Pluripotent Stem Cells and Related Technologies for the Treatment of Cardiac Disorders

The ability to reprogram adult somatic cells into human induced pluripotent stem cells (hiPSCs) that could later be coaxed to differentiate into a variety of cell-lineages (including cardiomyocytes) opened new avenues for basic and translational cardiac research. Here we describe efforts from our laboratory in establishing and coaxing the cardiomyocyte differentiation of patient-specific hiPSCs lines. We also describe recent efforts to derive chamber-specific cardiomyocyte subtypes (atrial cells, ventricular cells, and SA node pacemaker cells) from human pluripotent stem cells (hPSC) using developmental-biology inspired differentiation systems. The potential applications of the iPSCs derived cardiomyocyte for cardiovascular regenerative medicine will be discussed, including the use of ventricular myocytes for infarct repair and of SA node like pacemaker cells for the treatment of bradyarrhythmias ("biological pacemaker"). Finally, our efforts in combining the hPSC-cardiovascular cell derivatives with extracellular matrix components to derive human engineered heart tissues (EHTs) will be discussed with an emphasis on its potential use for disease modeling, drug development, and regenerative medicine.