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Researches using iPS cells on intractable respiratory diseases to elucidate their pathogenesis and develop novel therapy.

Research Project

Project/Area Number 22249031
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionKyoto University

Principal Investigator

MISHIMA MICHIAKI  京都大学, 医学(系)研究科(研究院), 教授 (60190625)

Co-Investigator(Kenkyū-buntansha) OGAWA Emiko  滋賀医科大学, 学内共同利用施設等, 講師 (00378671)
SEYAMA Kuniaki  順天堂大学, 医学部, 准教授 (10226681)
HANDA Tomohiro  京都大学, 医学研究科, 助教 (10432395)
HIRAI Toyohiro  京都大学, 医学研究科, 准教授 (20359805)
ITO Isao  京都大学, 医学研究科, 特定病院助教 (40447975)
MURO Shigeo  京都大学, 医学研究科, 講師 (60344454)
MATSUMOTO Hisako  京都大学, 医学研究科, 助教 (60359809)
HEIKE Toshio  京都大学, 医学研究科, 教授 (90190173)
CHIN Kazuo  京都大学, 医学研究科, 特定教授 (90197640)
星野 勇馬  京都大学, 医学(系)研究科(研究院), 助教 (00378746)
新実 彰男  京都大学, 医学研究科, 准教授 (30252513)
Project Period (FY) 2010-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥46,670,000 (Direct Cost: ¥35,900,000、Indirect Cost: ¥10,770,000)
Fiscal Year 2014: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
Fiscal Year 2013: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
Fiscal Year 2012: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
Fiscal Year 2011: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
Fiscal Year 2010: ¥10,270,000 (Direct Cost: ¥7,900,000、Indirect Cost: ¥2,370,000)
KeywordsiPS細胞 / ES細胞 / II型肺胞上皮細胞 / surfactant protein C / carboxypeptidase M / 3次元培養 / Hermansky-Pudlak 症候群 / 嚢胞性線維症 / 疾患特異iPS / 肺胞上皮細胞 / 特発性間質性肺炎 / 若年性肺気腫 / リンパ脈管筋腫症 / 疾患特異的iPS / I型肺胞上皮細胞 / 分化誘導 / Birt-Hogg-Dube症候群
Outline of Final Research Achievements

In this project, we focused on establishing methods to induce alveolar type II cells from human iPS/ES cells. First, in the stepwise induction of NKX2-1-positive “ventralized” anterior foregut endoderm cells (VAFECs), we identified carboxypeptidase M (CPM) as a surface marker of the cells and fetal human and murine lungs. CPM-positive cells were successfully purified from VAFECs. To overcome difficulty in determining surfactant protein-C positive cells, we generated SFTPC-GFP reporter human iPS cells. Using the reporter cells, a three-dimensional co-culture with fetal human lung fibroblasts was performed. CPM-positive cells purified from VAFECs differentiated into GFP-positive alveolar type II cells within spheroid structures, showing lamellar body-like structures by electron microscopy.
We generated disease specific human iPS cells of Hermansky-Pudlak syndrome and cystic fibrosis.

Report

(6 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (26 results)

All 2015 2014 2013 2012 2011 2010 Other

All Journal Article (16 results) (of which Peer Reviewed: 16 results,  Open Access: 5 results) Presentation (8 results) (of which Invited: 2 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 1 results)

  • [Journal Article] A toll-like receptor 3 single nucleotide polymorphism in Japanese patients with sarcoidosis.2015

    • Author(s)
      Ikezoe K, Handa T, Tanizawa K, Kubo T, Ito I, Sokai A, Nakatsuka Y, Nagai S, Izumi T, Mishima M
    • Journal Title

      Tissue Antigens

      Volume: 85 Issue: 3 Pages: 204-208

    • DOI

      10.1111/tan.12535

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Emphysema and airway disease affect within-breath changes in respiratory resistance in COPD patients.2015

    • Author(s)
      Hasegawa K, Sato S, Tanimura K, Fuseya Y, Uemasu K, Sato A, Hirai T, Mishima M, Muro S
    • Journal Title

      Respirology

      Volume: - Issue: 5 Pages: 775-81

    • DOI

      10.1111/resp.12535

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Neutrophil gelatinase-associated lipocalin in idiopathic pulmonary fibrosis.2014

    • Author(s)
      Ikezoe K, Handa T, Mori K, Watanabe K, Tanizawa K, Aihara K, Tsuruyama T, Miyagawa-Hayashino A, Sokai A, Kubo T, Muro S, Nagai S, Hirai T, Chin K, Mishima M
    • Journal Title

      Eur Respir J

      Volume: 43 Issue: 6 Pages: 1807-1809

    • DOI

      10.1183/09031936.00192613

    • Related Report
      2014 Annual Research Report
    • 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

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] p38 mitogen-activated protein kinase determines the susceptibility to cigarette smoke-induced emphysema in mice.2014

    • Author(s)
      Marumo S, Hoshino Y, Kiyokawa H, Tanabe N, Sato A, Ogawa E, Muro S, Hirai T, Mishima M
    • Journal Title

      BMC Pulm Med

      Volume: 14 Issue: 1

    • DOI

      10.1186/1471-2466-14-79

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Osteopontin and periostin are associated with a 20-year decline of pulmonary function in patients with asthma.2014

    • Author(s)
      Kanemitsu Y, Ito I, Niimi A, Izuhara K, Ohta S, Ono J, Iwata T, Matsumoto H, Mishima M
    • Journal Title

      Am J Respir Crit Care Med

      Volume: 190 Issue: 4 Pages: 472-474

    • DOI

      10.1164/rccm.201403-0562le

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Generation of alveolar epithelial spheroids via isolated progenitor cells from human pluripotent stem cells.2014

    • Author(s)
      Gotoh S, Ito I, Nagasaki T, Yamamoto Y, Konishi S, Korogi Y, Matsumoto H, Muro S, Hirai T, Funato M, Mae S, Toyoda T, Sato-Otsubo A, Ogawa S, Osafune K, Mishima M
    • Journal Title

      Stem Cell Reports

      Volume: 3 Issue: 3 Pages: 394-403

    • DOI

      10.1016/j.stemcr.2014.07.005

    • NAID

      120005477388

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Neutrophil gelatinase-associated lipocalin in idiopathic pulmonary fibrosis2014

    • Author(s)
      Ikezoe K, Mishima M, et al.
    • Journal Title

      Eur Respir J

      Volume: 未定

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Thioredoxin-1 protects against neutrophilic inflammation and emphysema progression in a mouse model of chronic obstructive pulmonary disease2013

    • Author(s)
      Tanabe N, Mishima M,et al
    • Journal Title

      Plos One

      Volume: なし Issue: 11 Pages: e79016-e79016

    • DOI

      10.1371/journal.pone.0079016

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Increased periostin associates with greater airflow limitation in patients receiving inhaled corticosteroids2013

    • Author(s)
      Kanemitsu Y, Mishima M,et al.
    • Journal Title

      J Allergy Clin Immunol

      Volume: 132 Issue: 2 Pages: 305-312

    • DOI

      10.1016/j.jaci.2013.04.050

    • NAID

      120005342661

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Computed tomography assessment of pharmacological lung volume reduction induced by bronchodilators in COPD2012

    • Author(s)
      Tanabe N, Muro S, Oguma T, Sato S, Kiyokawa H, Takahashi T, Kudo M, Kinose D, Kubo T, Hoshino Y, Ogawa E, Hirai T, Mishima M. COPD
    • Journal Title

      COPD

      Volume: 9 Issue: 4 Pages: 1-8

    • DOI

      10.3109/15412555.2012.674986

    • Related Report
      2012 Annual Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Association between vascular-poor area of primary tumors and epidermal growth factor receptor gene status in advanced lung adenocarcinoma2012

    • Author(s)
      Togashi Y, Kubo T, et al.
    • Journal Title

      Med Oncol

      Volume: なし Issue: 5 Pages: 3169-3175

    • DOI

      10.1007/s12032-012-0235-7

    • Related Report
      2012 Annual Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Increase in circulating endothelial progenitor cells predicts response in patients with advanced non-small-cell lung cancer2012

    • Author(s)
      im YH, Ichiyama S, Mishima M, et al
    • Journal Title

      Cancer Sci

      Volume: 1 Issue: 6 Pages: 24-30

    • DOI

      10.1111/j.1349-7006.2012.02249.x

    • Related Report
      2012 Annual Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] To authors reply. invasive mechanical ventilation in patients with idiopathic pulmonary fibrosis or idiopathic non-specific interstitial pneumonia2011

    • Author(s)
      Tomii K, Tachikawa R, Chin K, Murase K, Handa T, Mishima M, Ishihara K
    • Journal Title

      Intern Med

      Volume: 50(2) Pages: 175-175

    • NAID

      130000413224

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Association of the transforming growth factor β1 promoter polymorphism, C-509T, with smoking status and survival in advanced non-small cell lung cancer. Oncol Rep2011

    • Author(s)
      Togashi Y, Masago K, Fujita S, Kim YH, Sakamori Y, Hatachi Y,Fukuhara A, Nagai H, Mio T, Mishima M
    • Journal Title

      Oncol Rep

      Volume: 25(2) Pages: 377-382

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genetic polymorphisms in the endothelial nitric oxide synthase gene correlate with overall survival in advanced non-small-cell lung cancer patients treated with platinum-based doublet chemotherapy2010

    • Author(s)
      Fujita S, Masago K, Hatachi Y, Fukuhara A, Hata A, Kaji R, Kim YH, Mio T, Mishima M, Katakami N
    • Journal Title

      BMC Med Genet

      Volume: 11 Pages: 167-167

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] 遺伝性呼吸器疾患の疾患特異的iPS細胞樹立2015

    • Author(s)
      後藤慎平、伊藤功朗、三嶋理晃 他
    • Organizer
      第55回日本呼吸器学会総会
    • Place of Presentation
      東京
    • Year and Date
      2015-04-17 – 2015-04-19
    • Related Report
      2014 Annual Research Report
  • [Presentation] 会長講演:COPD(慢性閉塞性肺疾患)の研究をふり返って~デジタル画像解析からiPS細胞研究まで~2015

    • Author(s)
      三嶋理晃
    • Organizer
      第112回日本内科学会講演会
    • Place of Presentation
      京都
    • Year and Date
      2015-04-10 – 2015-04-12
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Clinical application of iPS cell in the respiratory field including COPD and asthma.2014

    • Author(s)
      Michiaki Mishima
    • Organizer
      Asian Pacific Society of Respirology
    • Place of Presentation
      Bali, Indonesia
    • Year and Date
      2014-11-13 – 2014-11-16
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Generation of alveolar epithelial cells from human pluripotent stem cells.2014

    • Author(s)
      Shimpei Gotoh, Isao Ito, Tadao Nagasaki, Yuki Yamamoto, Satoshi Konishi, Yohei Korogi, Hisako Matsumoto, Shigeo Muro, Toyohiro Hirai, Michinori Funato, Shin-Ichi Mae, Taro Toyoda, Aiko Sato-Otsubo, Seishi Ogawa, Kenji Osafune, Michiaki Mishima
    • Organizer
      ISSCR
    • Place of Presentation
      Vancouver, Canada
    • Year and Date
      2014-06-18 – 2014-06-21
    • Related Report
      2014 Annual Research Report
  • [Presentation] Clinical problems in COPD2012

    • Author(s)
      三嶋 理晃
    • Organizer
      第52回日本呼吸器学会学術講演会
    • Place of Presentation
      神戸コンベンションセンター
    • Related Report
      2012 Annual Research Report
  • [Presentation] 病型分類の臨床的意義2011

    • Author(s)
      三嶋理晃
    • Organizer
      第51回呼吸器学会総会シンポジウム
    • Place of Presentation
      東京国際フォーラム
    • Year and Date
      2011-04-22
    • Related Report
      2011 Annual Research Report
  • [Presentation] Mechanisms of Enhanced Ca2+ Oscillation Frequency by Interleukin-13 in Airway Smooth Muscle Cells2010

    • Author(s)
      H.Matsumoto, Y.Hirata, K.Otsuka, A.Niimi, I.Ito, T.Iwata, E.Ogawa, S.Muro, H.Sakai, K.Chin, Y.Oku, M.Mishima
    • Organizer
      ATS2010
    • Place of Presentation
      Colorado
    • Related Report
      2010 Annual Research Report
  • [Presentation] ヒトiPS細胞から肺胞上皮細胞への分化誘導

    • Author(s)
      後藤 慎平
    • Organizer
      第53回日本呼吸器学会総会
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
  • [Patent(Industrial Property Rights)] 肺胞上皮前駆細胞の誘導方法2014

    • 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
    • Filing Date
      2014-04-14
    • Related Report
      2014 Annual Research Report
    • 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
    • Filing Date
      2013-04-12
    • Related Report
      2013 Annual Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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