Repairing of radiation-induced tissue damage by extracellular vesicles that mediate interaction of tissue-specific stem cells
Project/Area Number |
17H04264
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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 |
Research Field |
Radiation science
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Research Institution | Hiroshima University |
Principal Investigator |
ICHINOHE TATSUO 広島大学, 原爆放射線医科学研究所, 教授 (80314219)
|
Co-Investigator(Kenkyū-buntansha) |
高山 英次 朝日大学, 歯学部, 准教授 (70533446)
三浦 康生 藤田医科大学, 医学部, 教授 (70605146)
前川 平 京都大学, 医学研究科, 教授 (80229286)
|
Project Period (FY) |
2017-04-01 – 2020-03-31
|
Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
Fiscal Year 2019: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
|
Keywords | 被ばく医療 / 組織再生治療 / 間葉系幹細胞 / 細胞外小胞 / 間葉系細胞 |
Outline of Final Research Achievements |
In this study, we aimed at establishing the scientific foundation of novel cellular treatment of radiation-induced organ damage as well as acute radiation syndrome by use of mesenchymal stromal/stem cells (MSCs) and MSC-derived extracellular vesicles (EVs). Using appropriate mouse hematopoietic cell transplantation models conditioned with total-body irradiation (TBI), we have revealed that systemic infusion of human bone marrow-MSC-derived nanovesicles prolonged the survival of mice with acute graft-versus-host disease (GVHD) and reduced the pathologic damage in multiple GVHD/TBI-targeted organs, particularly that of the gastrointestinal system. This effect was not reproducible when we used fibroblast-derived EVs, suggesting the special characteristics of MSC-derived EVs. Also by using microarrays of microRNA, we found that predominant presence of miR-125a-3p in BM-MSC-derived EVs as compared with fibroblast-derived EVs.
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Academic Significance and Societal Importance of the Research Achievements |
チェルノブイリ原子力発電所事故、東海村JCO臨界事故、福島第一原子力発電所事故等、現代社会は急性放射線障害が発生するリスクとの共存を求められている。また、放射線は、各種のX線検査、悪性腫瘍の治療など日常的な医療に汎用されているが、一部の患者に起こり得る医療用放射線使用に関連する組織障害への根本的な治療法は開発されていない。したがって、本研究の成果により、骨髄や脂肪組織に由来する間葉系幹細胞を放射線障害の細胞治療医薬品として開発する道筋が得られたことの意義は非常に大きい。
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Report
(4 results)
Research Products
(21 results)
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[Journal Article] Prognostic impact of melphalan dose and total body irradiation use in patients with acute myeloid leukemia undergoing allogeneic stem cell transplantation with reduced-intensity conditioning.2019
Author(s)
Harada K, Yanada M, Machida S, Kanamori H, Onizuka M, Ozawa Y, Kobayashi H, Sawa M, Katayama Y, Ohashi K, Kanda J, Ichinohe T, Atsuta Y, Yano S.
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Journal Title
Leuk Lymphoma.
Volume: 60
Issue: 6
Pages: 1493-1502
DOI
Related Report
Peer Reviewed
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[Journal Article] Suppression effect of adipose tissue-derived mesenchymal stem cells isolated from β2-microglobulin-deficient mice.2018
Author(s)
Masuda J, Takayama E, Ichinohe T, Strober W, Mizuno-Kamiya M, Ikawa T, Kitani A, Kawaki H, Fuss IJ, Kawamoto H, Seno A, Vaidyanath A, UmemuraN, Mizutani A, Kasai T, Honjo Y, Satoh A, Murakami H, Katsura Y, Kondoh N, Seno M
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Journal Title
Exp Ther Med
Volume: 16
Pages: 4277-4282
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Bortezomib interferes with adhesion of B cell precursor acute lymphoblastic leukemia cells through SPARC up-regulation in human bone marrow mesenchymal stromal/stem cells.2017
Author(s)
Iwasa M, Miura Y, Fujishiro A, Fujii S, Sugino N, Yoshioka S, Yokota A, Hishita T, Hirai H, Andoh A, Ichinohe T, Maekawa T.
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Journal Title
Int J Hematol.
Volume: 105
Issue: 5
Pages: 587-597
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Isolation of mesenchymal stromal/stem cells from cryopreserved umbilical cord blood cells2017
Author(s)
Fujii S, Miura Y, Iwasa M, Yoshioka S, Fujishiro A, Sugino N, Kaneko H, Nakagawa Y, Hirai H, Takaori-Kondo A, Ichinohe T, Maekawa T.
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Journal Title
Journal of Clinical and Experimental Hematopathology
Volume: 57
Issue: 1
Pages: 1-8
DOI
NAID
ISSN
1346-4280, 1880-9952
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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