Abstract 204: Temporal Assessment of Human iPSC-Derived Cardiomyocytes to Assess the Maturity for Cardiac Repair Applications

Abstract

Cardiovascular disease is the major cause of heart failure following myocardial infarction (MI), which leads to death in acute condition. In the recent year, stem cell therapy has shown a great potential to repair the damaged heart tissue following an MI. Both adult and embryonic stem cells (ES) have potential to repair and regenerate tissue to compensate cell death during MI. Apart from ethical concern, there are several advantages of using human iPSC cardiomyocytes (hiPSC-CMs) over human ES. Most important, the hiPSC-CMs provides autologous cells source which one side eliminate the possibility of cellular rejection while on the other side enhance the possibility of its survival in damaged cardiac tissue. However, the lack of maturity in hiPSC-CMs is a major challenge to replicate and/or replace the adult cardiomyocytes with mature cardiomyocytes at the site of MI. Temporal assessment of cardiac maturity markers and structural gene in hiPSC-CMs cultured in vitro for up to four weeks and comparison with non-failing human heart (NF). The wk-4 hiPSC-CMs has shown an increase in cardiac transcription factor (2-fold, NKX-2.5); Myosin genes (2-3 fold, MYH7, MYHL2); cardiac troponin-T (3-4 fold, TNNI3 and TNNT3); K + channel genes (20-fold, KCNJ2); Ca 2+ related genes (10-fold, CASQ2); Gap-junction genes (2-fold, GJA1) and Na + Channel gene (5-fold, SCN5A). Further, TEM showed that the myofibrils in the wk-4 cardiomyocytes were more compact, aligned and organized. The Z and I-band and specifically M-band were also prominent in the wk-4 sarcomeres. Furthermore, the maturity of hiPSC-CMs was compared with the NF human heart. This study showed a time-course assessment of cardiomyocytes morphology, structural and expression of cardiac maturity genes in hiPSC-CMs cultured for up to four weeks in vitro . Based on the study of the cardiac transcription factor, Na-K channel-related gene and TEM analysis, wk-4 cardiomyocytes showed more maturity than week-1 cardiomyocytes. Studies are ongoing to compare the contractility and action potential of hiPSC-CMs. Finally, the mature hiPSC-CMs will provide autologous cell source and have a significant impact on the functional outcome of patients with acute MI.