| Project/Area Number |
18K16395
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 55030:Cardiovascular surgery-related
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| Research Institution | Yamaguchi University |
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Principal Investigator |
NAKAMURA Tamami 山口大学, 医学部附属病院, 診療助教(4日/週) (40815669)
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 間葉系幹細胞 (MSCs) / 心筋幹細胞 (CDCs) / エクソソーム / 低酸素プレコンディショニング / 陳旧性心筋梗塞モデル / MSCs / 虚血性心疾患 / 他家移植 / 間葉系幹細胞 / 細胞シート |
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| Outline of Final Research Achievements |
While the occurrence of heart failure is increased, the therapeutic chance of cardiac transplantation is seriously limited in Japan. Autogenic or allogenic stem cell transplantation has been intensively investigated, however, recent evidences suggest that the functional differentiation of stem cell is hardly observed in vivo, and that the exosomes secreted from the transplant stimulate the endogenous regeneration, thereby promoting the functional recovery.
We first aimed to study about the allogenic MSCs transplantation, however, given the reason above, we have modified our project and analyzed the MSCs regarding the exosome secretion in comparison with CDCs. CDCs showed the superior function in exosomes secretion or hypoxia-induced activation compared to MSCs. Administration of exosomes from CDCs to chronic myocardial infarction model improved the functionality. We thus suggest that exosomes from CDCs are the novel therapeutic tool against heart failure.
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| Academic Significance and Societal Importance of the Research Achievements |
超高齢社会である我が国において、移植適応年齢を外れる高齢者の心不全は多く、心臓移植に代わる新規治療法の開発が望まれている。幹細胞移植療法が期待されたが、近年、幹細胞が機能的な細胞に分化することは稀で、分泌された成長因子等が内因性の再生を促し、臓器機能を回復させることが判明した。
本研究は「MSCsが分泌するエクソソーム」等に関する検討を行った。幹細胞由来のエクソソームは成長因子等を含み、保存や反復投与が可能で、次世代の治療方法として期待される。検討した結果、CDCsはMSCより優位だった。CDCs由来エクソソームの投与は陳旧性心筋梗塞モデルの心機能を改善させ、新規治療法に成る可能性を示した。
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