2005 Fiscal Year Final Research Report Summary
Development of the way how to induce efficient cardiomyocyte differentiation using stem cells and attempt for cell transplantation therapy against heart failure
| Project/Area Number |
15390242
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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 |
Circulatory organs internal medicine
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| Research Institution | The University of Tokyo |
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Principal Investigator |
YAMAZAKI Tsutomu The University of Tokyo, Faculty of Medicine, Professor, 医学部附属病院, 特任教授 (60251245)
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| Co-Investigator(Kenkyū-buntansha) |
HAYASHI Doubun The University of Tokyo, Faculty of Medicine, Visiting Assistant Professor, 医学部附属病院, 客員助教授 (80313104)
NAGAI Ryozo The University of Tokyo, Faculty of Medicine, Professor, 医学部附属病院, 教授 (60207975)
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| Project Period (FY) |
2003 – 2005
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| Keywords | HMGA / P19CL6 / cardiomyocyte differentiation / cardiac development / Xenopus embryo / molecular biology / organ preservation / supercooling technology |
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| Research Abstract |
1) Members of the high-mobility-group proteins A (HMGA) family are transcription factors expressed ubiquitously in fetus. They regulate expression of numerous genes by participating in specific protein-DNA and protein-protein interactions that induce both structural changes in chromatin substrates and the formation of transcriptional complexes on the promoter/enhancer region of their target genes. We demonstrated that HMGA2, a member of the HMGA family, plays a critical role in cardiomyocyte differentiation and cardiac development. Stable overexpression of HMGA2 strongly enhanced the differentiation of the P19CL6 cardiomyogenic cell line into beating cardiomyocytes while its inhibition blocked it. We also found that the Smad transcription factors and HMGA2 formed complex, bound to an evolutionarily conserved sequence on the Csx/Nkx2.5 promoter and displayed synergistic transcriptional activation. Furthermore, inhibition of HMGA2 in Xenopus embryos blocked cardiomyocyte differentiation
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and normal heart formation, implying an essential role for HMGA2 in cardiac development also in vivo.
2) Current medical transplantation confronts major problems such as the shortage of donors and geographical restrictions that inhibit efficient utilization of finite donor organs within their storage lives. To overcome these issues, expanding organ preservation time has become a major concern. We investigated whether a strategy which best preserves organ grafts can be achieved by the use of a newly-developed refrigerating chamber, which is capable of establishing a supercooled and unfrozen state stably by generating an electrostatic field in its inside. When adult rat organs such as heart, liver, and kidneys were stored in the supercooled conditions, the levels of major biochemical markers leaked from the preserved organs were significantly lower than in the ordinary hypothermic storage. No apparent tissue damages were observed histologically after the supercooled preservation. Our results suggest that the use of this supercooling refrigerator improves organ preservation and may provide an innovative technique for human organ transplantation. Less
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[Journal Article] Genetic analysis in a patient with recurrent cardiac myxoma and endocrinopathy.2005
Author(s)
Imai Y, Taketani T, Maemura K, Takeda N, Harada T, Nojiri T, Kawanami D, Monzen K, Hayashi D, Murakawa Y, Ohno M, Hirata Y, Yamazaki T, Takamoto S, Nagai R.
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Journal Title
Circulation Journal 69(8)
Pages: 994-995
Description
「研究成果報告書概要(欧文)」より
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