Induced Pluripotent Stem Cell–Based Treatment of Acquired Heart Block
The Battle for Tomorrow Has Begun!
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Electronic pacing devices are designed to maintain a normal heart rate and have been used for >50 years to correct bradycardias caused by atrioventricular node block or sinus node dysfunction. These electronic devices work very well but are limited by their high cost and limited battery life, as well as risks for generator/lead failure, infection, hemorrhage, and cardiac/pulmonary collapse.1 Biological pacing is an attractive concept because it avoids these limitations while providing hardware-free cardiac pacing. Early studies used virus-mediated somatic gene transfer to modify the electrophysiologic properties of quiescent atrial or ventricular cells with the intent of achieving spontaneous electric firing to maintain chronotropic competency. Of these, the 2 best known approaches focus on (1) inhibiting the chamber-specific inward rectifier K+ current, which normally keeps the resting membrane potential at a strongly hyperpolarized voltage to electrically stabilize membrane potentials2 or (2) introducing a pacemaker-specific hyperpolarization-activated cyclic nucleotide–gated channel that mediates the funny current (If), which is activated by hyperpolarization and mediates an inward current leading to diastolic depolarization and pacemaker activity.3 While these approaches successfully conferred pacemaker activity, genetically modified cells lack many other features of …