小括

63

64 第四章 総括

本研究では、ヒトおよびカニクイザル iPS 細胞から腸管オルガノイドへの分 化促進に有用である低分子化合物の組み合わせを新たに見出すことができた。

また、EZSPHERE plateと浮遊培養法により、均一な腸管オルガノイドの培養に

成功した。この方法によって作製した腸管オルガノイドは、機能的なタイトジャ ンクション、排出トランスポーターの輸送機能に加え、薬物代謝酵素活性および 誘導能を有するなど、腸管に特徴的な薬物動態学的機能を有していることが明 らかとなった。さらに、IBD、特にクローン病モデルや線維化モデルをそれぞれ 疾患の要因となっている主要なサイトカインを添加することで作製でき、これ ら病態に対する薬物スクリーニング系としても有用である可能性が示唆された。

65 謝 辞

本研究の遂行に際し、終始御懇篤な御指導、御鞭撻を賜り、また本論文の御校 閲を頂きました名古屋市立大学大学院薬学研究科臨床薬学分野 松永 民秀 教 授に深甚なる謝意を表します。

本研究の遂行に際し、格別の御配慮と御激励を賜りました名古屋市立大学大 学院薬学研究科臨床薬学分野 鈴木 匡 教授に深甚なる謝意を表します。

本研究の遂行に際し、終始御懇篤な御指導、御鞭撻を賜り、また本論文の御校 閲を頂きました名古屋市立大学大学院薬学研究科臨床薬学分野 岩尾 岳洋 准 教授に深甚なる謝意を表します。

本論文作成にあたり、種々の有益な御助言と御校閲を賜りました、名古屋市立 大学大学院薬学研究科医薬品安全性評価学分野 頭金 正博 教授、名古屋市立大 学大学院薬学研究科生体超分子システム解析学分野 平嶋 尚英 教授ならびに 名古屋市立大学大学院薬学研究科薬物動態制御学分野 湯浅 博昭 教授に深謝 いたします。

本研究の遂行に際し、有益な御助言とご協力を賜りました名古屋市立大学大 学院薬学研究科臨床薬学分野 菊池 千草 講師ならびに名古屋市立大学大学院 薬学研究科臨床薬学分野 坡下 真大 講師に厚く御礼申し上げます。

本研究を遂行するにあたり、ヒトiPS 細胞株 (Windy) をご供与頂きました国 立成育医療研究センター研究所 阿久津 英憲 博士、宮川 世志幸 博士、大喜多 肇 博士、清河 信敬 博士、豊田 雅士 博士ならびに梅澤 明弘 博士に謹んで御 礼申し上げます。

本研究を遂行するにあたり、透過型電子顕微鏡観察において、サンプル調整や 観察について、非常に丁寧なご指導を頂いた名古屋市立大学医学部共同研究セ ンター 高瀬 弘嗣 先生に謹んで御礼申し上げます。

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