Establishment of safe and efficient cardiac reprogramming methods by controlling intracellular metabolism and histone modification.
| Project/Area Number |
16H04725
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Medical genome science
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| Research Institution | Ritsumeikan University |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥16,380,000 (Direct Cost: ¥12,600,000、Indirect Cost: ¥3,780,000)
Fiscal Year 2019: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2018: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2017: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2016: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
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| Keywords | 再生医学 / 幹細胞生物学 / リプログラミング / 細胞内代謝 / 心筋再生 / 幹細胞 / 代謝 / エピジェネティクス |
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| Outline of Final Research Achievements |
Although induced pluripotent stem (iPS) cell-based cardiac regeneration therapy has been expected, safety, costs, and duration of iPS cell derivation are considered as barriers against the clinical application. To overcome these problems, we modified the reprogramming process and created cardiac myocytes directly from fibroblasts rapidly and efficiently with few risks of tumorigenesis. Cardiac myocytes were induced from four factor-mediated reprogramming fibroblasts, while these cells are not susceptible to iPS cell formation. Global gene expression analysis and metabolome analysis revealed that these reprogramming cells seem to be early mesodermal cells including cardiac progenitors but not iPS progenitor cells. In addition, this cardiac reprogramming is promoted by activation of aerobic metabolism and chromatin-modifying enzymes. The results above may contribute to establishment of the novel strategy for safe and efficient cardiac regeneration therapy.
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| Academic Significance and Societal Importance of the Research Achievements |
心筋細胞の脱落が激しい重篤な末期心不全を治療する方法の一つとして、多能性幹細胞から心筋細胞を分化誘導させ移植する再生療法の実現が期待されている。人工多能性幹細胞は、胚性幹細胞の弱点である倫理的問題や拒絶反応に伴う移植不全を解決できる一方で、移植後の腫瘍形成や株間の分化効率の相違、実用化のための高額な費用など解決すべき問題は多い。本研究では、研究代表者が独自に見出した手法に加え、代謝とクロマチン修飾に関連する制御因子を利用して、安全かつ効率的に心筋細胞を作製する方法を開発した。この研究成果は、安全かつ効率的な心筋再生のための新たなツールとしてその実用化が期待できる。
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Report
(5 results)
Research Products
(33 results)
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[Journal Article] Chimeric G-CSF receptor-mediated STAT3 activation contributes to efficient induction of cardiomyocytes from mouse induced pluripotent stem cells.2019
Author(s)
Tsukamoto T, Sogo T, Ueyama T, Nakao S, Harada Y, Ihara D, Akagi Y, Kida YS, Hasegawa K, Nagamune T, Kawahara M, Kawamura T.
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Journal Title
Biotechnol J
Volume: -
Issue: 2
Pages: 1900052-1900052
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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