Mesenchymal stem cell therapy for pulmonary fibrosis in new mouse model of pulmonary fibrosis

Research Project

Project/Area Number	16K19463
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Respiratory organ internal medicine
Research Institution	Nara Medical University
Principal Investigator	Kumamoto Makiko 奈良県立医科大学, 医学部, 助教 (10623522)
Project Period (FY)	2016-04-01 – 2019-03-31
Project Status	Completed (Fiscal Year 2018)
Budget Amount *help	¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000) Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000) Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords	肺線維症 / 脂肪由来間葉系幹細胞 / 新規肺線維症マウスモデル / 特発性肺線維症 / 線維芽細胞 / 細胞治療
Outline of Final Research Achievements	Adipose-derived mesenchymal stem cells(ASC) ameliorate bleomycin-induced pulmonary fibrosis in mice.In addition, ASCs were also effective in new pulomnary fibrosis model in mice. In this new model, pulmonary fibrosis was initiated by the intravenous introduction of primary human fibroblast lines into immunodeficient mice. The decrease of the expression of fibrotic markers in fibroblasts derived from IPF patient's lung was detected by co-culture with ASC. Hepatocyte growth factor(HGF) produced from ASC is important for this effect.
Academic Significance and Societal Importance of the Research Achievements	特発性肺線維症（IPF）には未だ有効な治療手段がなく、新規治療法の開発は急務である。筆者らはブレオマイシン（BLM）肺線維症モデルにおいて骨髄由来間葉系幹細胞の有効性はすでに報告しているが、今回、骨髄由来に比べて低侵襲で確保が容易な脂肪由来間葉系幹細胞（ASC）の線維化抑制効果について証明した。また、IPF患者由来の線維芽細胞を移入することで作成される、よりIPFの病態に近い新規肺線維症マウスモデルにおいても、ASCの効果を証明した。これらの結果は、IPFに対する間葉系幹細胞の臨床応用に向けて、さらに前進させたと考える。