2022 Fiscal Year Final Research Report
Selection of bone marrow ALDH bright cells for treatment of pulmonary fibrosis focusing on changes in bone marrow characteristics
| Project/Area Number |
20K08519
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 53030:Respiratory medicine-related
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| Research Institution | Hiroshima University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | Aldehyde dehydrogenase / ALDH / 線維化 / 細胞治療 / 骨髄 / 肺線維症 / 酸化ストレス / 性差 |
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| Outline of Final Research Achievements |
In this research project, we found the following 3 points.
1) Intravenous administration of bone marrow-derived ALDH-high expressing cells (ALDHbr) improves murine pulmonary fibrosis, 2) female-derived ALDHbr are more resistant to oxidative stress than males and have a higher therapeutic effect, and 3) antioxidant stress is an important mechanism by which bone marrow-derived ALDHbr improves fibrosis.
Since improvement was confirmed by administration during the fibrotic phase, ALDHbr is a promising cell therapy tool for clinical application to human pulmonary fibrosis that has already developed. On the other hand, gender differences in efficacy were evident. The fact that past clinical trials using ALDHbr did not show the expected effect from mouse experiments might be due to differences in efficacy by sex.
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| Free Research Field |
呼吸器内科
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| Academic Significance and Societal Importance of the Research Achievements |
本研究においてLin―/ALDHbr治療により、ブレオマイシンの投与で発生する活性酸素種 (ROS)が抑制され線維化が抑制されるメカニズムを明らかとした。今日までいまだ有効な治療法のない肺線維症は、女性より男性に多く認められる。本研究によって得られた性差は、これらヒト臨床における性差と関連がある可能性がある。また、過去のALDHbrを用いた臨床試験においてマウス実験から期待されたほどの効果が認められなかったのは性差による効果の違いが関与している可能性があり、ドナーおよびレシピエントの性別に注意を払うことで過去に有効性を示すことができなかったALDHbr治療を再度見直す必要がある。
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