title: Altered calcium handling and increased contraction force in human embryonic stem cell derived cardiomyocytes following short term dexamethasone exposure.
abstract: One limitation in using human pluripotent stem cell derived cardiomyocytes (hPSC-CMs) for disease modeling and cardiac safety pharmacology is their immature functional phenotype compared with adult cardiomyocytes. Here, we report that treatment of human embryonic stem cell derived cardiomyocytes (hESC-CMs) with dexamethasone, a synthetic glucocorticoid, activated glucocorticoid signaling which in turn improved their calcium handling properties and contractility. L-type calcium current and action potential properties were not affected by dexamethasone but significantly faster calcium decay, increased forces of contraction and sarcomeric lengths, were observed in hESC-CMs after dexamethasone exposure. Activating the glucocorticoid pathway can thus contribute to mediating hPSC-CMs maturation.
authors.affiliation: Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Georgios
authors.initials: G
authors.lastname: Kosmidis
authors.affiliation: Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Milena
authors.initials: M
authors.lastname: Bellin
authors.affiliation: Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Marcelo C
authors.initials: MC
authors.lastname: Ribeiro
authors.affiliation: Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Berend
authors.initials: B
authors.lastname: van Meer
authors.affiliation: Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Dorien
authors.initials: D
authors.lastname: Ward-van Oostwaard
authors.affiliation: Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands; MIRA, University of Twente, The Netherlands.
authors.forename: Robert
authors.initials: R
authors.lastname: Passier
authors.affiliation: Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Leon G J
authors.initials: LG
authors.lastname: Tertoolen
authors.affiliation: Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Christine L
authors.initials: CL
authors.lastname: Mummery
authors.affiliation: Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: s.casini@amc.uva.nl.
authors.forename: Simona
authors.initials: S
authors.lastname: Casini
mesh_terms: D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D003907:Dexamethasone / Q000378:metabolism / Q000494:pharmacology*; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D018398:Homeodomain Proteins; C491534:TLX2 protein, human; D003907:Dexamethasone; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D002118:Calcium
keywords: Calcium handling; Cardiomyocytes; Electrophysiology; Glucocorticoids; Human embryonic stem cells