Elucidation of Maintenance Mechanism of Tissue Regenerative Potential of Bone Marrow Stem Cells by NO-mediated Cell Competition against Particle Radiation Damage
Project/Area Number |
20H03620
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Review Section |
Basic Section 52040:Radiological sciences-related
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Research Institution | University of Fukui |
Principal Investigator |
MATSUMOTO Hideki 福井大学, 学術研究院医学系部門, シニアフェロー (40142377)
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Co-Investigator(Kenkyū-buntansha) |
前田 宗利 公益財団法人若狭湾エネルギー研究センター, 研究開発部, 主任研究員 (20537055)
平山 亮一 国立研究開発法人量子科学技術研究開発機構, 放射線医学総合研究所 重粒子線治療研究部, 主任研究員(定常) (90435701)
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Project Status |
Completed (Fiscal Year 2022)
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Budget Amount *help |
¥16,380,000 (Direct Cost: ¥12,600,000、Indirect Cost: ¥3,780,000)
Fiscal Year 2022: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2020: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
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Keywords | 組織再生能維持機構 / 骨髄幹細胞 / 粒子放射線 / 細胞競合 / 回復動態 / 放射線感受性 / 粒子線障害 / 組織再生能 / 粒子線 / 組織修復 / 一酸化窒素 |
Outline of Research at the Start |
粒子線がん治療における正常組織の粒子線被ばくの安全性を示す生物学的根拠は得られていない。研究代表者らは粒子線に対する細胞応答において一酸化窒素(NO)が重要な役割を果たしていることを明らかにしてきている。 本研究は粒子線がん治療における正常組織での粒子線被ばくの安全性を放射線治療生物学的に実証するために、粒子線照射した正常およびNO合成酵素欠損マウスの骨髄幹細胞動態(生存率・アポトーシス誘発率・損傷細胞の排除動態・特異的遺伝子/タンパク質発現動態など)を解析し、骨髄幹細胞の粒子線障害に対するNOを介した細胞競合による組織再生能維持機構を明らかにする。
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Outline of Final Research Achievements |
The surviving fraction of bone marrow-derived hematopoietic stem cells/pluripotent progenitor cells in normal mice after a single 5 Gy whole-body irradiation with X-rays, protons, or carbon beams was about 0.03-0.1 at 24 hours after irradiation, about 0.1 at 7 days, and recovered to about 0.2-0.7 after 14 days. These results suggest that the DNA damage response mechanism is not induced in damaged bone marrow-derived hematopoietic stem cells/pluripotent progenitor cells and is eliminated, and that bone marrow tissue recovery is induced by new bone marrow-derived hematopoietic stem cells/pluripotent progenitor cells after 7 days of irradiation.
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Academic Significance and Societal Importance of the Research Achievements |
X線と比較して、粒子線により損傷した骨髄由来造血幹細胞/多能性前駆細胞の回復が遅延することが示され、粒子線がん治療における治療計画作成時において、照射野内に含まれる骨髄組織の被ばくを極力避けるようにすべきであることが示唆された。
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Report
(4 results)
Research Products
(60 results)
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[Journal Article] A potential renewed use of very heavy ions for therapy: Neon minibeam radiation therapy.2021
Author(s)
Prezado Y, Hirayama R, Matsufuji N, Inaniwa T, Martinez-Rovira I, Seksek O, Bertho A, Koike S, Labiod D, Pouzoulet F, Polledo L, Warfving N, Liens A, Bergs J, Shimokawa T.
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Journal Title
Cancers (Basel)
Volume: 13
Issue: 6
Pages: 1356-1356
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Lethal DNA lesions caused by direct and indirect actions of X-rays are repaired via different DSB repair pathways under aerobic and anoxic conditions.2021
Author(s)
Hirayama R, Ito A, Uzawa A, Matsumoto Y, Noguchi M, Li H, Suzuki M, Ando K, Okayasu R, Hasegawa S, Furusawa Y.
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Journal Title
Radiat Res
Volume: in press
Issue: 5
Pages: 1-1
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Green one-step synthesis of medical nanoagents for advanced radiation therapy.2020
Author(s)
Salad-Leza D, Porcel E, Yang X, Stefancikova L, Bolsa-Ferruz M, Savina F, Dragoe D, Guerquin-Kern J-L, Wu T, Hirayama R, Remita H, Locombe S.
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Journal Title
Nanotech Sci Appl
Volume: 13
Pages: 61-76
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] Elucidation of immune response in murine models of pancreatic cancer receiving combination therapy of proton beam irradiation and anti-PD-L1 antibody2022
Author(s)
Alessandro Nasti, Yoshio Sakai, Tuyen Thuy Bich Ho, Akihiro Seki, Shingo Inagaki, Norihiko Ogawa, Kyo Kume, Munetoshi Maeda, Hiroyasu Tamamura, Kazutaka Yamamoto, Makoto Sasaki and Shuichi Kaneko
Organizer
第51回日本免疫学会学術集会
Related Report
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[Presentation] Antitumor effect of proton beam irradiation and anti-PD-L1 antibody combination therapy in subcutaneous murine models of pancreatic cancer.2021
Author(s)
Alessandro Nasti, Yoshio Sakai, Norihiko Ogawa, Masaki Miyazawa, Shingo Inagaki, Tuyen Thuy Bich Ho, Hiroki Nomura, Akihiro Seki, Kyo Kume, Munetoshi Maeda, Makoto Sasaki, Shuichi Kaneko
Organizer
The 6th European Congress of Immunology
Related Report
Int'l Joint Research
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