epifluorescence analysis were conducted after 2 weeks of combination therapy. KM treatment elevated the hearing threshold at 70-80 dB and even after the combination treatment with GFP-mESC and PBM was applied, the auditory function was not restored. In addition, the stem cells transplanted into cochlea has exponentially increased due to PBM treatment although did not produce any malignancy. This study confirmed that the combined treatment with mESC and PBM could not improve hearing or increase the response of the auditory nerve. Nevertheless, it is noteworthy in this study that the cells are distributed in most cochlear tissues and the proliferation of stem cells was very active in animals irradiated with PBM compared to other groups wherein the stem cells had disappeared immediately after transplantation or existed for only a short period of time.
机构:
Univ Washington, Dept Pathol, Ctr Cardiovasc Biol, Seattle, WA 98195 USA
Univ Washington, Inst Stem Cell & Regenerat Med, Seattle, WA 98195 USA
Sunnybrook Res Inst, Dept Phys Sci, Toronto, ON, CanadaUniv Washington, Dept Pathol, Ctr Cardiovasc Biol, Seattle, WA 98195 USA
Weyers, Jill J.
Gunaje, Jagadambika J.
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Univ Washington, Dept Pathol, Ctr Cardiovasc Biol, Seattle, WA 98195 USA
Univ Washington, Inst Stem Cell & Regenerat Med, Seattle, WA 98195 USAUniv Washington, Dept Pathol, Ctr Cardiovasc Biol, Seattle, WA 98195 USA
Gunaje, Jagadambika J.
Van Biber, Benjamin
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Univ Washington, Dept Pathol, Ctr Cardiovasc Biol, Seattle, WA 98195 USA
Univ Washington, Inst Stem Cell & Regenerat Med, Seattle, WA 98195 USAUniv Washington, Dept Pathol, Ctr Cardiovasc Biol, Seattle, WA 98195 USA
Van Biber, Benjamin
Martinson, Amy
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Univ Washington, Dept Pathol, Ctr Cardiovasc Biol, Seattle, WA 98195 USA
Univ Washington, Inst Stem Cell & Regenerat Med, Seattle, WA 98195 USAUniv Washington, Dept Pathol, Ctr Cardiovasc Biol, Seattle, WA 98195 USA
Martinson, Amy
Reinecke, Hans
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Univ Washington, Dept Pathol, Ctr Cardiovasc Biol, Seattle, WA 98195 USA
Univ Washington, Inst Stem Cell & Regenerat Med, Seattle, WA 98195 USAUniv Washington, Dept Pathol, Ctr Cardiovasc Biol, Seattle, WA 98195 USA
Reinecke, Hans
Mahoney, William M.
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Univ Washington, Dept Pathol, Ctr Cardiovasc Biol, Seattle, WA 98195 USA
Univ Washington, Inst Stem Cell & Regenerat Med, Seattle, WA 98195 USAUniv Washington, Dept Pathol, Ctr Cardiovasc Biol, Seattle, WA 98195 USA
Mahoney, William M.
Schwartz, Stephen M.
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Univ Washington, Dept Pathol, Ctr Cardiovasc Biol, Seattle, WA 98195 USA
Univ Washington, Inst Stem Cell & Regenerat Med, Seattle, WA 98195 USAUniv Washington, Dept Pathol, Ctr Cardiovasc Biol, Seattle, WA 98195 USA
Schwartz, Stephen M.
Cox, Timothy C.
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机构:
Seattle Childrens Res Inst, Ctr Dev Biol & Regenerat Med, Seattle, WA USA
Univ Washington, Dept Pediat, Seattle, WA 98195 USA
Univ Missouri, Dept Oral & Craniofacial Sci, Kansas City, MO 64110 USAUniv Washington, Dept Pathol, Ctr Cardiovasc Biol, Seattle, WA 98195 USA
Cox, Timothy C.
Murry, Charles E.
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Univ Washington, Dept Pathol, Ctr Cardiovasc Biol, Seattle, WA 98195 USA
Univ Washington, Inst Stem Cell & Regenerat Med, Seattle, WA 98195 USA
Univ Washington, Dept Med Cardiol, Seattle, WA 98195 USA
Univ Washington, Dept Bioengn, Seattle, WA 98195 USAUniv Washington, Dept Pathol, Ctr Cardiovasc Biol, Seattle, WA 98195 USA
机构:
Yeungnam Univ, Coll Pharm, Gyongsan 38541, South KoreaYeungnam Univ, Coll Pharm, Gyongsan 38541, South Korea
Shrestha, Prakash
Pathak, Shiva
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Yeungnam Univ, Coll Pharm, Gyongsan 38541, South Korea
Stanford Univ, Div Blood & Marrow Transplantat, Sch Med, Stanford, CA 94305 USAYeungnam Univ, Coll Pharm, Gyongsan 38541, South Korea
Pathak, Shiva
Regmi, Shobha
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Yeungnam Univ, Coll Pharm, Gyongsan 38541, South Korea
Stanford Univ, Dept Radiol, Sch Med, Palo Alto, CA 94304 USAYeungnam Univ, Coll Pharm, Gyongsan 38541, South Korea
Regmi, Shobha
Narayanan, Kannan Badri
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Yeungnam Univ, Sch Chem Engn, Gyongsan 38541, South KoreaYeungnam Univ, Coll Pharm, Gyongsan 38541, South Korea
Narayanan, Kannan Badri
Nguyen, Tiep Tien
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机构:
Keimyung Univ, Coll Pharm, Daegu 42601, South KoreaYeungnam Univ, Coll Pharm, Gyongsan 38541, South Korea
Nguyen, Tiep Tien
Yook, Simmyung
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Sungkyunkwan Univ, Sch Med, Dept Precis Med, Suwon, South KoreaYeungnam Univ, Coll Pharm, Gyongsan 38541, South Korea
Yook, Simmyung
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Kim, Jong Oh
Jeong, Jee-Heon
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Sungkyunkwan Univ, Sch Med, Dept Precis Med, Suwon, South Korea
Sungkyunkwan Univ, Sch Med, Dept Precis Med, Suwon 16419, South KoreaYeungnam Univ, Coll Pharm, Gyongsan 38541, South Korea
机构:
Great Ormond St Hosp Sick Children, Paediat Oncol, London WC1N 3JH, EnglandGreat Ormond St Hosp Sick Children, Paediat Oncol, London WC1N 3JH, England
Morgenstern, D.
Brocklesby, M.
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机构:
Great Ormond St Hosp Sick Children, Cell Therapy Lab, London WC1N 3JH, EnglandGreat Ormond St Hosp Sick Children, Paediat Oncol, London WC1N 3JH, England
Brocklesby, M.
Ahsan, G.
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Great Ormond St Hosp Sick Children, Cell Therapy Lab, London WC1N 3JH, EnglandGreat Ormond St Hosp Sick Children, Paediat Oncol, London WC1N 3JH, England
Ahsan, G.
Watts, M.
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机构:
Univ Coll London Hosp, Wolfson Cellular Therapy Unit, London, EnglandGreat Ormond St Hosp Sick Children, Paediat Oncol, London WC1N 3JH, England
Watts, M.
Cale, C.
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Great Ormond St Hosp Sick Children, Cell Therapy Lab, London WC1N 3JH, EnglandGreat Ormond St Hosp Sick Children, Paediat Oncol, London WC1N 3JH, England
机构:
College of Pharmacy, Yeungnam University, Gyeongsan,38541, Korea, Republic ofCollege of Pharmacy, Yeungnam University, Gyeongsan,38541, Korea, Republic of
Shrestha, Prakash
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Pathak, Shiva
Regmi, Shobha
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机构:
College of Pharmacy, Yeungnam University, Gyeongsan,38541, Korea, Republic of
Department of Radiology, Stanford University School of Medicine, Palo Alto,CA,94304, United StatesCollege of Pharmacy, Yeungnam University, Gyeongsan,38541, Korea, Republic of
Regmi, Shobha
Narayanan, Kannan Badri
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机构:
School of Chemical Engineering, Yeungnam University, Gyeongsan,38541, Korea, Republic ofCollege of Pharmacy, Yeungnam University, Gyeongsan,38541, Korea, Republic of
Narayanan, Kannan Badri
Nguyen, Tiep Tien
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机构:
College of Pharmacy, Keimyung University, Daegu,42601, Korea, Republic ofCollege of Pharmacy, Yeungnam University, Gyeongsan,38541, Korea, Republic of
Nguyen, Tiep Tien
Yook, Simmyung
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机构:
Department of Precision Medicine, School of Medicine, Sungkyunkwan University, Suwon, Korea, Republic ofCollege of Pharmacy, Yeungnam University, Gyeongsan,38541, Korea, Republic of
机构:
Univ British Columbia, Michael Smith Labs, Vancouver, BC V6T 1Z4, Canada
Univ British Columbia, Dept Med Genet, Vancouver, BC V6T 1Z3, CanadaUniv British Columbia, Michael Smith Labs, Vancouver, BC V6T 1Z4, Canada
Willis, Ashleigh
Jeong, Danielle
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机构:
Hosp Sick Children, Program Neurosci & Mental Hlth, Toronto, ON M5G 0A4, Canada
Univ Toronto, Inst Med Sci, Toronto, ON M5S 1A8, CanadaUniv British Columbia, Michael Smith Labs, Vancouver, BC V6T 1Z4, Canada
Jeong, Danielle
Liu, Yunlong
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Hosp Sick Children, Program Neurosci & Mental Hlth, Toronto, ON M5G 0A4, CanadaUniv British Columbia, Michael Smith Labs, Vancouver, BC V6T 1Z4, Canada
Liu, Yunlong
Lithopoulos, Marissa A.
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机构:
Univ British Columbia, Michael Smith Labs, Vancouver, BC V6T 1Z4, Canada
Hosp Sick Children, Program Neurosci & Mental Hlth, Toronto, ON M5G 0A4, CanadaUniv British Columbia, Michael Smith Labs, Vancouver, BC V6T 1Z4, Canada
Lithopoulos, Marissa A.
Yuzwa, Scott A.
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Hosp Sick Children, Program Neurosci & Mental Hlth, Toronto, ON M5G 0A4, Canada
Univ Toronto, Dept Lab Med & Pathobiol, 1 Kings Coll Circle, Toronto, ON M5S 1A8, CanadaUniv British Columbia, Michael Smith Labs, Vancouver, BC V6T 1Z4, Canada
Yuzwa, Scott A.
Frankland, Paul W.
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Hosp Sick Children, Program Neurosci & Mental Hlth, Toronto, ON M5G 0A4, Canada
Univ Toronto, Inst Med Sci, Toronto, ON M5S 1A8, Canada
Univ Toronto, Dept Physiol, Toronto, ON M5S 1A8, Canada
Univ Toronto, Dept Psychol, Toronto, ON M5S 1A8, CanadaUniv British Columbia, Michael Smith Labs, Vancouver, BC V6T 1Z4, Canada
Frankland, Paul W.
Kaplan, David R.
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机构:
Univ British Columbia, Michael Smith Labs, Vancouver, BC V6T 1Z4, Canada
Univ British Columbia, Dept Med Genet, Vancouver, BC V6T 1Z3, Canada
Hosp Sick Children, Program Neurosci & Mental Hlth, Toronto, ON M5G 0A4, Canada
Univ Toronto, Inst Med Sci, Toronto, ON M5S 1A8, Canada
Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, CanadaUniv British Columbia, Michael Smith Labs, Vancouver, BC V6T 1Z4, Canada
Kaplan, David R.
Miller, Freda D.
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机构:
Univ British Columbia, Michael Smith Labs, Vancouver, BC V6T 1Z4, Canada
Univ British Columbia, Dept Med Genet, Vancouver, BC V6T 1Z3, Canada
Hosp Sick Children, Program Neurosci & Mental Hlth, Toronto, ON M5G 0A4, Canada
Univ Toronto, Inst Med Sci, Toronto, ON M5S 1A8, Canada
Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, CanadaUniv British Columbia, Michael Smith Labs, Vancouver, BC V6T 1Z4, Canada