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リエゾンラボ研究会
発表内容

Title:
Multiple Approaches for Cardiac Regeneration with Pluripotent Stem Cells, Small Molecules, and Tissue Engineering

Jun K Yamashita
1Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan
2Department of Stem Cell Differentiation, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan

Abstract:
 We have been investigating cardiovascular cell differentiation and regeneration with the use of pluripotent stem cells, that is, embryonic stem (ES) and induced pluripotent stem (iPS) cells. Previously, we established a systematic cardiovascular cell differentiation system using Flk1+ cells as common progenitors. We previously found that an immunosuppressant, cyclosporin-A, showed a novel effect specifically acting on Flk1+ mesoderm cells to drastically increase cardiac progenitors and cardiomyocytes. We applied these results to set up a small molecule screening system for cardiomyocyte differentiation, and found a potent compound enhancing cardiomyocyte differentiation at nanomolar level. Currently, we are examining the potential of the compound as a cardiac regenerative drug with systemic administration to rat myocardial infarction model.
 We are also examining cell therapy strategies combining the cell sheets technology (collaboration with Tokyo Women’s Medical University) and stem cell biology. We observed that transplantation of cardiac tissue sheet re-assembled with defined cardiovascular populations to rat myocardial infarction model significantly improved systolic function through paracrine effects including neovascularization but not with direct cellular contribution. To improve cellular contribution after transplantation, we recently developed a novel tissue engineering method in which large viable cardiac cell mass (more than 1mm thickness) can be formed by piling up the cell sheets (up to 15 sheets). Moreover, we succeeded in identifying and purifying a novel human cardiomyocyte-committed progenitor population during human iPS cell differentiation that showed highly selective and efficient differentiation exclusively to cardiomyocytes after transplantation. We are, thus, trying to explore novel cardiac regenerative strategies through integrative combinations of stem cell and chemical biology together with tissue engineering.