Altered calcium handling and increased contraction force in human embryonic stem cell derived cardiomyocytes following short term dexamethasone exposure

Georgios Kosmidis, Milena Bellin, Marcelo C. Ribeiro, Berend Van Meer, Dorien Ward-Van Oostwaard, Robert Passier, Leon G.J. Tertoolen, Christine L. Mummery, Simona Casini

Research output: Contribution to journalArticleAcademicpeer-review

10 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)998-1005
Number of pages8
JournalBiochemical and biophysical research communications
Volume467
Issue number4
DOIs
Publication statusPublished - 27 Nov 2015

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Stem cells
Cardiac Myocytes
Dexamethasone
Glucocorticoids
Calcium
Pluripotent Stem Cells
Action Potentials
Heart Diseases
Human Embryonic Stem Cells
Pharmacology
Phenotype
Safety

Keywords

  • Calcium handling
  • Cardiomyocytes
  • Electrophysiology
  • Glucocorticoids
  • Human embryonic stem cells

Cite this

Kosmidis, Georgios ; Bellin, Milena ; Ribeiro, Marcelo C. ; Van Meer, Berend ; Ward-Van Oostwaard, Dorien ; Passier, Robert ; Tertoolen, Leon G.J. ; Mummery, Christine L. ; Casini, Simona. / Altered calcium handling and increased contraction force in human embryonic stem cell derived cardiomyocytes following short term dexamethasone exposure. In: Biochemical and biophysical research communications. 2015 ; Vol. 467, No. 4. pp. 998-1005.
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Altered calcium handling and increased contraction force in human embryonic stem cell derived cardiomyocytes following short term dexamethasone exposure. / Kosmidis, Georgios; Bellin, Milena; Ribeiro, Marcelo C.; Van Meer, Berend; Ward-Van Oostwaard, Dorien; Passier, Robert; Tertoolen, Leon G.J.; Mummery, Christine L.; Casini, Simona.

In: Biochemical and biophysical research communications, Vol. 467, No. 4, 27.11.2015, p. 998-1005.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Altered calcium handling and increased contraction force in human embryonic stem cell derived cardiomyocytes following short term dexamethasone exposure

AU - Kosmidis, Georgios

AU - Bellin, Milena

AU - Ribeiro, Marcelo C.

AU - Van Meer, Berend

AU - Ward-Van Oostwaard, Dorien

AU - Passier, Robert

AU - Tertoolen, Leon G.J.

AU - Mummery, Christine L.

AU - Casini, Simona

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AB - 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.

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KW - Electrophysiology

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