Elucidation of pathogenic mechanisms of sensorineural hearing loss and establishment of disease model using XP-A patient-derived iPS cells
| Project/Area Number |
15K10748
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Otorhinolaryngology
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| Research Institution | Kyoto University |
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Principal Investigator |
Hireo Ohnishi 京都大学, 医学研究科, 研究員 (50397634)
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| Co-Investigator(Kenkyū-buntansha) |
北尻 真一郎 信州大学, 学術研究院医学系(医学部附属病院), 講師 (00532970)
中川 隆之 京都大学, 医学研究科, 講師 (50335270)
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| Research Collaborator |
YUBA shyunsuke
MATSUDA toshirou
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 疾患特異的iPS細胞 / 神経分化誘導 / 聴神経 / 内耳感覚上皮組織培養 / 色素性乾皮症 / 神経細胞 / シナプス形成 / 共培養 / 分化誘導 |
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| Outline of Final Research Achievements |
To generate auditory nerve degeneration model for XP-A patients, we induced glutamatergic neurons from patient-derived iPSCs using our established induction method. And we generated in vitro model using normal hiPSCs for examination of neuronal functions. We observed the neurite outgrowth into cochlea explants in co-culture. Moreover, to examine the neuronal functions of hiPSC-derived neuron, hiPSC-derived neural stem cells were cultured with vestibular explants and then we performed electrophysiological analysis and histological analysis. As a result, hiPSC-derived neurons expressed the sodium channel and showed the spontaneous firing of nerves. Additionally, to induce the neuron that are more closely similar to auditory nerve, we examined induction method of otic progenitors which generate inner ear nerves and confirmed expression of some markers for otic progenitor in induced cells.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究で確立されたヒトiPS細胞と内耳組織の共培養モデルとXPA患者由来神経幹細胞、神経細胞を用いることにより、XPA KOマウスでは不可能であった、XPA患者の神経変性モデルを作成することが可能になり、XPA患者における難聴発症メカニズムや治療法の検証に役立てることができる。また、ヒトiPS細胞由来内耳前駆細胞を介して内耳神経を誘導して共培養モデルに用いることにより、生体内耳に近いモデルの作出が可能なる。これにより神経変性のメカニズムが明らかになれば、感音性難聴だけでなくXPA患者における神経症状全般への治療の糸口になると予想され、本研究の社会的意義は高いと考えられる。
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Report
(5 results)
Research Products
(7 results)
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[Presentation] Trial for Improvement of Hair Cell Induction Method from Human Induced Pluripotent Stem Cell.2019
Author(s)
Ohnishi H, Skerleva D, Okuyama H, Miyamoto T, Matsuura S, Kirino K, Yamamoto N, Ito J, Omori K, Saito M, Tsukita K, Inoue H and Nakagawa T.
Organizer
Association for Research in Otolaryngology 42th MidWinter Meeting
Related Report
Int'l Joint Research
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