Abstract 11156: Very High Engraftment, Proliferation, and Therapeutic Potential of IPSC-Derived Cardiomycytes
Human induced pluripotent stem cells-derived cardiomyocytes (iPSC-CMs) are one of the promising sources for cardiac cell therapy. Although several investigators reported the positive effect of the iPSC-CMs based cell therapy, the treatment efficiency was limited. One of the major reasons of limited efficiency should be a poor engraftment of injected cells. In addition, there have not been enough data about what kind of cells are the optimal cells for cardiac cell therapy. Therefore, the optimization of injected cells can be important. Now we compared the engraftment efficiency of intramyocardially injected iPSC-CMs by the differentiation stages. Using cell lines continuously expressing luciferase, we traced the engraftment ratio(ER) of the injected purified iPSC-CMs over time by in vivo imaging system (IVIS). When we compared the ER of undifferentiatied iPSCs, day4 mesodermal cells, day8, day20, and day30 iPSC-CMs after the initial differentiation, the ER was significantly higher in day20-CMs (iPSCs; 0%, day4; 0%, day8-CMs; 41.2%, day20-CMs; 167.6%, day30-CMs; 71.2% at 2 month after the initial injection). To demonstrate their therapeutic potential, day20-CMs were transplanted into NOG mice with myocardial infarction. Compared to control, mice transplanted with day20-CMs showed significant functional improvement measured by echocardiography (fractional shortening at 3 months: 25.4±5.4% vs 17.9±4.3% respectively; p<0.001). Moreover, IVIS signal was gradually increased during the follow-up 3 months and the signal at the time of 3 months was 7 fold higher than the initial signal just after injection, suggesting that engrafted CMs could proliferate in the host heart. Actually, the ratio of Ki67(+) CMs among engrafted CMs were significantly higher than that of in vitro cultured CMs at each time point (1 month; 17.7% vs. 4.0%, 2 months; 7.5% vs. 1.9%, 3 months; 4.7% vs. 0.7%; p<0.05 at each time point). These results suggested that day20-CMs had very high engraftment, proliferation, and therapeutic potential, leading to the clinical application of iPSC-CMs based cardiac cell therapy for damaged heart.
Author Disclosures: S. funakoshi: None. K. Miki: None. T. Kimura: None. S. Yamanaka: Consultant/Advisory Board; Modest; iPierian, iPS Academia Japan, Megakaryon Corporation, and Healios K.K.. Y. Yoshida: None.
- © 2014 by American Heart Association, Inc.