| Project/Area Number |
14370417
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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 |
Thoracic surgery
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| Research Institution | Saitama Medical School |
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Principal Investigator |
KYO Syunei Saitama Medical School, Dept CV.Surgery, Professor, 医学部, 教授 (30153232)
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| Co-Investigator(Kenkyū-buntansha) |
MAZDA Osamu Kyoto Prefectural University of Medicine, Dept Microbiology, Associate Professor, 医学部, 助教授 (00271164)
UMEZAWA Akihiro National Research Institute for Child Health and Development, Dept Reproductive Biology and Pathology, Director, 生殖医療部, 部長 (70213486)
GOJO Satoshi Saitama Medical School, Dept CV.Surgery, Associate Professor, 医学部, 講師 (90316745)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥8,400,000 (Direct Cost: ¥8,400,000)
Fiscal Year 2003: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2002: ¥5,000,000 (Direct Cost: ¥5,000,000)
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| Keywords | Stem_Cell / Cardiomyocyte / Regenerative Medicine / Heart Failure / Cell Transplantation |
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| Research Abstract |
The phenomenon of regeneration is of growing interest to medical researchers. One of the object is restoration of function to a failing heart through cell transplantation, and there have been many reports seeking donor sources of stem cells, i.e. : stem cells in marrow or skeletal muscle and ES cells. In particular, reports of mesenchymal stem cell differentiation into nerve cell, myocardial cell, skeletal muscle cell, and vascular endothelial cell series have drawn attention to cell plasticity. However, it is still unclear how the stem cells can differentiate or transdifferentiate into mature cells. Moreover, we cannot maintain the stemness of the cells during cell proliferation.
We examined whether gene transfer could affect both differentiation process and proliferation control. Bone marrow-derived mesenchymal stem cells, which we isolated in previous study, were transduced with Nkx2.5 and GATA4 genes that are involved in the commitment to cardiomyocytes at the initial stage. The efficacy of the in vitro differentiation to cardiomyocytes increased up to 100 fold times, compaired with non-transfectant. But, the in vivo experiment failed to demonstrate the effect of gene transfer by pathological analyses. We are thinking that the rare survival rate after cell grafting into the heart made the quantitative analyses difficult. Next, Telomerase/E6/E7/Bmi-1 were transduced into the human mesenchymal stem cells to increase the prolifelation activity. The transduced human mesenchymal stem cells proliferated over 80 population doublings without interfering with cardiomyogenic differentiation. The cells clearly exhibited differentiated cardiomyocyte phenotypes in vitro as revealed by immunocytochemistry, RT-PCR, and action potential recording. Human mesenchymal stem cells with an extended life span can be used to produce a good experimental model of cardiac cell transplantation and may serve as a highly useful cell source for cardiomyocyte transplantation.
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