Abstract 2965: Cardiomyocyte Sheets Derived From Induced Pluripotent Stem (iPS) Cells Improve Cardiac Function and Attenuate Cardiac Remodeling in Myocardial Infarction in Mice
Cell transplantation derived from autologous cells after myocardial infarction is a promising strategy. ES cells represent an attractive candidate cell source for obtaining cardiomyocytes and other useful mesenchymal cell types for such transplantation. However, some controversial problems on their clinical use remain to be elucidated. Induced pluripotent stem (iPS) cells are a potential source of patient-specific pluripotent stem cells that would prevent immune rejection. In this study, we prepared sheet-shaped cardiomyocyte grafts from mouse iPS cells and measured cardiac performance by cardiomyocyte sheets implantation in mouse myocardial infarction model. Mouse iPS cells were maintained on feeder cells and differentiated to cardiac lineage by adding glycogen synthase kinase-3 inhibitor, BIO. Then, a cardiomyocyte derived from mouse iPS cells was cultured in media without glucose. The efficiency of cardiac differentiation was determined by RT-PCR, Quantitative real-time PCR and immunostaining methods. Cardiomyocyte sheets derived from mouse iPS cells were constructed with temperature-responsive, polymer-grafted cell-culture dishes and transplanted to infracted area of mouse myocardial infarction model. Immunostaining analyses revealed that α-actinin+ or Nkx2.5+ cardiomyocyte population was isolated with over 99% purity under non-glucose conditions. RT-PCR analysis also suggested that mouse iPS cells could differentiate to all kind of cardiomyocyte. The cardiomyocyte sheets derived from mouse iPS cells were created and transplanted to mouse myocardial infarction model. In transplantation group, teratoma formations were observed in 50% of animals. However, the fraction shortening was ameliorated and left ventricular end-diastolic dimension was contracted in non-teratoma group by echocardiography analysis. We successfully derived cardiomyocyte sheets from mouse iPS cells by adding BIO and medium change, and then their transplantation on the heart of mouse myocardial infarction model resulted in improving their heart functions. Cardiomyocyte sheet derived from iPS cells are a viable option as an autologous cell source for cardiac repair and a powerful tool for cardiovascular research.