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KAKEN_26670748seika.pdf
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| Title |
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ヒトES/iPS細胞由来の内耳細胞を用いた薬剤スクリーニング系の構築
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ヒト ES/iPS サイボウ ユライ ノ ナイジ サイボウ オ モチイタ ヤクザイ スクリーニングケイ ノ コウチク
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Hito ES/iPS saibo yurai no naiji saibo o mochiita yakuzai sukuriningukei no kochiku
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Drug screening and development using hES/iPSC-derived otic progenitor
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小川, 郁
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オガワ, カオル
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Ogawa, Kaoru
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慶應義塾大学・医学部・教授
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Research team head
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科研費研究者番号 : 00169179
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藤岡, 正人
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フジオカ, マサト
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Fujioka, Masato
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慶應義塾大学・医学部・専任講師
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Research team member
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科研費研究者番号 : 70398626
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水足, 邦雄
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ミズタリ, クニオ
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Mizutari, Kunio
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独立行政法人国立病院機構(東京医療センター臨床研究センター)・医師
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Research team member
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科研費研究者番号 : 40338140
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2017
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科学研究費補助金研究成果報告書
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2016
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内耳は側頭骨の奥深くに位置しその採取は高度難聴を引き起こすため, ヒト内耳細胞を用いた研究は技術的困難からこれまで行われてこなかった。本研究では, hES/iPS細胞からの高効率的内耳耳胞様細胞誘導系を用いてヒト内耳細胞(感覚上皮前駆細胞, 有毛細胞, 支持細胞など)をin vitroで大量調整し, 創薬に直結する薬剤スクリーニング系を構築した。その結果, 新規有毛細胞分化誘導剤, 外らせん溝細胞誘導液性因子, 蝸牛感覚上皮の幹細胞性維持因子, 有毛細胞の成熟化因子, Pendred症候群蝸牛外らせん溝細胞の細胞死を保護する薬剤の推定最小薬理量算出と薬剤の量反応効果の個人差の定量を行った。
Since the inner ear is located deep inside the temporal bone and its biopsy causes severe hearing loss, studies using human inner ear cells have not been performed so far. In this study, we developed drug screening systems using a highly efficient inner otocyst-like cell induction method from hES/iPS cells. From the study, we obtained new hair cell inducers and a humoral factor for the induction of outer sulcus cells, defined a molecular mechanism of the maintenance of stemness in the cochlear progenitors and a mechanism for the maturation of hair cells. Also, we obtained the MABEL of rapamycin on the prevention of apoptosis of the outer sulcus cells of Pendred syndrome/ DFNB4.
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研究種目 : 挑戦的萌芽研究
研究期間 : 2014～2016
課題番号 : 26670748
研究分野 : 感音難聴
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