Development of functional bronchial ciliated cell sheet from human iPS cells

• Project/Area Number: 17H04183
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Kyoto University
• Principal Investigator: Ito Isao 京都大学, 医学研究科, 講師 (40447975)
• Co-Investigator(Kenkyū-buntansha): オケヨ ケネディオモンディ 京都大学, ウイルス・再生医科学研究所, 講師 (10634652) ; 小寺 秀俊 国立研究開発法人理化学研究所, 科技ハブ産連本部, 本部長 (20252471) ; 鷲津 正夫 東京大学, 大学院工学系研究科(工学部), 教授 (10201162)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥12,610,000 (Direct Cost: ¥9,700,000、Indirect Cost: ¥2,910,000); Fiscal Year 2019: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2018: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2017: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
• Keywords: 未分化細胞 / メッシュシート / 気液界面培養 / 培養 / 肺胞上皮 / iPS細胞 / 組織幹細胞 / マイクロメッシュ / マイクロ流体デバイス / 肺胞上皮細胞 / 血管内皮細胞 / メッシュ / 二層構造 / 再生医学 / ナノバイオ / 発生・分化 / 内科 / マイクロ・デバイス / マイクロ・ナノデバイス

Outline of Final Research Achievements

We tried to establish a culture system for future application of bronchial epithelial regeneration using bronchial epithelial cell sheet. Although we first planned to achieve such sheet with induced cilliary bronchial epithelial cells from human iPS cells, there turned out to be multiple uncontrolled problems. Then, we used mouse lung epithelial cells derived from mouse lungs. As a scaffold for cell culture, mesh sheet of a variety of hole sizes were used and also we developed ultra-thin membrane-spread mesh sheet. As a basement scaffold, the sheet with ultra-thin membrane turned out to be appropriate to culture the cells. the undifferentiated cells from mouse lung cell expanded and developed into bronchial epithelial cells.

Academic Significance and Societal Importance of the Research Achievements

機能的な気道上皮細胞シートの開発につながり，気管欠損患者に対する細胞移植への応用展開が期待できる。また，本システムは稀少疾患（例えば原発性繊毛運動不全症）のみならず様々なcommon diseaseの病態研究（例えば後天性気管支拡張症）の病態を模倣することができるため，これらの疾患病理学的な研究のほか，薬剤スクリーニングに応用することができる可能性がある。

Research Products

• [Journal Article] The utility of serial procalcitonin measurements in addition to pneumonia severity scores in hospitalized community-acquired pneumonia: A multicentre, prospective study. (2020)
  • Author(s): Ito A, Ito I, Inoue D, Marumo S, Ueda T, Nakagawa H, Taki M, Nakagawa A, Tatsumi S, Nishimura T, Shiota T, Ishida T.
  • Journal Title: Int J Infect Dis Volume: 92 Pages: 228-233
  • DOI: 10.1016/j.ijid.2020.01.018
  • Peer Reviewed
• [Journal Article] Cefepime vs. meropenem for moderate-to-severe pneumonia in patients at risk for aspiration: An open-label, randomized study. (2020)
  • Author(s): Oi I, Ito I, Tanabe N, Konishi S, Hamao N, Yasutomo Y, Kadowaki S, Hirai T.
  • Journal Title: J Infect Chemother Volume: 26 Issue: 2 Pages: 181-187
  • DOI: 10.1016/j.jiac.2019.08.005
  • Peer Reviewed
• [Journal Article] Induction of airway remodeling and persistent cough by repeated citric acid exposure in a guinea pig cough model. (2019)
  • Author(s): Cui S, Ito I, Nakaji H, Iwata T, Matsumoto H, Oguma T, Tajiri T, Nagasaki T, Kanemitsu Y, Izuhara H, Mishima M, Niimi A.
  • Journal Title: Respir Physiol Neurobiol. Volume: 263 Pages: 1-8
  • DOI: 10.1016/j.resp.2019.02.002
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] In?Vitro Disease Modeling of Hermansky-Pudlak Syndrome Type 2?Using Human Induced Pluripotent Stem Cell-Derived Alveolar Organoids (2019)
  • Author(s): Korogi Yohei、Gotoh Shimpei、Ikeo Satoshi、Yamamoto Yuki、Sone Naoyuki、Tamai Koji、Konishi Satoshi、Nagasaki Tadao、Matsumoto Hisako、Ito Isao、Chen-Yoshikawa Toyofumi F.、Date Hiroshi、Hagiwara Masatoshi、Asaka Isao、Hotta Akitsu、Mishima Michiaki、Hirai Toyohiro
  • Journal Title: Stem Cell Reports Volume: 12 Issue: 3 Pages: 431-440
  • DOI: 10.1016/j.stemcr.2019.01.014
  • Peer Reviewed / Open Access