Development of new therapy using mesenchymal stem cells for exacerbation of COPD

• Project/Area Number: 17K16062
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Respiratory organ internal medicine
• Research Institution: Keio University
• Principal Investigator: Asami Takahiro 慶應義塾大学, 医学部(信濃町), 共同研究員 (50623865)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 間葉系幹細胞 / 肺炎球菌 / COPD増悪 / 肺炎球菌感染症 / 慢性閉塞性肺疾患 / 感染症 / 免疫学 / 内科

Outline of Final Research Achievements

Chronic obstructive pulmonary disease (COPD) can be exacerbated by bacterial or viral infections. COPD exacerbation is considered to be the main cause of death from COPD, but the detailed mechanism of the disease state is unknown. The cause of COPD exacerbation is pneumococcal infection. At present, antibiotics, steroids, and bronchodilators are used, but they are not sufficient, and new treatment is required.
First, we created a pneumococcal infection model mouse, and obtained the result which indicated the control of the inflammation of the pneumonia by the mesenchymal stem cell (MSC) administration. MSC administration effect will be examined for the pneumococcus pulmonary emphysema model in future.

Academic Significance and Societal Importance of the Research Achievements

感染症および感染により悪化する病態は、これまで抗菌薬治療が主に用いられたきた。しかし抗菌薬治療だけでは十分な効果が得られない場合があり、この原因には宿主（ヒト）の要因として、自らの免疫応答が強くなりすぎたり、不十分であることが考えられる。本研究では肺炎球菌感染の過剰な炎症をMSCの投与により抑制できたことを示唆している。抗菌薬治療で軽快が困難だった病態が、間葉系幹細胞の投与により予後が改善する可能性がある。

Research Products

• [Journal Article] 抗酸菌の検査法 薬剤感受性検査 (2019)
  • Author(s): 浅見貴弘、御手洗聡
  • Journal Title: Medical Technology Volume: 47 Pages: 126-131
• [Journal Article] Clinico-microbiological analysis of 121 patients with pulmonary Mycobacteroides abscessus complex disease in Japan ? An NTM-JRC study with RIT (2018)
  • Author(s): Morimoto Kozo、Nakagawa Taku、Asami Takahiro、Izumi Kiyohiko、Hayashi Yuta、Matsuda Shuichi、Murase Yoshiro、Yano Ryozo、Takasaki Jin、Betsuyaku Tomoko、Aono Akio、Goto Hajime、Hoshino Yoshihiko、Kurashima Atsuyuki、Ato Manabu、Ogawa Kenji、Hasegawa Naoki、Mitarai Satoshi
  • Journal Title: Respiratory Medicine Volume: 145 Pages: 14-20
  • DOI: 10.1016/j.rmed.2018.10.012
  • Peer Reviewed / Open Access
• [Journal Article] Association between six-minute walk test parameters and the health-related quality of life in patients with pulmonary Mycobacterium avium complex disease. (2018)
  • Author(s): Yagi K, Asakura T, Namkoong H, Suzuki S, Asami T, Okamori S, Kusumoto T, Funatsu Y, Kamata H, Nishimura T, Ishii M, Betsuyaku T, Hasegawa N.
  • Journal Title: BMC Pulm Med. Volume: 18(1) Issue: 1 Pages: 114-121
  • DOI: 10.1186/s12890-018-0686-5
  • Peer Reviewed / Open Access
• [Journal Article] Clarithromycin expands CD11b+Gr-1+ cells via the STAT3/Bv8 axis to ameliorate lethal endotoxic shock and post-influenza bacterial pneumonia. (2018)
  • Author(s): Namkoong H1,2, Ishii M1, Fujii H3, Yagi K1, Asami T1, Asakura T1, Suzuki S1, Hegab AE1, Kamata H1, Tasaka S1, Atarashi K4, Nakamoto N5, Iwata S6,7, Honda K4, Kanai T5, Hasegawa N6, Koyasu S4,8, Betsuyaku T1.
  • Journal Title: PLOS Pathogens Volume: 14(4) Issue: 4 Pages: e1006955-e1006955
  • DOI: 10.1371/journal.ppat.1006955
  • Peer Reviewed / Open Access
• [Journal Article] Anti-inflammatory roles of mesenchymal stromal cells during acute Streptococcus pneumoniae pulmonary infection in mice (2018)
  • Author(s): Asami Takahiro、Ishii Makoto、Namkoong Ho、Yagi Kazuma、Tasaka Sadatomo、Asakura Takanori、Suzuki Shoji、Kamo Tetsuro、Okamori Satoshi、Kamata Hirofumi、Zhang Haiyue、Hegab Ahmed E.、Hasegawa Naoki、Betsuyaku Tomoko
  • Journal Title: Cytotherapy Volume: 20 Issue: 3 Pages: 302-313
  • DOI: 10.1016/j.jcyt.2018.01.003
  • Peer Reviewed / Open Access