Induced Polyploidy in iPSCs Generates Cardiomyocytes with 40% Stronger Contractions

Researchers used CRISPR-based genome doubling in human iPSCs followed by directed differentiation into cardiomyocytes. Contractile force was measured via traction force microscopy and calcium transient imaging on engineered heart tissues, showing a 40% increase in peak force and 25% faster relaxation kinetics compared with standard diploid cells. The mechanism appears linked to increased sarcomere density and mitochondrial content rather than simple cell size scaling. Prior work on polyploid hepatocytes and skeletal muscle suggested similar functional scaling, yet cardiac applications had remained unexplored due to concerns over cell-cycle exit. This approach could address the immaturity that limits current stem-cell-derived cardiomyocyte grafts, though translation requires addressing arrhythmia risk and immune compatibility. Next steps include large-animal engraftment studies to test integration and long-term stability before any human dosing.