Challenge to search for lung progenitor cells and to develop alveolar type II cells from human iPS cells

• Project/Area Number: 23591146
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Kyoto University
• Principal Investigator: ITO Isao 京都大学, 医学(系)研究科(研究院), 助教 (40447975)
• Co-Investigator(Kenkyū-buntansha): OSAFUNE Kenji 京都大学, 学内共同利用施設等, 准教授 (80502947) ; NIIMI Akio 名古屋市立大学, 医学(系)研究科(研究院), 教授 (30252513) ; MISHIMA Michiaki 京都大学, 医学(系)研究科(研究院), 教授 (60190625) ; MURO Shigeo 京都大学, 医学(系)研究科(研究院), 講師 (60344454)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: iPS細胞 / 肺胞上皮細胞 / 組織幹細胞 / サーファクタント / レポーター細胞 / SPC / NKX2.1 / ES細胞 / SP-C / サーファクタントプロテインC / II型肺胞上皮細胞 / 前腸細胞 / FOXA2 / SOX2 / ヒトiPS細胞

Research Abstract

In this study grant, we have established original methods to develop iPS cells into alveolar cells. The induced population expressed marker proteins such as surfactant protein-C, which are required for alveolar type II cells. In the process of developing induction methods, we have identified a surface marker for NKX2.1 positive cells. The marker enables us to isolate these cells and cells positive for this marker developed into a range of airway and alveolar epithelial cells. Our findings would contribute much for further research on inducing alveolar cell population from undiffereniated cells.

Research Products

• [Journal Article] Osteopontin and periostin associate with a 20-year decline of pulmonary function in asthmatics (2014)
  • Author(s): Kanemitsu Y, Ito I, Niimi A, Izuhara K, Ohta S, Ono J, IwataT, Matsumoto H, Mishima M
  • Journal Title: Am J Respir Crit Care Med Volume: (accepted)
• [Journal Article] Isolation of drug-resistant pathogens does not always require use of broad-spectrum antibiotics in pneumonia (2014)
  • Author(s): Ito I, Mishima M
  • Journal Title: Am J Respir Crit Care Med Volume: 189 Pages: 756-7
• [Journal Article] Prevalence and clinical relevance of allergic rhinitis in patients with classic asthma and cough variant asthma (2014)
  • Author(s): Tajiri T, Niimi A, Matsumoto H, Ito I, Oguma T, Otsuka K, Takeda T, Nakaji H, Inoue H, Iwata T, Nagasaki T, Mishima M
  • Journal Title: Respiration Volume: 87 Pages: 211-8
• [Journal Article] Isolation of drug-resistant pathogens does not always require use of broad-spectrum antibiotics in pneumonia. (2014)
  • Author(s): Ito I, et al.
  • Journal Title: Am J Respir Crit Care Med Volume: 189 Issue: 6 Pages: 756-757
  • DOI: 10.1164/rccm.201312-2162le
  • Peer Reviewed
• [Journal Article] Integrating longitudinal information on pulmonary function and inflammation using asthma phenotypes. (2014)
  • Author(s): Nagasaki T, Matsumoto H, Kanemitsu Y, Izuhara K, Tohda Y, Kita H, Horiguchi T, Kuwabara K, Tomii K, Otsuka K, Fujimura M, Ohkura N, Tomita K, Yokoyama A, Ohnishi H, Nakano Y, Oguma T, Hozawa S, Ito I, Oguma T, Inoue H, Tajiri T, Iwata T, Izuhara Y, Ono J, Ohta S, Yokoyama T, Niimi A, Mishima M
  • Journal Title: J Allergy Clin Immunol Volume: 133 Issue: 5 Pages: 1474-1477
  • DOI: 10.1016/j.jaci.2013.12.1084
  • Peer Reviewed / Open Access
• [Journal Article] Prevalence and clinical relevance of allergic rhinitis in patients with classic asthma and cough variant asthma. (2014)
  • Author(s): Tajiri T, Niimi A, Matsumoto H, Ito I, Oguma T, Otsuka K, Takeda T, Nakaji H, Inoue H, Iwata T, Nagasaki T, Mishima M.
  • Journal Title: Respiration. Volume: 87 Issue: 3 Pages: 211-8
  • DOI: 10.1159/000355706
  • Peer Reviewed
• [Journal Article] Association of eosinophilic inflammation with FKBP51 expression in sputum cells in asthma (2013)
  • Author(s): Tajiri T, Matsumoto H, Niimi A, Ito I, Oguma T, Nakaji H, Inoue H, Iwata T, Nagasaki T, Kanemitsu Y, Petrova G, Mishima M
  • Journal Title: PLoS One Volume: 8
  • NAID: 120005296109
• [Journal Article] Anticholinergic agents result in weaker and shorter suppression of uterine contractility compared with intestinal motion : time course observation with cine MRI (2013)
  • Author(s): Daido S, Nakai A, Kido A, Okada T, Kamae T, Fujimoto K, Ito I, Togashi K
  • Journal Title: J Magn Reson Imaging Volume: 38 Pages: 1196-202
• [Journal Article] Smoking attenuates the age-related decrease in IgE levels and maintains eosinophilic inflammation (2013)
  • Author(s): Nagasaki T, Matsumoto H, Nakaji H, Niimi A, Ito I, Oguma T, Muro S, Inoue H, Iwata T, Tajiri T, Kanemitsu Y, Mishima M
  • Journal Title: Clin Exp Allergy Volume: 43 Pages: 608-15
• [Journal Article] Interferon regulatory factor 5 polymorphisms in sarcoidosis (2013)
  • Author(s): Tanizawa K, Handa T, Nagai S, Sato H, Yamada R, Ito I, Kubo T, Ito Y, Watanabe K, Aihara K, Ikezoe K, Mishima M, Izumi T
  • Journal Title: Mod Rheumatol Volume: 23 Pages: 1158-65
• [Journal Article] Effects of 24-week add-on treatment with ciclesonide and montelukast on small airways inflammation in asthma (2013)
  • Author(s): Nakaji H, Petrova G, Matsumoto H, Iwata T, Ito I, Oguma T, Inoue H, Tajiri T, Nagasaki T, Kanemitsu Y, Niimi A, Mishima M
  • Journal Title: Ann Allergy Asthma Immunol Volume: 110 Pages: 198-203
  • NAID: 120005244569
• [Journal Article] Optimizing cine MRI for uterine peristalsis : A comparison of three different single shot fast spin echo techniques (2013)
  • Author(s): Nakai A, Reinhold C, Noel P, Kido A, Rafatzand K, Ito I, Togashi K
  • Journal Title: J Magn Reson Imaging Volume: 38 Pages: 161-7
• [Journal Article] ssociation of eosinophilic inflammation with FKBP51 expression in sputum cells in asthma. (2013)
  • Author(s): Tajiri T, Matsumoto H, Niimi A, Ito I, Oguma T, Nakaji H, Inoue H, Iwata T, Nagasaki T, Kanemitsu Y, Petrova G, Mishima M.
  • Journal Title: PLoS One Volume: 8 Issue: 6 Pages: e65284-e65284
  • DOI: 10.1371/journal.pone.0065284
  • Peer Reviewed
• [Journal Article] Effects of 24-week add-on treatment with ciclesonide and montelukast on small airways inflammation in asthma. (2013)
  • Author(s): Nakaji H, Petrova G, Matsumoto H, Iwata T, Ito I, Oguma T, Inoue H, Tajiri T, Nagasaki T, Kanemitsu Y, Niimi A, Mishima M.
  • Journal Title: Ann Allergy Asthma Immunol. Volume: 110 Issue: 3 Pages: 198-203
  • DOI: 10.1016/j.anai.2012.12.016
  • NAID: 120005244569
  • Peer Reviewed
• [Journal Article] Nitric oxide enhances pemetrexed cytotoxicity via NO-cGMP signaling in lung adenocarcinoma cells in vitro and in vivo (2013)
  • Author(s): Nagai H, Yasuda H, Hatachi Y, Xue D, Sasaki T, Yamaya M, Sakamori Y, Togashi Y, Masago K, Ito I, Kim YH, Mio T, Mishima M.
  • Journal Title: Int J Oncology Volume: 41 Pages: 3271-3278
  • DOI: 10.3892/ijo.2012.1461
  • Peer Reviewed
• [Journal Article] Pulmonary hemorrhage induced by epileptic seizure (2012)
  • Author(s): Azuma M, Ito I, Matsumoto R, Hirai T, Mishima M
  • Journal Title: Heart Lung Volume: 40 Pages: 290-3
  • NAID: 120004140499
• [Journal Article] Clinical features and risk factors of tuberculosis in living-donor liver transplant recipients (2012)
  • Author(s): Imai S, Ito Y, Hirai T, Imai H, Ito I, Maekawa K, Chin K, Ichiyama S, Uemoto S, Mishima M
  • Journal Title: Transpl Infect Dis Volume: 14 Pages: 9-16
• [Journal Article] Sputum YKL-40 Levels and Pathophysiology of Asthma and Chronic Obstructive Pulmonary Disease (2012)
  • Author(s): Otsuka K, Matsumoto H, Niimi A, Muro S, Ito I, Takeda T, Terada K, Yamaguchi M, Matsuoka H, Jinnai M, Oguma T, Nakaji H, Inoue H, Tajiri T, Iwata T, Chin K, Mishima M
  • Journal Title: Respiration Volume: 83 Pages: 507-19
  • NAID: 120004397864
• [Journal Article] Smoking attenuates the age-related decrease in IgE levels and maintains eosinophilic inflammation (2012)
  • Author(s): Nagasaki T, Matsumoto H, Nakaji H, Niimi A, Ito I
  • Journal Title: Clin Exp Allergy Volume: なし
  • Peer Reviewed
• [Journal Article] A CD40 single nucleotide polymorphis affects the lymphocyte profiles in the bronchoalveolar lavage of Japanese patients with sarcoidosis (2011)
  • Author(s): Tanizawa K, Handa T, Nagai S, Ito I, Takeshi K, Ito Y, Watanabe K, Aihara K, Mishima M, Izumi T
  • Journal Title: Tissue Antigens Volume: 78 Pages: 442-5
• [Journal Article] Toyama Asian Desert Dust and Asthma Study Team. Desert-dust exposure is associated with increased risk of asthma hospitalization in children (2010)
  • Author(s): Kanatani KT, Ito I, Al-Delaimy WK, Adachi Y, Mathews WC, Ramsdell JW
  • Journal Title: Am J Respir Crit Care Med Volume: 182 Pages: 1475-81
• [Journal Article] Tazobactam/piperacillin for moderate-to-severe pneumonia in patients with risk for aspiration : comparison with imipenem/cilastatin (2010)
  • Author(s): Ito I, Kadowaki S, Tanabe N, Haruna A, Kase M, Yasutomo Y, Tsukino M, Nakai A, Matsumoto H, Niimi A, Chin K, Ichiyama S, Mishima M
  • Journal Title: Pulm Pharmacol Ther Volume: 23 Pages: 403-10
  • NAID: 120002484950
• [Presentation] Generation of alveolar epithelial cells from human pluripotent stem cells (2014)
  • Author(s): Gotoh S, Ito I, et al
  • Organizer: accepted for presentation in ISSCR 2014 and given a Travel Award
• [Presentation] ヒトiPS細胞から肺胞上皮細胞への分化誘導 (2013)
  • Author(s): 後藤慎平、伊藤功朗, 他
  • Organizer: 第53回日本呼吸器学会総会
  • Year and Date: 2013-04-21
• [Presentation] ヒトiPS細胞から肺胞上皮細胞への分化誘導 (2013)
  • Author(s): 後藤慎平
  • Organizer: 第５３回日本呼吸器学会総会
  • Place of Presentation: 東京
• [Patent(Industrial Property Rights)] 肺胞上皮前駆細胞の誘導方法 (2013)
  • Inventor(s): 長船健二, 後藤慎平, 伊藤功朗, 三嶋理晃
  • Industrial Property Rights Holder: 国立大学法人京都大学
  • Industrial Property Number: 2013-084034
  • Filing Date: 2013-04-12
  • Overseas
• [Patent(Industrial Property Rights)] 肺胞上皮前駆細胞の誘導 (2013)
  • Inventor(s): 長船健二、後藤慎平、伊藤功朗、三嶋理晃
  • Industrial Property Rights Holder: 国立大学法人京都大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2013-084034
  • Filing Date: 2013-04-19