The therapeutic efficacy of mouse ES cell derived cardiac progenitor cell transplantation in the ischemic heart
Grant-in-Aid for Scientific Research (B)
|Allocation Type||Single-year Grants |
|Research Institution||Kyoto University |
KOMEDA Masashi Kyoto University, Graduate School of Medicine, Professor, 医学研究科, 教授 (20303810)
IKEDA Tadashi Kyoto University, Graduate School of Medicine, Associate Professor, 医学研究科, 助教授 (40281092)
NAKAHATA Tatutoshi Kyoto University, Graduate School of Medicine, Professor, 医学研究科, 教授 (20110744)
MATSUBARA Hiroaki Kyoto Prefectural University of Medicine, Professor, 医学研究科, 教授 (10239072)
|Project Period (FY)
2004 – 2006
Completed (Fiscal Year 2006)
|Budget Amount *help
¥12,800,000 (Direct Cost: ¥12,800,000)
Fiscal Year 2006: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2004: ¥5,200,000 (Direct Cost: ¥5,200,000)
|Keywords||ES cell / cell transplantation / old myocardial infarction / myocardial regeneration / Flk1 / 慢性心筋梗塞 / FACS / 急性心筋梗塞 / 陳旧性心筋梗塞|
This study was to investigate and establish the procedure to proliferate and differentiate the mouse Flk1 positive ES cells to cardiac progenitor cells and cardiomyocytes. Then, cell transplantation was done to investigate the proliferation and differentiation of mouse Flk1 positive ES cells after implanted into ischemic myocardium and to check the improvement of cardiac function.
To investigate and establish the procedure to proliferate and differentiate the mouse Flk1 positive ES cells to cardiac progenitor cells and cardiomyocytes.
1) We established the procedure to differentiate and proliferate 3million cardiomyocytes from mouse Flk1 positive ES cells at single approach.
2) We established the procedure to differentiate and proliferate the 2million cardiac progenitor cells (FCV : Flk1 positive, CXCR4 positive, VE-Cadherin negative) from mouse ES cells, with the purity of 80% at single approach.
Cell transplantation study using these mouse ES cell derived cardiac cell line.
1) Flk1 positi
ve cardiac stem/progenitor cells derived from embryonic stem cells improve cardiac function in a dilated cardiomyopathy mouse model.
2) In the mouse acute myocardial infarction model, we transplanted Flk1 positive cardiomyocytes which derived from mouse ES cells. We identified the donor cells survivality, differentiation into cardiomyocytes, restrain the left ventricle dilatation after infarction, and increase the fractional shortening in this model.
3) We performed the old myocardial infarction model using immunodeficiency mouse. We tried the cell transplantation therapy, but it was too difficult to do the therapy, due to the excessive thinness of the infarcted muscle wall.
4) We performed the old myocardial infarction model using immunodeficiency rat. 4 weeks after the induction of myocardial infarction, we transplanted 1million cardiac progenitor cells from mouse Flk1 positive ES cell.
First, we examined the transplanted cells survival and differentiation.
2 weeks after cell transplantation, recipient rats were sacrificed and specimens were made. We confirmed a large mass of transplanted cells survivajity by GFP staining and the differentiation to cardiomyocytes.
We evaluated the effect of cell transplantation by checking the cardiac function such as echocardiography and cardiac catheterization. But, there was no apparent effect of improvement of cardiac function.
Now we increasing the number of this model, and rechecking the improvement of cardiac function Less
Report (4 results)
Research Products (4 results)