2012 Fiscal Year Final Research Report
Treatment for heart failure with combination of stem cell sheet technology and sustained release of growth factors
| Project/Area Number |
22591540
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | Kyoto University |
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Principal Investigator |
IKEDA Tadashi 京都大学, 医学系研, 准教授 (40281092)
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| Project Period (FY) |
2010 – 2012
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| Keywords | 細胞シート学 / 幹細胞 / 細胞増殖因子 / ドラッグデリバリーシステム(DDS) / 心不全治療 |
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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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[Journal Article] Pluripotent stem cell-engineered cell sheets re-assembled with defined cardiovascular populations ameliorate reduction in infarct heart function through cardiomyocyte-mediated neovascularization2012
Author(s)
Masumoto H, Matsuo T, Yamamizu K, Uosaki H, Narazaki G, Katayama S, Marui A, Shimizu T, Ikeda T, Okano T, Sakata R, Yamashita JK
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Journal Title
Stem Cells
Volume: 30(6)
Pages: 1196-205
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[Journal Article] Induction and enhancement of cardiac cell differentiation from mouse and human induced pluripotent stem cells with cyclosporin-A2011
Author(s)
Fujiwara M, Yan P, Otsuji TG, Narazaki G, Uosaki H, Fukushima H, Kuwahara K, Harada M, Matsuda H, Matsuoka S, Okita K, Takahashi K, Nakagawa M, Ikeda T, Sakata R, Mummery CL, Nakatsuji N, Yamanaka S, Nakao K, Yamashita JK
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Journal Title
PLoS One
Volume: 6(2)
Pages: e16734
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