| Project/Area Number |
18K16405
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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 | Nihon University |
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Principal Investigator |
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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 |
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 脱分化脂肪細胞 / iPS由来心筋細胞 / 脂肪組織由来幹細胞 / ES細胞由来心筋 / 成熟化 / iPS細胞 / 心筋分化 |
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| Outline of Final Research Achievements |
We created an indirect co-culture system of human-derived dedifferentiated adipocytes and human-derived iPS-derived cardiomyocytes to examine the effects of adipose lineage-committed undifferentiated cells on cardiomyocytes by soluble factors. As a result, the interaction between the two cells was predominantly an inflammatory response, with cardiomyocytes having a lower heart rate and less sensitivity to catecholamine, which accelerates heart rate. In addition, approximately 30% of cardiomyocytes underwent apoptosis, purportedly programmed cell death, and mitochondrial function analysis showed reduced oxidative stress tolerance and lower oxygen consumption. These results indicate that adipose lineage-committed undifferentiated cells may reduce cardiomyocyte function through secretion of proinflammatory cytokines.
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| Academic Significance and Societal Importance of the Research Achievements |
脂肪組織が心不全の病態に寄与していることが近年明らかになっている。このような病態下の脂肪組織では成熟脂肪細胞は膨化し、脂肪リネージにコミットした未熟な細胞集団はその分化が障害される”リモデリング”という変化が起こる。このうち脂肪リネージにコミットした未熟な細胞集団がどのように心不全の病態形成に寄与するかは明らかになっていない。我々の結果は、心不全において脂肪組織が関わる病態の解明やiPS心筋移植において移植心筋の機能や生存率を最大化させる治療戦略の基盤となり得ると考えられる。
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