Comparison of cultured human cardiomyocyte clusters obtained from embryos/fetuses or derived from human embryonic stem cells
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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Comparison of cultured human cardiomyocyte clusters obtained from embryos/fetuses or derived from human embryonic stem cells. / Grubb, Søren J; Vestergaard, Maj Linea; Andersen, Astrid Sten; Rasmussen, Karen Koefod; Mamsen, Linn; Tuckute, Greta; Grunnet-Lauridsen, Kristina; Møllgård, Kjeld; Ernst, Erik; Christensen, Søren T; Calloe, Kirstine; Andersen, Claus Yding.
I: Stem Cells and Development, Bind 28, Nr. 9, 2019, s. 608-619.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - Comparison of cultured human cardiomyocyte clusters obtained from embryos/fetuses or derived from human embryonic stem cells
AU - Grubb, Søren J
AU - Vestergaard, Maj Linea
AU - Andersen, Astrid Sten
AU - Rasmussen, Karen Koefod
AU - Mamsen, Linn
AU - Tuckute, Greta
AU - Grunnet-Lauridsen, Kristina
AU - Møllgård, Kjeld
AU - Ernst, Erik
AU - Christensen, Søren T
AU - Calloe, Kirstine
AU - Andersen, Claus Yding
PY - 2019
Y1 - 2019
N2 - Cardiomyocytes (CM) derived from human embryonic stem cells (hESC) or induced pluripotent stem cells (iPSC) are used to study cardiogenesis and mechanisms of heart disease and are advancing as a method for toxicological screening of drugs. The phenotype of stem cell-derived CMs should ideally resemble native CMs. Here we compare embryonic/fetal CMs with hESC-derived CMs according to function and morphology. CM clusters were obtained from human embryonic/fetal hearts from elective terminated pregnancies before gestational week 12 and separated into atrial and ventricular tissues. Specific markers for embryonic CMs and primary cilia were visualised using immunofluorescence microscopy analysis. Contracting hECM clusters morphologically and phenotypically resemble CMs in the embryonic/fetal heart. In addition, the contracting hECM clusters expressed primary cilia similar to that of cells in the embryonic/fetal heart. The electrophysiological characteristics of atrial and ventricular CMs were established by recording action potentials (AP) using sharp electrodes; In contrast to ventricular APs, atrial APs displayed a marked early repolarization followed by a plateau phase. hESC-CMs displayed a continuum of AP shapes. In all embryonic/fetal clusters, both atrial and ventricular, AP duration was prolonged by exposure to the KV11.1 channel inhibitor dofetilide (50 nM), however, the prolongation was not significant, possibly due to the relatively small number of experiments. This study provides novel information on APs and functional characteristics of atrial and ventricular CMs in first trimester hearts and demonstrates that Kv11.1 channels play a functional role already at these early stages. These results provide information needed to validate methods being developed on the basis of in vitro-derived CMs from either hESC or iPSC and although there was a good correlation between the morphology of the two types of CMs, differences in electrophysiological characteristics exist.
AB - Cardiomyocytes (CM) derived from human embryonic stem cells (hESC) or induced pluripotent stem cells (iPSC) are used to study cardiogenesis and mechanisms of heart disease and are advancing as a method for toxicological screening of drugs. The phenotype of stem cell-derived CMs should ideally resemble native CMs. Here we compare embryonic/fetal CMs with hESC-derived CMs according to function and morphology. CM clusters were obtained from human embryonic/fetal hearts from elective terminated pregnancies before gestational week 12 and separated into atrial and ventricular tissues. Specific markers for embryonic CMs and primary cilia were visualised using immunofluorescence microscopy analysis. Contracting hECM clusters morphologically and phenotypically resemble CMs in the embryonic/fetal heart. In addition, the contracting hECM clusters expressed primary cilia similar to that of cells in the embryonic/fetal heart. The electrophysiological characteristics of atrial and ventricular CMs were established by recording action potentials (AP) using sharp electrodes; In contrast to ventricular APs, atrial APs displayed a marked early repolarization followed by a plateau phase. hESC-CMs displayed a continuum of AP shapes. In all embryonic/fetal clusters, both atrial and ventricular, AP duration was prolonged by exposure to the KV11.1 channel inhibitor dofetilide (50 nM), however, the prolongation was not significant, possibly due to the relatively small number of experiments. This study provides novel information on APs and functional characteristics of atrial and ventricular CMs in first trimester hearts and demonstrates that Kv11.1 channels play a functional role already at these early stages. These results provide information needed to validate methods being developed on the basis of in vitro-derived CMs from either hESC or iPSC and although there was a good correlation between the morphology of the two types of CMs, differences in electrophysiological characteristics exist.
U2 - 10.1089/scd.2018.0231
DO - 10.1089/scd.2018.0231
M3 - Journal article
C2 - 30755084
VL - 28
SP - 608
EP - 619
JO - Stem Cells and Development
JF - Stem Cells and Development
SN - 1547-3287
IS - 9
ER -
ID: 213713131