Human-induced pluripotent stem cell-derived cardiomyocytes from cardiac progenitor cells: effects of selective ion channel blockade

Aim Human-induced pluripotent stem cell (hiPSC)‐derived cardiomyocytes are likely to revolutionize electrophysiological approaches to arrhythmias. Recent evidence suggests the somatic cell origin of hiPSCs may influence their differentiation potential. Owing to their cardiomyogenic potential, cardiac-stromal progenitor cells (CPCs) are an interesting cellular source for generation of hiPSC‐derived cardiomyocytes. The effect of ionic current blockade in hiPSC‐derived cardiomyocytes generated from CPCs has not been characterized yet. Methods and results Human-induced pluripotent stem cell‐derived cardiomyocytes were generated from adult CPCs and skin fibroblasts from the same individuals. The effect of selective ionic current blockade on spontaneously beating hiPSC‐derived cardiomyocytes was assessed using multi-electrode arrays. Cardiac-stromal progenitor cells could be reprogrammed into hiPSCs, then differentiated into hiPSC‐derived cardiomyocytes. Human-induced pluripotent stem cell‐derived cardiomyocytes of cardiac origin showed higher upregulation of cardiac-specific genes compared with those of fibroblastic origin. Human-induced pluripotent stem cell‐derived cardiomyocytes of both somatic cell origins exhibited sensitivity to tetrodotoxin, a blocker of Na+ current ( I Na), nifedipine, a blocker of L-type Ca2+ current ( I CaL), and E4031, a blocker of the rapid component of delayed rectifier K+ current ( I Kr). Human-induced pluripotent stem cell‐derived cardiomyocytes of cardiac origin exhibited sensitivity to JNJ303, a blocker of the slow component of delayed rectifier K+ current ( I Ks). Conclusion In hiPSC‐derived cardiomyocytes of cardiac origin, I Na, I CaL, I Kr, and I Ks were present as tetrodotoxin-, nifedipine-, E4031-, and JNJ303-sensitive currents, respectively. Although cardiac differentiation efficiency was improved in hiPSCs of cardiac vs. non-cardiac origin, no major functional differences were observed between hiPSC‐derived cardiomyocytes of different somatic cell origins. Further studies are warranted to characterize electrophysiological properties of hiPSC‐derived cardiomyocytes generated from CPCs.