Project/Area Number |
12307016
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Research Category |
Grant-in-Aid for Scientific Research (A)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Circulatory organs internal medicine
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Research Institution | Keio University |
Principal Investigator |
OGAWA Satoshi KEIO UNIVERSITY SCHOOL OF MEDICINE, DEPARTMENT OF INTERNAL MEDICINE PROFESSOR, 医学部, 教授 (90124940)
|
Co-Investigator(Kenkyū-buntansha) |
KATOH Takahiro KEIO UNIVERSITY, LECTURER (2000) medicine assist, 医学部, 助手 (60276219)
TAKAHASHI Eiichi KEIO UNIVERSITY, LECTURER (2000-2001) medicine assist, 医学部, 助手 (00276247)
FUKUDA Keiichi KEIO UNIVERSITY, ASSISTANT PROFESSOR medicine, 医学部, 講師 (20199227)
TOMITA Yuichi KEIO UNIVERSITY, LECTURER medicine assistant, 医学部, 助手 (00296568)
HAKUNO Daihiko KEIO UNIVERSITY, LECTURER (2000-2001) medicine assist, 医学部, 助手 (80286476)
|
Project Period (FY) |
2000 – 2002
|
Project Status |
Completed (Fiscal Year 2002)
|
Budget Amount *help |
¥43,500,000 (Direct Cost: ¥37,200,000、Indirect Cost: ¥6,300,000)
Fiscal Year 2002: ¥13,650,000 (Direct Cost: ¥10,500,000、Indirect Cost: ¥3,150,000)
Fiscal Year 2001: ¥13,650,000 (Direct Cost: ¥10,500,000、Indirect Cost: ¥3,150,000)
Fiscal Year 2000: ¥16,200,000 (Direct Cost: ¥16,200,000)
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Keywords | STEM CELL / REGENERATION / BONE MARROW / CARDIOMYOCYTE / TRANSDIFFERENTIATION / HEART FAILURE / TRANSPLANTATION / 再生医学 / 骨髄細胞 / 発生 |
Research Abstract |
WE HAVE ISOLATED A CARDIOMYOGENIC CELL LINE (CMG CELL) FROM MURINE BONE MARROW MESENCHYMAL STEM CELLS. THE CELLS SHOWED A FIBROBLAST-LIKE MORPHOLOGY, BUT THE MORPHOLOGY CHANGED AFTER 5-AZACYTIDINE EXPOSURE. THEY BEGAN SPONTANEOUS BEATING AFTER 2 WEEKS, AND EXPRESSED ANP AND BNP. ELECTRON MICROSCOPY REVEALED A CARDIOMYOCYTE-LIKE ULTRASTRUCTURE. THESE CELLS HAD SEVERAL TYPES OF ACTION POTENTIALS; SINUS NODE-LIKE AND VENTRICULAR CELL-LIKE ACTION POTENTIALS. THE ISOFORM OF CONTRACTILE PROTEIN GENES INDICATED THAT THEIR MUSCLE PHENOTYPE WAS SIMILAR TO FETAL VENTRICULAR CARDIOMYOCYTES. THEY MUSCLE PHENOTYPE WAS SIMILAR TO FETAL VENTRICULAR CARDIOMYOCYTES. THEY EXPRESSED □_<1A>, □_<1B>, □_<1D>, AND □_2 ADRENERGIC AND M1 AND M2 MUSCARINIC RECEPTORS. STIMULATION WITH PHENYLEPHRINE, ISOPROTERENOL AND CARBACHOL INCREASED ERK PHOSPHORYLATION AND SECOND MESSENGERS. ISOPROTERENOL INCREASED THE BEATING RATE, WHICH WAS BLOCKED WITH CGP20712A (□_1-SELECTIVE BLOCKER). THESE FINDINGS INDICATED THAT CELL TRANSPLANTATION THERAPY FOR THE PATIENTS WITH HEART FAILURE MIGHT POSSIBLY BE ACHIEVED USING THE REGENERATED CARDIOMYOCYTES FROM AUTOLOGOUS BONE MARROW CELLS IN THE NEAR FUTURE.
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