Project/Area Number |
10470170
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Circulatory organs internal medicine
|
Research Institution | Keio University |
Principal Investigator |
OGAWA Satoshi KEIO UNIVERSITY, DEPT. OF MEDICINE, PROFESSOR, 医学部, 教授 (90124940)
|
Co-Investigator(Kenkyū-buntansha) |
SANO Motoaki KEIO UNIVERSITY, DEPT. OF MEDICINE, INSTRUCTOR, 医学部, 助手 (30265798)
KODAMA Hiroaki KEIO UNIVERSITY, DEPT. OF MEDICINE, INSTRUCTOR, 医学部, 助手 (70225457)
FUKUDA Keiichi KEIO UNIVERSITY, DEPT. OF MEDICINE, ASSISTANT PROFESSOR, 医学部, 講師 (20199227)
KATO Takahiro KEIO UNIVERSITY, DEPT. OF MEDICINE, INSTRUCTOR, 医学部, 助手 (60276219)
TAKAHASHI Toshiyuki KEIO UNIVERSITY, DEPT. OF MEDICINE, INSTRUCTOR, 医学部, 助手 (20265804)
|
Project Period (FY) |
1998 – 1999
|
Project Status |
Completed (Fiscal Year 1999)
|
Budget Amount *help |
¥13,000,000 (Direct Cost: ¥13,000,000)
Fiscal Year 1999: ¥4,800,000 (Direct Cost: ¥4,800,000)
Fiscal Year 1998: ¥8,200,000 (Direct Cost: ¥8,200,000)
|
Keywords | Bone marrow stromal cell / Cardiomyocyte / Stem cell / Regenerative medicine / Differentiation / cardiomyocyte / differentiation / mnarrow stroma / development |
Research Abstract |
We have isolated a cardiomyogenic cell line from murine bone marrow stromal cells. The cells showed a fibroblast-like morphology, but the morphology changed after 5-azacytidine treatment in approximately 30% of the cells; they connected with adjoining cells after 1 week, formed myotube-like structures and began spontaneous beating after 2 weeks, and beat synchronously after 3 weeks. The expressed ANP and BNP. Electron microscopy revealed a cardiomyocyte-like ultrastructure including typical sarcomeres and atrial granules. These cells had several types of action potentials; sinus node-like and ventricular cell-like action potentials. All cells had a long action potential duration or plateau, a relatively shallow resting membrane potential, and a pacemaker-like late diastolic slow depolarization. Analysis of the isoform of contractile protein genes, such as myosin heavy chain, myosin light chain and α-actin, indicated that their muscle Nkx2.5/Csx, GATA4, TEF-1 and MEF-2C mRNA before 5-azacytidine treatment, and expressed MEF-2A and MEF-2D after treatment. The use of adult tissues as a source of cardiomyocytes makes this system particularly appropriate for the development of gene therapy strategies for heart disease. This new cell line provides a powerful model for the study of cardiomyocytes differentiation.
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