title: Human-induced pluripotent stem cell-derived cardiomyocytes from cardiac progenitor cells: effects of selective ion channel blockade.
abstract: OBJECTIVE
  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.
  
  
  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).
  
  
  CONCLUSIONS
  In hiPSC-derived cardiomyocytes of cardiac origin, INa, ICaL, IKr, and IKswere 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.
authors.affiliation: Cellular and Molecular Cardiology Laboratory, Swiss Institute for Regenerative Medicine (SIRM), 6807 Taverne Switzerland and Cardiocentro Ticino, 6900 Lugano, Switzerland.
authors.forename: Claudia
authors.initials: C
authors.lastname: Altomare
authors.affiliation: Cellular and Molecular Cardiology Laboratory, Swiss Institute for Regenerative Medicine (SIRM), 6807 Taverne Switzerland and Cardiocentro Ticino, 6900 Lugano, Switzerland.|Department of Molecular Cardiology, University of Zürich, 8001 Zürich, Switzerland.
authors.forename: Enea
authors.initials: E
authors.lastname: Pianezzi
authors.affiliation: Cellular and Molecular Cardiology Laboratory, Swiss Institute for Regenerative Medicine (SIRM), 6807 Taverne Switzerland and Cardiocentro Ticino, 6900 Lugano, Switzerland.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Cervio
authors.affiliation: Cellular and Molecular Cardiology Laboratory, Swiss Institute for Regenerative Medicine (SIRM), 6807 Taverne Switzerland and Cardiocentro Ticino, 6900 Lugano, Switzerland.
authors.forename: Sara
authors.initials: S
authors.lastname: Bolis
authors.affiliation: Cellular and Molecular Cardiology Laboratory, Swiss Institute for Regenerative Medicine (SIRM), 6807 Taverne Switzerland and Cardiocentro Ticino, 6900 Lugano, Switzerland.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Biemmi
authors.affiliation: Fibroblast Reprogramming Unit, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Benzoni
authors.affiliation: Department of Molecular Cardiology, University of Zürich, 8001 Zürich, Switzerland.
authors.forename: Giovanni G
authors.initials: GG
authors.lastname: Camici
authors.affiliation: Cellular and Molecular Cardiology Laboratory, Swiss Institute for Regenerative Medicine (SIRM), 6807 Taverne Switzerland and Cardiocentro Ticino, 6900 Lugano, Switzerland.
authors.forename: Tiziano
authors.initials: T
authors.lastname: Moccetti
authors.affiliation: Cellular and Molecular Cardiology Laboratory, Swiss Institute for Regenerative Medicine (SIRM), 6807 Taverne Switzerland and Cardiocentro Ticino, 6900 Lugano, Switzerland.
authors.forename: Lucio
authors.initials: L
authors.lastname: Barile
authors.affiliation: Cellular and Molecular Cardiology Laboratory, Swiss Institute for Regenerative Medicine (SIRM), 6807 Taverne Switzerland and Cardiocentro Ticino, 6900 Lugano, Switzerland.|Department of Cardiology, University of Lausanne Medical Center (CHUV), 1011 Lausanne, Switzerland.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Vassalli
mesh_terms: D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects* / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D065150:Cellular Reprogramming; D051668:Delayed Rectifier Potassium Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000187:drug effects* / Q000378:metabolism; D008564:Membrane Potentials; D049990:Membrane Transport Modulators / Q000494:pharmacology*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D010641:Phenotype; D026902:Potassium Channel Blockers / Q000494:pharmacology; D026941:Sodium Channel Blockers / Q000494:pharmacology; D015222:Sodium Channels / Q000187:drug effects* / Q000378:metabolism
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D051668:Delayed Rectifier Potassium Channels; D049990:Membrane Transport Modulators; D026902:Potassium Channel Blockers; D026941:Sodium Channel Blockers; D015222:Sodium Channels
keywords: Arrhythmia; Cardiac progenitor cell; Cardiomyocyte; Induced pluripotent stem cell; Ion current