| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Research Abstract |
We performed a pre-clinical research to establish pluripotent stem cell (ES/iPS cell)-based therapy for terminal heart failure using ischemic cardiomyopathy animal model. First we injected mouse ES cell-derived and FACS-purified cardiomyocytes (CMs) for rat subacute myocardial infarction (MI) model. However, the therapeutic effect was limited because of low efficiency of engraftment. Next we employed cell sheet technology using temperature-responsive culture dishes (UpCell, CellSeed Inc.) to improve the efficiency, and performed ESC-derived cardiac cell sheet transplantation. We showed that transplantation of the cell sheets ameliorates cardiac dysfunction after MI due to attenuated left ventricular remodeling through various paracrine effects, mainly neovascularization. We also indicated that the paracrine effects are mainly mediated by differentiated CMs (Masumoto H, Ikeda T et al, Stem Cells, 2012). Furthermore, we showed that human iPSC-derived cardiac cell sheet transplantation to rat subacute MI model also showed functional improvement through neovascularization (AHA 2012 abstract #11848). We clearly showed that cell sheet transplantation is one of the promising methods to improve therapeutic effects on pluripotent stem cell-based cardiac regeneration. We also showed excellent therapeutic potential of human iPSC-derived cardiac cell sheets. This result helps to realize iPSC-based cardiac regenerative therapy.
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