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 (INa), nifedipine, a blocker of L-type Ca2+ current (ICaL), and E4031, a blocker of the rapid component of delayed rectifier K+ current (IKr). 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 (IKs).CONCLUSION: In hiPSC-derived cardiomyocytes of cardiac origin, INa, ICaL, IKr, and IKs 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.
Human-induced pluripotent stem cell-derived cardiomyocytes from cardiac progenitor cells: effects of selective ion channel blockade / C. Altomare, E. Pianezzi, E. Cervio, S. Bolis, V. Biemmi, P. Benzoni, G.G. Camici, T. Moccetti, L. Barile, G. Vassalli. - In: EUROPACE. - ISSN 1532-2092. - 18:suppl. 4(2016), pp. iv67-iv76. ((Intervento presentato al 8. convegno TRM Forum on Computer Simulation and Experimental Assessment of Cardiac Function - Towards Integration of Cardiac Functions tenutosi a Lugano nel 2015 [10.1093/europace/euw352].
|Titolo:||Human-induced pluripotent stem cell-derived cardiomyocytes from cardiac progenitor cells: effects of selective ion channel blockade|
|Parole Chiave:||Arrhythmia; Cardiac progenitor cell; Cardiomyocyte; Induced pluripotent stem cell; Ion current|
|Settore Scientifico Disciplinare:||Settore BIO/09 - Fisiologia|
|Data di pubblicazione:||2016|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1093/europace/euw352|
|Appare nelle tipologie:||01 - Articolo su periodico|