Cell-based therapy in lung regenerative medicine using adipose tissue-derived stem cell and induced pluripotent stem cell

• Project/Area Number: 26293316
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Respiratory surgery
• Research Institution: Osaka University
• Principal Investigator: Okumura Meinoshin 大阪大学, 医学(系)研究科(研究院), 教授 (40252647)
• Co-Investigator(Kenkyū-buntansha): 南 正人 大阪大学, 医学部附属病院, 准教授 (10240847) ; 井上 匡美 京都府立医科大学, 医学(系)研究科(研究院), 教授 (10379232) ; 川村 知裕 大阪大学, 医学(系)研究科(研究院), 助教 (30528675) ; 舟木 壮一郎 大阪大学, 医学(系)研究科(研究院), 助教 (50464251) ; 松浦 成昭 大阪大学, 医学(系)研究科(研究院), 特任教授 (70190402) ; 新谷 康 大阪大学, 医学(系)研究科(研究院), 准教授 (90572983) ; 中桐 伴行 大阪大学, 医学(系)研究科(研究院), 研究員 (70528710)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥15,860,000 (Direct Cost: ¥12,200,000、Indirect Cost: ¥3,660,000); Fiscal Year 2016: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2014: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
• Keywords: 肺再生 / 幹細胞 / 脂肪幹細胞 / 人工多機能性幹細胞 / 慢性閉塞性肺疾患 / iPS細胞 / アディポネクチン / 肺気腫 / HGF / PGI2

Outline of Final Research Achievements

Chronic obstructive pulmonary disease (COPD), a progressive lung disease. This study was designed to develop the therapeutic solution against COPD by the cell therapy.
We used the representative mice model of COPD. The adipose tissue-derived stem cell (ADSCs), , administered intravenously, and trans-bronchially. The ADSCs accumulated the damaged area and significantly inhibited deterioration of the lung compliance and histologic changes. We also focused on the induced pluripotent stem (iPS) cell as a source of supply of lung epithelial cell. To prepare the type2 alveolar cells, we investigated the general methods of differentiation the iPS cells. The differentiated iPS cells were transplanted into COPD model mice and improved lung function.Our data indicated that the administration of ADSCs and iPS cells improved the emphysema histologically and functionally.

Research Products

• [Journal Article] C-type natriuretic peptide ameliorates pulmonary fibrosis by acting on lung fibroblasts in mice. (2016)
  • Author(s): Kimura T, Nojiri T, Hino J, Hosoda H, Miura K, Shintani Y, Inoue M, Zenitani M, Takabatake H, Miyazato M, Okumura M, Kangawa K.
  • Journal Title: Respiratory research Volume: 17 Issue: 1 Pages: 19-19
  • DOI: 10.1186/s12931-016-0335-6
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Carnosol Is a Potent Lung Protective Agent: Experimental Study on Mice. (2015)
  • Author(s): Kawamura T,Momozane T, Funaki S, Shintani Y, Inoue M, Minami M, Sugimura K, Iida O, Fuchino H, Kawahara N, Takemori H, Okumura M
  • Journal Title: Transplant Procedings Volume: 47 Issue: 6 Pages: 1657-61
  • DOI: 10.1016/j.transproceed.2015.05.004
  • Peer Reviewed
• [Journal Article] C-type natriuretic peptide attenuates lipopolysaccharide-induced acute lung injury in mice (2015)
  • Author(s): Kimura T, Nojiri T, Hosoda H, Ishikane S, Shintani Y, Inoue M, Miyazato M, Okumura M, Kangawa K
  • Journal Title: J Surg Res Volume: 194 Issue: 2 Pages: 631-637
  • DOI: 10.1016/j.jss.2014.11.023
  • Peer Reviewed / Open Access
• [Journal Article] Protective effects of C-type natriuretic peptide on cisplatin-induced nephrotoxicity in mice (2015)
  • Author(s): Kimura, T., Nojiri, T., Hosoda, H., Ishikane, S., Shintani, Y., Inoue, M., Miyazato, M., Okumura, M., Kangawa, K.
  • Journal Title: Cancer Chemotherapy and Pharmacology Volume: 75(5) Issue: 5 Pages: 1057-1063
  • DOI: 10.1007/s00280-015-2734-7
  • Peer Reviewed / Open Access
• [Journal Article] Exacerbation of bleomycin-induced injury by lipopolysaccharide in mice: establishment of a mouse model for acute exacerbation of interstitial lung diseases. (2015)
  • Author(s): Kimura T, Nojiri T, Hosoda H, Shintani Y, Inoue M, Miyazato M, Okumura M, Kangawa K.
  • Journal Title: European journal of cardio-thoracic surgery Volume: 48 Issue: 4 Pages: e85-e91
  • DOI: 10.1093/ejcts/ezv261
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Clinical usefulness of free subcutaneous fat pad for reduction of intraoperative air leakage during thoracoscopic pulmonary resection in lung cancer cases. (2014)
  • Author(s): Shintani Y, Inoue M, Funaki S, Kawamura T, Minami M, Okumura M.
  • Journal Title: Surg Endosc. Volume: Epub
  • Peer Reviewed
• [Journal Article] Atrial natriuretic peptide inhibits lipopolysaccharide-induced acute lung injury (2014)
  • Author(s): Nojiri T, Hosoda H, Tokudome T, Miura K, Ishikane S, Kimura T, Shintani Y, Inoue M, Sawabata N, Miyazato M, Okumura M, Kangawa K
  • Journal Title: Pulm Pharmacol Ther Volume: 29 Issue: 1 Pages: 24-30
  • DOI: 10.1016/j.pupt.2014.01.003
  • Peer Reviewed / Open Access
• [Presentation] 難治性肺疾患に対する肺再生治療 (2017)
  • Author(s): 舟木壮一郎、新谷康、川村知裕、神崎隆、南正人、酒井芳紀、宮川繁、澤芳樹、奥村明之進
  • Organizer: 第57回日本呼吸器学会総会
  • Place of Presentation: 東京（東京国際フォーラム）
  • Year and Date: 2017-04-21
  • Invited
• [Presentation] 肺障害治癒過程における脂肪組織幹細胞の役割 (2017)
  • Author(s): 福井絵里子、新谷康、桃實徹、神崎隆、川村知裕、舟木壮一郎、南正人、奥村明之進
  • Organizer: 第16回日本再生医療学会総会
  • Place of Presentation: 仙台（仙台国際センター）
  • Year and Date: 2017-03-07
• [Presentation] 誘導型多能性幹細胞(iPS細胞）から肺上皮への分化誘導の検討 (2017)
  • Author(s): 桃實徹、新谷康、福井絵里子、神崎隆、川村知裕、舟木壮一郎、南正人、奥村明之進
  • Organizer: 第16回日本再生医療学会総会
  • Place of Presentation: 仙台（仙台国際センター）
  • Year and Date: 2017-03-07
• [Presentation] C-type natriuretic peptide atteuates bleomycin-induced fibrosis and inflammation in murine lung (2015)
  • Author(s): Kimura T,Nojiri T, Hosoda H, Shintani Y, Inoue M, Miyazato M, Okumura M, Kangawa K
  • Organizer: 16th World Conference on Lung Cancer
  • Place of Presentation: Denver,United States of America
  • Year and Date: 2015-09-06
  • Int'l Joint Research
• [Presentation] CNP attenuates renal toxicity induced by cisplatin in murine kidney (2015)
  • Author(s): Kimura T,Nojiri T, Hosoda H, Miyazato M, Kangawa K
  • Organizer: International Conference on cGMP(7)
  • Place of Presentation: Trier,the Federal Republic of Germany
  • Year and Date: 2015-06-19
  • Int'l Joint Research
• [Presentation] Establishment of a new mouse model for postoperative acute exacerbation in interstitial lung diseases (2015)
  • Author(s): Kimura T,Nojiri T, Hosoda H, Shintani Y, Inoue M, Miyazato M, Okumura M, Kangawa K
  • Organizer: European Conference on General Thoracic Surgery(32)
  • Place of Presentation: Lisbon,Portuguese Republic
  • Year and Date: 2015-05-31
  • Int'l Joint Research
• [Presentation] C-type natriuretic peptide atteuates acute and chronic inflammatory reactions in murine lung (2015)
  • Author(s): Kimura T
  • Organizer: Thoracic Surgery Seminar in Kyoto
  • Place of Presentation: 京都
  • Year and Date: 2015-05-16
• [Presentation] プロスタサイクリンアゴニストONO-1301による肺再生治療の可能性 (2015)
  • Author(s): 舟木壮一郎、新谷 康、奥村明之進、ほか
  • Organizer: 第14回日本再生医療学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2015-03-19 – 2015-03-21
• [Presentation] Sustained-release delivery of prostacyclin analogue(ONO-1301) enhances lung regeneration after pnuemonectomy in mice. (2014)
  • Author(s): Funaki S, Shintani Y, Kawamura T, Nakagiri T, Inoue M, Sawabata N, Minami M, Kimura A, Sakai Y, Miyagawa S, Sawa Y, Okumura M
  • Organizer: American thoracic society Interenational conference
  • Place of Presentation: San Diego,United States of America
  • Year and Date: 2014-05-16 – 2014-05-21
• [Book] 先進医療NAVIGATOR 今日の再生医療 (2016)
  • Author(s): 新谷康
  • Total Pages: 4
  • Publisher: 日本医学出版